Unraveling the role of Breg cells in digestive tract cancer and infectious immunity.

Over the past two decades, regulatory B cells (Breg cells or Bregs) have emerged as an immunosuppressive subset of B lymphocytes playing a key role in inflammation, infection, allergy, transplantation, and cancer. However, the involvement of Bregs in various pathological conditions of the gastrointestinal tract is not fully understood and is the subject of much recent research. In this review, we aimed to summarize the current state of knowledge about the origin, phenotype, and suppressive mechanisms of Bregs. The relationship between the host gut microbiota and the function of Bregs in the context of the disturbance of mucosal immune homeostasis is also discussed. Moreover, we focused our attention on the role of Bregs in certain diseases and pathological conditions related to the digestive tract, especially Helicobacter pylori infection, parasitic diseases (leishmaniasis and schistosomiasis), and gastrointestinal neoplasms. Increasing evidence points to a relationship between the presence and number of Bregs and the severity and progression of these pathologies. As the number of cases is increasing year by year, also among young people, it is extremely important to understand the role of these cells in the digestive tract.

Metformin - a new approach.

Metformin is a widely used biguanide drug recommended as a first-line antidiabetic for type 2 diabetes. Currently, metformin is used not only in the treatment of diabetes but also in other diseases. Some studies have shown that metformin causes weight loss in insulin-sensitive and insulin-resistant overweight and obese patients. Metformin is an effective and safe option for women with gestational diabetes and type 2 diabetes in pregnancy, and it may also increase the ovulation rate in patients with polycystic ovary syndrome (PCOS). Longer survival times have been observed in cancer patients using metformin. Metformin has been shown to significantly correlate with lower mortality in obese or type 2 diabetic women hospitalized for COVID-19. It also has a protective effect on the development and progression of many types of cancer. The mechanisms of action of metformin are complex and still not fully understood. Metformin has been shown to act through both AMP-activated protein kinase (AMPK)-dependent mechanisms and AMPK-independent mechanisms. This paper presents the benefits of using metformin in the treatment of various diseases.

Evaluation of Interactions of Selected Olivacine Derivatives with DNA and Topoisomerase II.

Olivacine and ellipticine are model anticancer drugs acting as topoisomerase II inhibitors. Here, we present investigations performed on four olivacine derivatives in light of their antitumor activity. The aim of this study was to identify the best antitumor compound among the four tested olivacine derivatives. The study was performed using CCRF/CEM and MCF-7 cell lines. Comet assay, polarography, inhibition of topoisomerase II activity, histone acetylation, and molecular docking studies were performed. Each tested compound displayed interaction with DNA and topoisomerase II, but did not cause histone acetylation. Compound 2 (9-methoxy-5,6-dimethyl-1-({[1-hydroxy-2-(hydroxymethyl)butan-2-yl]amino}methyl)-6H-pyrido[4,3-b]carbazole) was found to be the best candidate as an anticancer drug because it had the highest affinity for topoisomerase II and caused the least genotoxic damage in cells.

Are Biogenic and Pyrogenic Mesoporous SiO2 Nanoparticles Safe for Normal Cells?

Silicon dioxide, in the form of nanoparticles, possesses unique physicochemical properties (size, shape, and a large surface to volume ratio). Therefore, it is one of the most promising materials used in biomedicine. In this paper, we compare the biological effects of both mesoporous silica nanoparticles extracted from Urtica dioica L. and pyrogenic material. Both SEM and TEM investigations confirmed the size range of tested nanoparticles was between 6 and 20 nanometers and their amorphous structure. The cytotoxic activity of the compounds and intracellular ROS were determined in relation to cells HMEC-1 and erythrocytes. The cytotoxic effects of SiO2 NPs were determined after exposure to different concentrations and three periods of incubation. The same effects for endothelial cells were tested under the same range of concentrations but after 2 and 24 h of exposure to erythrocytes. The cell viability was measured using spectrophotometric and fluorimetric assays, and the impact of the nanoparticles on the level of intracellular ROS. The obtained results indicated that bioSiO2 NPs, present higher toxicity than pyrogenic NPs and have a higher influence on ROS production. Mesoporous silica nanoparticles show good hemocompatibility but after a 24 h incubation of erythrocytes with silica, the increase in hemolysis process, the decrease in osmotic resistance of red blood cells, and shape of erythrocytes changed were observed.

Calophyllum inophyllum in vaginitis treatment: Stimulated by electroporation with an in vitro approach.

BACKGROUND: Vaginitis is one of the most common problems in clinical medicine and is cited most often during visits to obstetricians and gynecologists. Most of the inflammation cases are caused by candidiasis trichomoniasis and bacterial vaginosis. Therefore, treatment of vaginal infections must use antibiotic or antifungal drugs, which often provide quick relief to the patient. The real cause of the problem - disrupting the ecosystem of the vagina - remains unchanged. Thus, new therapeutic compounds are being explored. OBJECTIVES: The aim of our study was to evaluate the effect of a natural substance: tamanu oil, an extract from the plant Calophyllum inophyllum, applied to the human fibroblast cell line (normal human dermal fibroblasts - NHDFs) and to the isolated human fibroblasts from the vagina (human vaginal fibroblasts - HVFs) in vitro. MATERIAL AND METHODS: We evaluated the viability of cells by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) assay after incubation only with tamanu oil and with electroporation (EP). We also examined the immunocytochemical reaction of collagen type III and mitochondrial superoxide dismutase (MnSOD) under established conditions. RESULTS: Tamanu oil increased the proliferation of cells and the amount of collagen III. It has been shown that the C. inophyllum extract stimulates the proliferation of commercial fibroblasts. For direct application in patients, one should use C. inophyllum extract in the range of 1:10-1:100 (saline dilution). CONCLUSIONS: The use of this extract (at concentrations indicated by the studies presented here) stimulates the healing processes (increased expression of collagen type III), and has anti-inflammatory, analgesic and antiseptic qualities.

Strontium-doped organic-inorganic hybrids towards three-dimensional scaffolds for osteogenic cells.

Biomimetic organic-inorganic hybrid bioscaffolds are developed to complement or replace damaged fragments in bone tissue surgery. The aim of this work was to develop a simple and fast method to prepare composite material for bone engineering, avoiding time consuming and complex methodologies. The resulting materials (also called in this work as hybrid composites or hybrid scaffolds) have a three-dimensional macroporous polymer-like network derived from triethoxyvinylsilane (TEVS) and 2-hydroxyethylmethacrylate (HEMA) monomers, with incorporated calcium, strontium, and phosphate ions. The materials were fully characterized using FT-IR, biomineralization studies, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy, scratch tests, Young's modulus and compressive strength tests, and gas physisorption. We report a comprehensive study on the in vitro effect of novel strontium doped materials on human bone cells. In vitro investigations were conducted using a normal human osteoblast cell line that mimics the cellular events of the in vivo intramembranous bone formation process. The materials do not have a negative impact on the survival of the normal human osteoblasts; moreover, materials doped with strontium show that not only are cells able to survive, but they also attach to and grow on a bioscaffolds surface. For this reason, they may be used in future in vivo experiments.

Expression of Metallothionein and Vascular Endothelial Growth Factor Isoforms in Breast Cancer Cells.

BACKGROUND: Metallothioneins (MTs) are low-molecular-weight and cysteine-rich proteins that bind heavy metal ions and oxygen-free radicals. MTs are commonly expressed in various tissues of mammals and are involved in regulation of cell proliferation and differentiation, and may be engaged in angiogenesis. Expression of MTs has been studied in many cancer types, especially breast cancer. The research results indicate that MTs may play important, although not yet fully known, roles in cancer angiogenesis. The aim of this study was to analyze the level of gene expression of selected MT isoforms induced with zinc ions in correlation with vascular endothelial growth factor (VEGF) isoforms in in vitro models of breast cancer. MATERIALS AND METHODS: The studies were carried out in three breast cancer cell lines (MCF-7, SK-BR-3, MDA-MB-231). An epithelial cell line derived from normal breast tissue (Me16c) was used as a control. The levels of expression of selected MT isoforms and selected genes involved in angiogenesis were studied with real-time PCR. RESULTS: Expression of different MT isoforms was induced by zinc ions to differing degrees in individual breast cancer cell lines. An increase in the expression of some MT isoforms was associated with a slight increase in the level of expression of VEGFA. CONCLUSION: The research results may indicate certain correlation between an increased expression of selected MT isoforms and a pro-angiogenic factor VEGF in specific types of breast cancer cells.

Influence of ezetimibe on ADMA-DDAH-NO pathway in rat liver subjected to partial ischemia followed by global reperfusion.

BACKGROUND: We evaluated effect of ezetimibe on selected parameters determining NO level in rat liver subjected to ischemia reperfusion (IR). METHODS: Rats received ezetimibe (5 mg/kg) (groups E0 and EIR) or saline solution (groups C0 and CIR) intragastrically for 21 days. Then, the livers of CIR and EIR underwent ischemia (60 min) and reperfusion (4 h). Blood samples were obtained before surgery to estimate activities of aminotransferases, and just before ischemia and during reperfusion to estimate asymmetric and symmetric dimethylarginine (ADMA, SDMA) and arginine (Arg) levels. After IR, dimethylarginine dimethylaminohydrolase (DDAH) activity and endothelial nitric oxide synthase (eNOS) protein concentration were measured in liver homogenates. DDAH and protein arginine methyltransferase (PRMT) mRNA were quantified by real-time PCR in liver tissue samples. RESULTS: In CIR, the ADMA level was significantly higher compared to all other groups in 30 min and to E0 group in 120 min of reperfusion. In EIR, ADMA was low, compared to non-ischemic groups. At 30 and 120 min of reperfusion, in non-ischemic groups the level of Arg and Arg/ADMA ratio were significantly higher than in ischemic groups and E0 was the group with the highest levels of those parameters of all. In CIR, eNOS protein concentration was significantly lower than in ezetimibe-treated groups. Activity of DDAH was significantly higher in E0 than in non-treated groups. In ischemic groups, DDAH mRNA expression was significantly higher than in non-ischemic ones and PRMT mRNA expression was significantly higher in C0 than in all other groups. CONCLUSIONS: Influence of ezetimibe on ADMA/DDAH/NO pathway demonstrated in this work may suggest protective properties of this drug on rat livers injured by IR and, to a lower extent, on livers non-subjected to IR.

Non-cytotoxic organic-inorganic hybrid bioscaffolds: An efficient bedding for rapid growth of bone-like apatite and cell proliferation.

Synthesis and characterization of organic-inorganic macroporous hybrid scaffolds were investigated. The materials were prepared by combining 2-hydroxyethylmethacrylate (HEMA) and triethoxyvinylsilane (TEVS) chemically modified by Ca2+ and PO43- ions via sol-gel route. In this study we have constructed a sugar-based cracks-free three-dimensional (3D) network with interconnected porous architecture within the range of 150-300µm and rough topography. The obtained results revealed that both topography and composition of prepared materials allow rapid growth of the bone-like apatite (HAp) layer on their surface after soaking in biological medium. Preliminary studies have shown that hybrids covered by HAp are non-cytotoxic and allow cell proliferation that make them a promising scaffolds in the field of bone regenerative medicine. The materials were mainly characterized by powder X-ray diffraction analysis (PXRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy-energy-dispersive spectroscopy (SEM-EDS) and transmission electron microscopy-energy-dispersive spectroscopy (TEM-EDS).