In vivo testing of a bioresorbable phosphate-based optical fiber.

Optical fibers have recently attracted a noticeable interest for biomedical applications because they provide a minimally invasive method for in vivo sensing, imaging techniques, deep-tissue photodynamic therapy or optogenetics. The silica optical fibers are the most commonly used because they offer excellent optical properties, and they are readily available at a reasonable price. The fused silica is a biocompatible material, but it is not bioresorbable so it does not decompose in the body and the fibers must be ex-planted after in vivo use and their fragments can present a considerable risk to the patient when the fiber breaks. In contrast, optical fibers made of phosphate glasses can bring many benefits because such glasses exhibit good transparency in ultraviolet-visible and near-infrared regions, and their solubility in water can be tailored by changing the chemical composition. The bioresorbability and toxicity of phosphate glass-based optical fibers were tested in vivo on male laboratory rats for the first time. The fiber was spliced together with a standard graded-index multi-mode fiber pigtail and an optical probe for in vitro pH measurement was prepared by the immobilization of a fluorescent dye on the fiber tip by a sol-gel method to demonstrate applicability and compatibility of the fiber with common fiber optics.

Distribution of metastases in mesorectum is unpredictable: Metastases do not respect tumor localization even in small non-circumferential rectal cancers.

INTRODUCTION: Low anterior resection with total mesorectal excision (TME) is the gold standard for surgical treatment of rectal carcinoma. The radicality of this procedure is negatively counterbalanced by morbidity, lethality, and numerous other complications. Local excision would appear to be an attractive alternative, but its radicality is disputable due to risk of undetected metastasis to the mesorectum. The study aimed to determine the location of mesorectal metastases with respect to circumferentially - located tumors in patients with tumors involving less than one-third of the rectal circumference. MATERIALS AND METHODS: Resected specimens from patients with tumors smaller than one-third of the circumference were divided into: Sector A - tumorous, and Sector B - nontumorous. Group A was created by the pathologist cutting part of the rectal wall with the adjacent mesorectum, as though imitating a full-thickness excision. RESULTS: The study comprised 35 patients with a mean age of 66 years, of which 23 were men (65.7%) and 12 were women (34.2%). Tumors were predominantly (y)pT1-T2; a total of 799 lymph nodes and 5 tumor satellites were examined. Six patients (17.1%) were identified as stage (y)pN+. A total of 3 positive findings (lymph node metastasis or satellites) were detected in 3 patients (8.5%) in tumorous Sector A; and 8 positive findings were detected in 4 patients (11.4%) in non-tumorous Sector B. CONCLUSION: Rectal carcinoma involving one-third of the rectal circumference metastasizes discontinuously, and spreads into parts of the mesorectum beyond the tumor area.

Flavonoid 4'-O-Methylkuwanon E from Morus alba Induces the Differentiation of THP-1 Human Leukemia Cells.

Aims. In this work we studied cytodifferentiation effects of newly characterized prenyl flavonoid 4'-O-methylkuwanon E (4ME) isolated from white mulberry (Morus alba L.). Main Methods. Cell growth and viability were measured by dye exclusion assay; cell cycle and surface antigen CD11b were monitored by flow cytometry. For the cytodifferentiation of cells the NBT reduction assay was employed. Regulatory proteins were assessed by western blotting. Key Findings. 4ME induced dose-dependent growth inhibition of THP-1 cells, which was not accompanied by toxic effect. Inhibition of cells proliferation caused by 4ME was associated with the accumulation in G1 phase and with downregulation of hyperphosphorylated pRb. Treatment with 4ME led to significant induction of NBT-reducing activity of PMA stimulated THP-1 cells and upregulation expression of differentiation-associated surface antigen CD11b. Our results suggest that monocytic differentiation induced by 4ME is connected with up-regulation of p38 kinase activity. Significance. Our study provides the first evidence that 4ME induces the differentiation of THP-1 human monocytic leukemia cells and thus is a potential cytodifferentiating anticancer agent.

Prenylated Flavonoids from Morus alba L. Cause Inhibition of G1/S Transition in THP-1 Human Leukemia Cells and Prevent the Lipopolysaccharide-Induced Inflammatory Response.

Morus alba L. (MA) is a natural source of many compounds with different biological effects. It has been described to possess anti-inflammatory, antioxidant, and hepatoprotective activities. The aim of this study was to evaluate cytotoxicity of three flavonoids isolated from MA (kuwanon E, cudraflavone B, and 4'-O-methylkuwanon E) and to determine their effects on proliferation of THP-1 cells, and on cell cycle progression of cancer cells. Anti-inflammatory effects were also determined for all three given flavonoids. Methods used in the study included quantification of cells by hemocytometer and WST-1 assays, flow cytometry, western blotting, ELISA, and zymography. From the three compounds tested, cudraflavone B showed the strongest effects on cell cycle progression and viability of tumor and/or immortalized cells and also on inflammatory response of macrophage-like cells. Kuwanon E and 4'-O-methylkuwanon E exerted more sophisticated rather than direct toxic effect on used cell types. Our data indicate that mechanisms different from stress-related or apoptotic signaling pathways are involved in the action of these compounds. Although further studies are required to precisely define the mechanisms of MA flavonoid action in human cancer and macrophage-like cells, here we demonstrate their effects combining antiproliferative and anti-inflammatory activities, respectively.

Cytotoxicity and effects on inflammatory response of modified types of cellulose in macrophage-like THP-1 cells.

The cytotoxicity and in vitro effects of six variously modified types of cellulose (OC--oxidized cellulose, NaOC--oxidized cellulose sodium salt, DAC--dialdehyde cellulose, CMC--carboxymethyl cellulose, MFC--microfibrilated cellulose, and MCC--microcrystalline cellulose) on the inflammatory response in macrophage-like THP-1 cells were examined, with special focus on their ability to influence gene expression and the production of TNF-α. The study provides evidence that DAC exerts a marked effect on the induction of TNF-α gene expression and its subsequent production in human macrophages. Thus, the use of DAC for anti-hemorrhagic or wound-healing therapy should be considered carefully with regard to its pro-inflammatory activity. On the contrary, MCC showed significant anti-inflammatory effects in the LPS-induced conditions, which might be beneficial for the treatment of non-healing chronic wounds, e.g., diabetic or venous ulcers.

Natural compound cudraflavone B shows promising anti-inflammatory properties in vitro.

Cudraflavone B (1) is a prenylated flavonoid found in large amounts in the roots of Morus alba, a plant used as a herbal remedy for its reputed anti-inflammatory properties. The present study shows that this compound causes a significant inhibition of inflammatory mediators in selected in vitro models. Thus, 1 was identified as a potent inhibitor of tumor necrosis factor α (TNFα) gene expression and secretion by blocking the translocation of nuclear factor κB (NF-κB) from the cytoplasm to the nucleus in macrophages derived from a THP-1 human monocyte cell line. The NF-κB activity reduction resulted in the inhibition of cyclooxygenase 2 (COX-2) gene expression. Compound 1 acts as a COX-2 and COX-1 inhibitor with higher selectivity toward COX-2 than indomethacin. Pretreatment of cells by 1 shifted the peak in an regulatory gene zinc-finger protein 36 (ZFP36) expression assay. This natural product has noticeable anti-inflammatory properties, suggesting that 1 potentially could be used for development as a nonsteroidal anti-inflammatory drug lead.

Geranylated flavanone tomentodiplacone B inhibits proliferation of human monocytic leukaemia (THP-1) cells.

BACKGROUND AND PURPOSE: Paulownia tomentosa is a rich source of geranylated flavanones, some of which we have previously shown to have cytotoxic activity. To identify members of this class of compounds with cytostatic effects, we assessed the effects of the geranylated flavanone tomentodiplacone B (TOM B) on cell cycle progression and cell cycle regulatory pathways of THP-1 human monocytic leukaemia cells. EXPERIMENTAL APPROACH: Cell viability was measured by dye exclusion and proliferation by WST-1 assays; cell cycle was monitored by flow cytometry. Regulatory proteins were assessed by immunoprecipitation and kinase assays, and Western blotting. KEY RESULTS: Tomentodiplacone B had no effect during the first 24 h of cell growth at concentrations between 1 and 2.5 µM, but inhibited cell growth in a dose-dependent manner at concentrations of 5 µM or higher. Growth inhibition during the first 24 h of exposure to TOM B was not accompanied by cytotoxicity as cells were accumulated in G1 phase dose-dependently. This G1 phase accumulation was associated with down-regulation of cyclin-dependent kinase 2 activity and also protein levels of cyclins E1 and A2. However, key stress-related molecules (γ-H2AX, p53 and p21) were not induced, suggesting that TOM B acts by directly inhibiting the cyclin-dependent kinase 2 signalling pathway rather than initiating DNA damage or cellular stress. CONCLUSIONS AND IMPLICATIONS: Our study provides the first evidence that TOM B directly inhibits proliferation of human monocytic leukaemia cells, and thus is a potential anticancer agent, preventing leukaemia cells from progressing from G1 phase into DNA synthesis.

Cytotoxic activities of several geranyl-substituted flavanones.

Nine geranylated flavanones isolated from the fruits of Paulownia tomentosa (4-12) and two from the roots of Morus alba (13 and 14) were examined for cytotoxicity to selected human cancer cell lines and normal human fibroblasts. Cytotoxicity was determined in vitro using a calcein AM cytotoxicity assay. Cytotoxicity for the THP-1 monocytic leukemia cell line was tested using erythrosin B cell staining. The geranylated compounds tested were compared with the known simple flavanone standards taxifolin (1), naringenin (2), and hesperetin (3) and with the standard anticancer drugs olomoucine II, diaziquone, and oxaliplatin and the antineoplastic compound camptothecin, and showed different levels of cytotoxicity. The effects of structural changes on cytotoxic activity, including geranyl substitution of the flavanone skeleton and the oxidation pattern of ring B of the flavanones, are discussed.

Effect of solvent on cytotoxicity and bioavailability of fatty acids.

Fatty acids (FAs) represent an important part of cell membranes and a source of energy. However, their abundance is linked with several diseases such as type 2 diabetes mellitus, and for this reason they are studied intensively. In this article we compare the two main methods of dissolving FAs for work in vitro, (i) dissolution in dimethylsulfoxide (DMSO) and (ii) conjugation with bovine serum albumin (BSA), and describe the effects of the solvent on cytotoxicity (determination of viability) and bioavailability (as shown by the impact on the gene expression of TNF-alpha). We have found that conjugation with BSA is significantly less cytotoxic than dissolution in DMSO and also yields greater bioavailability.