Biologically Active Ajuga Species Extracts Modulate Supportive Processes for Cancer Cell Development

Backround:Ajuga species have been used in traditional medicine for their diuretic, anti-inflammatory, wound-healing, and hepatoprotective properties.Purpose: The phytochemical profile and anticancer potential of three Ajuga sp. (A. genevensis, A. chamaepitys, and A. laxmannii) from Romania was investigated.Materials and Methods: The phytochemicals were extracted from the aerial parts of Ajuga sp. by using different solvents and methods. The hydroalcoholic extracts were examined for total phenolic, flavonoid and iridoid contents, and HPLC/MS was used to analyze the polyphenolic compounds and iridoids. The phytochemical profile was also evaluated by principal component analysis in connection with antitumor efficacy of extracts. The antiproliferative potential was evaluated using the ELISA BrdU-colorimetric immunoassay. Western Blot with regard to inflammatory protein NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) p65 subunit expression in cell lysates was performed. Quantification of oxidative stress marker malondialdehyde (MDA) was determined by high-performance liquid chromatography (HPLC). Enzymatic and non-enzymatic antioxidant capability was assessed by measuring catalase activity and by evaluating the total antioxidant capacity (TAC) of treated cells.Results:Ajuga laxmannii ethanol extract showed the highest total phenolic and flavonoid content, while A. genevensis ethanol extract was more abundant in iridoids. The overall cytostatic effect of the investigated plant extracts was exerted through strong inhibitory actions on NF-κB, the key molecule involved in the inflammatory response and via oxidative stress modulatory effects in both murine colon carcinoma and melanoma cell lines.Conclusion:Ajuga laxmannii showed the most significant antitumor activity and represents an important source of bioactive compounds, possibly an additional form of treatment alongside conventional anticancer drugs

No evidence for parasitism-linked changes in immune function or oxidative physiology over the annual cycle of an avian species

Temporally changing environmental conditions occur in most parts of the world and can exert strong pressure on the immune defense of organisms. Seasonality may result in changes in physiological traits over the year, and such changes may be essential for the optimization of defense against infections. Evidence from field and laboratory studies suggest the existence of links between environmental conditions, such as infection risk, and the ability of animals to mount an immune response or to overcome infections; however, the importance of parasites in mediating seasonal change in immune defense is still debated. In this study, we test the hypothesis that seasonal change in immune function and connected physiological traits is related to parasite infection. We sampled captive house sparrows (Passer domesticus) once every 2 mo over 14 mo and compared the annual variation in 12 measures of condition, immune function, antioxidant status, and oxidative damage among birds naturally infested with coccidians or medicated against these parasites. We found significant variation in 10 of 12 traits over the year. However, we found little support for parasite-mediated change in immune function and oxidative status in captive house sparrows. Of the 12 measures, only one was slightly affected by parasite treatment. In support of the absence of any effect of coccidians on the annual profile of the condition and physiological traits, we found no consistent relationships between the intensity of infestation and these response variables over the year. Our results show that chronic coccidian infections have limited effect on the seasonal changing of physiological traits and that the patterns of these measures are probably more affected by acute infection and/or virulent parasite strains

Seasonal Patterns and Relationships among Coccidian Infestations, Measures of Oxidative Physiology, and Immune Function in Free-Living House Sparrows over an Annual Cycle

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Seasonal patterns and relationships among coccidian infestations, measures of oxidative physiology, and immune function in free-living house sparrows over an annual cycle

Temporal variation in oxidative physiology and its associated immune function may occur as a result of changes in parasite infection over the year. Evidence from field and laboratory studies suggests links between infection risk, oxidative stress, and the ability of animals to mount an immune response; however, the importance of parasites in mediating seasonal change in physiological makeup is still debated. Also, little is known about the temporal consistency of relationships among parasite infestation, markers of oxidative status and immune function in wild animals, and whether variation in oxidative measures can be viewed as a single integrated system. To address these questions, we sampled free-living house sparrows (Passer domesticus) every 2 mo over a complete year and measured infestation with coccidian parasites as well as nine traits that reflect condition, oxidative physiology, and immune function. We found significant seasonal variation in coccidian infestation and in seven out of nine condition and physiological variables over the year. However, we found little support for parasite-mediated change in condition, oxidative physiology, and immune functions in house sparrows. In accordance with this, we found no temporal consistency in relationships between the intensity of infestation and physiology. Among measures of oxidative physiology, antioxidants (measured as the total antioxidant capacity and the concentration of uric acid in the plasma) and oxidative damage (measured through the level of malondialdehyde in plasma) positively and consistently covaried over the year, while no such associations were found for the rest of traits (body mass, total glutathione, and leukocyte numbers). Our results show that natural levels of chronic coccidian infection have a limited effect on the seasonal change of physiological traits, suggesting that the variation of the latter is probably more affected by short-term disturbances, such as acute infection and/or season-specific stress stimuli

Investigation into the Role of Tumor-Associated Macrophages in the Antitumor Activity of Doxil

Purpose. Our recent studies show specific localization of long-circulating liposomes (LCL) within the endosomal/lysosomal compartment of tumor-associated macrophages (TAM). Based on this finding, the present study aims to investigate whether clinically applied LCL formulations such as Doxil (LCLencapsulated doxorubicin), have alternative mechanisms of action additionally to direct drug-mediated cytotoxicity towards tumor cells. Methods. The antitumor activity of Doxil was evaluated in B16.F10 melanoma-bearing mice, in the presence and in the absence of TAM. To suppress TAM functions, liposomal clodronate (Lip-CLOD) was injected 24 h before the actual treatment. The effect of Doxil on the levels of angiogenic factors was determined using an angiogenic protein array. As positive control, the same experiments were conducted with LCL-encapsulated prednisolone phosphate (LCL-PLP), a tumor-targeted formulation with known strong anti-angiogenic/anti-inflammatory effects on TAM. Results. Our results show that the antitumor efficacy of Doxil was only partially attributed to the inhibition of TAM-mediated angiogenesis whereas LCL-PLP inhibited tumor growth through strong suppressive effects on pro-angiogenic functions of TAM. As described previously, the main mechanism of Doxil might be a cytotoxic effect on tumor cells. Conclusions. Our findings suggest that the antitumor activity of Doxil does not depend mainly on the presence of functional TAM in tumors

Antitumor Activity of Liposomal Prednisolone Phosphate Depends on the Presence of Functional Tumor-Associated Macrophages in Tumor Tissue1

Prednisolone phosphate (PLP) encapsulated in long-circulating liposomes (LCLs) (LCL-PLP) exerts antitumor activity through the inhibition of tumor angiogenesis. It is known that tumor-associated macrophages (TAMs) play a crucial role in tumor growth as they are actively involved in promoting and maintaining tumor angiogenesis. To gain more insight into the antiangiogenic mechanisms of LCL-PLP, this study aimed to investigate the role of TAM in the antitumor mode of action of LCL-PLP in B16.F10 melanoma-bearing mice. Our results show that TAMs have a pivotal function in the growth of B16.F10 melanoma through the production of pro-angiogenic/pro-inflammatory factors. One of the major inhibitory actions of LCL-PLP on tumor growth is the reduction of the TAM-mediated production of pro-angiogenic factors, whereas production of anti-angiogenic factors by these cells is hardly affected

Assessing the Efficiency of Triangular Gold Nanoparticles as NIR Photothermal Agents In Vitro and Melanoma Tumor Model

Photothermal therapy (PTT) is gaining a lot of interest as a cancer treatment option with minimal side effects due to the efficient photothermal agents employed. They are based on nanomaterials that, upon laser irradiation, absorb photon energy and convert it into heat to induce hyperthermia, which destroys the cancer cells. Here, the unique light-to-heat conversion features of three different gold nanotriangular nanoparticles (AuNTs) are evaluated with respect to their absorption properties to select the most efficient nanoheater with the highest potential to operate as an efficient photothermal agent. AuNTs with LSPR response in- and out- of resonance with the 785 nm near-infrared (NIR) excitation wavelength are investigated. Upon 15 min laser exposure, the AuNTs that exhibit a plasmonic response in resonance with the 785 nm laser line show the highest photothermal conversion efficacy of 80%, which correlates with a temperature increase of 22 °C. These photothermal properties are well-preserved in agarose-based skin biological phantoms that mimic the melanoma tumoral tissue and surrounding healthy tissue. Finally, in vitro studies on B16.F10 melanoma cells prove by fluorescence staining and MTT assay that the highest phototoxic effect after NIR laser exposure is induced by AuNTs with LSPR response in resonance with the employed laser line, thus demonstrating their potential implementation as efficient photothermal agents in PTT

Fecal Microbiota Transplant in Severe and Non-Severe <i>Clostridioides difficile</i> Infection. Is There a Role of FMT in Primary Severe CDI?

Background: Faecal microbiota transplant (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection (rCDI) with cure rates ranging between 85 and 92%. The FMT role for primary Clostridioides difficile infection (CDI) has yet to be settled because of limited data and small-sample studies presented in the current literature. Our study goals were to report the risk factors and the risk of recurrence after FMT for each CDI episode (first, second, and third) and to explore if there is a role of FMT in primary severe CDI. Methods: We conducted a retrospective study to analyze the clinical characteristics and the outcomes of 96 FMT patients with a prior 10 day course of antibiotic treatment in the medical records, of which 71 patients with recurrent CDI and 25 patients with a primary CDI. Results: The overall primary cure rate in our study was 88.5% and the primary cure rate for the severe forms was 85.7%. The data analysis revealed 5.25%, 15.15%, and 27.3% FMT recurrence rates for primary, secondary, and tertiary severe CDI. The risk of recurrence was significantly associated with FMT after the second and the third CDI severe episodes (p < 0.05), but not with FMT after the first severe CDI episode. Conclusions: This study brings new data in supporting the FMT role in CDI treatment, including the primary severe CDI, however, further prospective and controlled studies on larger cohorts should be performed in this respect