Assessment of the immunomodulatory properties of the probiotic strain Lactobacillus paracasei K5 in vitro and in vivo

Lactobacillus paracasei K5 is a lactic acid bacteria (LAB) strain that has been isolated from dairy products. Previous studies have established its probiotic potential in a series of in vitro tests, including molecular characterization, safety profiling, and tolerability of the gastrointestinal tract conditions. To characterize its beneficial actions on the host, we have shown previously that L. paracasei K5 adheres to Caco-2 cells and exerts anti-proliferative effects through the induction of apoptosis. In the present study, we focused on the immunomodulatory potential of this strain. We employed the dorsal-air-pouch mouse model of inflammation and recorded an eight-fold increase in the recruitment of immune cells in mice treated with the probiotic strain, compared to the control group. Analysis of the exudates revealed significant changes in the expression of pro-inflammatory mediators on site. Treatment of Caco-2 cells with L. paracasei K5 induced significant upregulation of cytokines interleukin-1α (IL-1α), ΙL-1β, IL-6, tumor necrosis factor-alpha (TNF-α), the chemokine C-X-C motif ligand 2 (CXCL2), and the inflammation markers soluble intercellular adhesion molecule (sICAM) and metallopeptidase inhibitor-1 (TIMP-1). Transient induction of the Toll-like receptors (TLRs) 2, 4, 6, and 9 expression levels was recorded by real-time PCR analysis. These results highlight the immunomodulatory potential of this strain and further support its probiotic character

Hyperthermia Suppresses Post - In Vitro Proliferation and Tumor Growth in Murine Malignant Melanoma and Colon Carcinoma

Background: Several studies have highlighted hyperthermia’s ability to enhance the effectiveness of radiation and chemotherapy in various in vitro and in vivo cancer models. Materials and Methods: In vivo murine models of malignant melanoma and colon carcinoma were utilized for demonstrating hyperthermia’s therapeutic effectiveness by examining levels of caspase 3, COX-2 and phospho-H2A.X (Ser139) as endpoints of apoptosis, proliferation and DNA damage respectively. Results: Hyperthermia induced in vitro cytotoxicity in malignant melanoma (B16-F10) and colon carcinoma (CT26) cell lines. In addition, it reduced post-in vitro proliferation and suppression of tumor growth by inducing the expression of caspase-3 and phospho-H2A.X (Ser139) while reducing the expression of COX-2 in both murine cancer models. Conclusion: Hyperthermia can exert therapeutic effectiveness against melanoma and colon carcinoma by inhibiting a number of critical cellular cascades including apoptosis, proliferation and DNA damage

Maximum inspiratory pressure, a surrogate parameter for the assessment of ICU-acquired weakness

<p>Abstract</p> <p>Background</p> <p>Physical examination has been advocated as a primary determinant of ICU-acquired weakness (ICU-AW). The purpose of the study is to investigate ICU-AW development by using Maximum Inspiratory Pressure (MIP) as a surrogate parameter of the standardized method to evaluate patients' peripheral muscle strength.</p> <p>Methods</p> <p>Seventy-four patients were recruited in the study and prospectively evaluated in a multidisciplinary university ICU towards the appearance of ICU-AW. APACHE II admission score was 16 ± 6 and ICU stay 26 ± 18 days. ICU-AW was diagnosed with the Medical Research Council (MRC) scale for the clinical evaluation of muscle strength. MIP was measured using the unidirectional valve method, independently of the patients' ability to cooperate.</p> <p>Results</p> <p>A significant correlation was found between MIP and MRC (r = 0.68, p < 0.001). Patients that developed ICU-AW (MRC<48) had a longer weaning period compared to non ICU-AW patients (12 ± 14 versus 2 ± 3 days, p < 0.01). A cut-off point of 36 cmH₂O for MIP was defined by ROC curve analysis for ICU-AW diagnosis (88% sensitivity,76% specificity). Patients with MIP below the cut-off point of 36 cmH₂O had a significant greater weaning period (10 ± 14 versus 3 ± 3 days, p = 0.004) also shown by Kaplan-Meier analysis (log-rank:8.2;p = 0.004).</p> <p>Conclusions</p> <p>MIP estimated using the unidirectional valve method may be a potential surrogate parameter for the assessment of muscle strength compromise, useful for the early detection of ICU-AW.</p

Dietary mastic oil extracted from Pistacia lentiscus var. chia suppresses tumor growth in experimental colon cancer models

Plant-derived bioactive compounds attract considerable interest as potential chemopreventive anticancer agents. We analyzed the volatile dietary phytochemicals (terpenes) present in mastic oil extracted from the resin of Pistacia lentiscus var. chia and comparatively investigated their effects on colon carcinoma proliferation, a) in vitro against colon cancer cell lines and b) in vivo on tumor growth in mice following oral administration. Mastic oil inhibited - more effectively than its major constituentsproliferation of colon cancer cells in vitro, attenuated migration and downregulated transcriptional expression of survivin (BIRC5a). When administered orally, mastic oil inhibited the growth of colon carcinoma tumors in mice. A reduced expression of Ki-67 and survivin in tumor tissues accompanied the observed effects. Notably, only mastic oil -which is comprised of 67.7% α-pinene and 18.8% myrceneinduced a statistically significant anti-tumor effect in mice but not α-pinene, myrcene or a combination thereof. Thus, mastic oil, as a combination of terpenes, exerts growth inhibitory effects against colon carcinoma, suggesting a nutraceutical potential in the fight against colon cancer. To our knowledge, this is the first report showing that orally administered mastic oil induces tumor-suppressing effects against experimental colon cancer

Evaluation of Antioxidant and Antiproliferative Properties of Cornus mas L. Fruit Juice

Cornus mas L. (Cornelian cherry) is a flowering plant indigenous to Europe and parts of Asia, mostly studied for the antimicrobial activity of its juice. In this report, we investigated the composition and the in vitro antioxidant capacity of Cornus mas L. fruit juice from Greece, as well as its antiproliferative properties in vitro and in vivo. The fruits showed a high content of citric, malic, and succinic acid, in contrast to their juice, which had a low concentration of organic acids. The juice demonstrated significant antioxidant activity against the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) and modest antiproliferative potential against four human cancer cells lines and one murine: mammary adenocarcinoma MCF-7, hepatocellular carcinoma HepG2 and colon adenocarcinomas Caco2, HT-29, as well as murine colon carcinoma CT26. Cell viability was reduced by 40&ndash;50% following incubation of the cells with the highest concentration of the juice. Although Cornelian cherry juice exhibited in vitro growth inhibitory effects against colon carcinoma cells, no tumor growth inhibition was observed in an in vivo experimental colon carcinoma model in mice following prophylactic oral administration of a daily dose of 100 &mu;L juice for a period of 10 days. Thus, our findings raise interesting questions for further research on Cornus mas L. fruit juice, and in parallel, the strong antioxidant potential implies that the plant could be further explored and exploited for its protective effect against oxidative damage

Nueva Alcarria: Año XXXI Número 1642 - 1970 mayo 23

In the present study, we have aimed to characterize the intrinsic, extrinsic and ER-mediated apoptotic induction by hyperthermia in an in vitro model of human malignant melanoma and furthermore, to evaluate its therapeutic effectiveness in an adjuvant therapeutic setting characterized by combinational treatments with non-targeted (Dacarbazine & Temozolomide) and targeted (Dabrafenib & Vemurafenib) drugs. Overall, our data showed that both low (43 °C) and high (45 °C) hyperthermic exposures were capable of inducing cell death by activating all apoptotic pathways but in a rather distinct manner. More specifically, low hyperthermia induced extrinsic and intrinsic apoptotic pathways both of which activated caspase 6 only as opposed to high hyperthermia which was mediated by the combined effects of caspases 3, 7 and 6. Furthermore, significant involvement of the ER was evident (under both hyperthermic conditions) suggesting its role in regulating apoptosis via activation of CHOP. Our data revealed that while low hyperthermia activated IRE-1 and ATF6 only, high hyperthermia induced activation of PERK as well suggesting that ultimately these ER stress sensors can lead to the induction of CHOP via different pathways of transmitted signals. Finally, combinational treatment protocols revealed an effect of hyperthermia in potentiating the therapeutic effectiveness of non-targeted as well as targeted drugs utilized in the clinical setting. Overall, our findings support evidence into hyperthermia’s therapeutic potential in treating human malignant melanoma by elucidating the underlying mechanisms of its complex apoptotic induction

Epidemiology of Candidemia and Fluconazole Resistance in an ICU before and during the COVID-19 Pandemic Era

The objectives of this study were to investigate the incidence of candidemia, as well as the factors associated with Candida species distribution and fluconazole resistance, among patients admitted to the intensive care unit (ICU) during the COVID-19 pandemic, as compared to two pre-pandemic periods. All patients admitted to the ICU due to COVID-19 from March 2020 to October 2021, as well as during two pre-pandemic periods (2005&ndash;2008 and 2012&ndash;2015), who developed candidemia, were included. During the COVID-19 study period, the incidence of candidemia was 10.2%, significantly higher compared with 3.2% and 4.2% in the two pre-pandemic periods, respectively. The proportion of non-albicans Candida species increased (from 60.6% to 62.3% and 75.8%, respectively), with a predominance of C. parapsilosis. A marked increase in fluconazole resistance (from 31% to 37.7% and 48.4%, respectively) was also observed. Regarding the total patient population with candidemia (n = 205), fluconazole resistance was independently associated with ICU length of stay (LOS) before candidemia (OR 1.03; CI: 1.01&ndash;1.06, p = 0.003), whereas the presence of shock at candidemia onset was associated with C. albicans (OR 6.89; CI: 2.2&ndash;25, p = 0.001), and with fluconazole-susceptible species (OR 0.23; CI: 0.07&ndash;0.64, p = 0.006). In conclusion, substantial increases in the incidence of candidemia, in non-albicansCandida species, and in fluconazole resistance were found in patients admitted to the ICU due to COVID-19, compared to pre-pandemic periods. At candidemia onset, prolonged ICU LOS was associated with fluconazole-resistant and the presence of shock with fluconazole-susceptible species