Thirty days of double-strain probiotic supplementation increases monocyte phagocytosis in marathon runners.

Marathon runners, subjected to intense training regimens and prolonged, exhaustive exercises, often experience a compromised immune response. Probiotic supplementation has emerged as a potential remedy to mitigate the impact of prolonged exercise on athletes. Consequently, this study sought to assess the influence of probiotic supplementation on monocyte functionality both before and after the official marathon race. Twenty-seven runners were randomly and double-blindly assigned to two groups: placebo (n 13) and probiotic (PRO) (n 14). Over 30 d, both groups received supplements - placebo sachets containing maltodextrin (5 g/d) and PRO sachets containing 1 × 1010 colony-forming unit Lactobacillus acidophilus and 1 × 1010 colony-forming unit Bifidobacterium bifidum subsp. lactis. Blood samples were collected, and immunological assays, including phagocytosis, hydrogen peroxide production, cytokine levels and monocyte immunophenotyping, were conducted at four different intervals: baseline (start of supplementation/30 d pre-marathon), 24 h-before (1 d pre-marathon), 1 h-after (1 h post-marathon) and 5 d-after (5 d post-marathon). Monocyte populations remained consistent throughout the study. A notable increase in phagocytosis was observed in the PRO group after 30 d of supplementation. Upon lipopolysaccharide stimulation, both PRO and placebo groups exhibited decreased IL-8 production. However, after the marathon race, IL-15 stimulation demonstrated increased levels of 5 d-after, while IL-1-ß, IL-8, IL-10, IL-15 and TNF-α varied across different intervals, specifically within the PRO group. Probiotic supplementation notably enhanced the phagocytic capacity of monocytes. However, these effects were not sustained post-marathon.

Anti-Algics in the Therapeutic Response of Breast and Urological Cancers.

The effect of anti-algics on tumor progression and the overall survival of patients is controversial and remains unclear. Herein, we disclose the in vitro effects of the local anesthetics lidocaine, ropivacaine, and levobupivacaine on breast (MCF7), prostate (PC3, LNCaP), and bladder (TCCSUP, HT1376) cancer cell lines, both as monotherapy and in combination with standard-of-care therapeutics. Assays for cell proliferation, viability, death profile, and migration were performed. Additionally, we explored the clinical outcomes of opioid use through a cross-sectional study involving 200 metastatic prostate cancer patients. The main clinical data collected included the type of opioid therapy administered, dosage, treatment duration, disease progression, and overall survival. Results obtained demonstrate that treatment with local anesthetics has a promising selective anti-tumor effect on these types of cancer, with higher effects when associated with docetaxel. This points out the use of local anesthetics as an added value in the treatment of prostate carcinoma patients. Alternatively, chronic opioid use was correlated with reduced overall survival (p < 0.05) and progression-free survival (p < 0.05) at each treatment line in the observational study. While these results provide valuable insights, larger prospective studies are imperative to comprehensively evaluate the clinical impact of opioid analgesics in prostate cancer patients.

Effect of acute caffeine supplementation before intermittent high-intensity exercise on cytokine levels and psychobiological parameters: A randomized, cross-over, placebo-controlled trial.

The present study aimed to verify the effects of caffeine supplementation on psychobiological parameters and its relationship with inflammatory cytokines in non-athlete subjects. We hypothesized that IL-10 may be responsible for the reduction in fatigue perception in response to caffeine supplementation. It was a randomized, double-blinded, cross-over, placebo-controlled study. Ten non-athlete subjects (26.9 ± 4.01 years old; 73.44 ± 9.57 kg; 15.94 ± 4.32 body fat kg) were evaluated. Sixty-min after caffeine (6 mg-1.kg-1 body mass) or placebo supplementation, high-intensity interval exercise test (1 min at 90% of Wmax and 2 min at 50% of Wmax) was performed to maximum voluntary exhaustion. Cytokine concentrations and psychobiological parameters were evaluated before (BE), immediately after (post-PE) and 1 h after exercise (1 h post-PE). We verify that IL-6 (0.35; 95% CI: 0.13 to 0.56; z = 3.24; p = 0.001; d = 1.14) and IL-10 (9.06; 95% CI 0.41 to 17.70; z = 2.05; p = 0.04; d = 1.12) increases post-PE in CAF group versus PLA group. Still, IL-10 levels were higher in CAF group 1 h post-PE (25.04; 95% CI: 8.95 to 41.31; z = 3.05; p = 0.002; d = 1.9) than PLA group. Moreover, 1 h post-PE vigor level was higher in the CAF group versus PLA group (4.53; 95% CI: 1.27 to 7.80; z = 2.72; p = 0.006; d = 0.46), and fatigue was lower in CAF group than PLA group (-5.08; 95% CI: -9.93 to -0.227; z = -2.05; p = 0.040; d = 0.67). We conclude that 1 h post-PE caffeine was able to decrease fatigue and increase vigor perception. IL-10 levels were higher 1 h post-PE in CAF group, suggesting, according to our hypothesis, that IL-10 may be associated with decrease fatigue perceptions after exercise.

Oxidative stress in bladder cancer: an ally or an enemy?

Bladder cancer (BC) is the most common cancer of the urinary tract and despite all innovations, remains a major challenge due to high morbidity and mortality. Genomic and epigenetic analyses allowed the discovery of new genes and pathways involved in the pathogenesis and regulation of BC. However, the effect on mortality has been modest and the development of new targets for BC treatment are needed. Recent evidence suggests that cancer cells are under increased stress associated with oncogenic transformation, with changes in metabolic activity and increased generation of reactive oxygen species (ROS). The increased amounts of ROS in cancer cells are associated with stimulation of cellular proliferation, promotion of mutations and genetic instability, as well as alterations in cellular sensitivity to anticancer agents. Since these mechanisms occur in cancer cells, there is a close link between oxidative stress (OS) and BC with implications in prevention, carcinogenesis, prognosis, and treatment. We address the role of OS as an enemy towards BC development, as well as an ally to fight against BC. This review promises to expand our treatment options for BC with OS-based therapies and launches this approach as an opportunity to improve our ability to select patients most likely to respond to personalized therapy.

Revisiting colorectal cancer animal model - An improved metastatic model for distal rectosigmoid colon carcinoma.

Colorectal cancer (CRC) is the second most frequent and fatal cancer in Western countries. Understanding its biology with different incidence along the colon and rectum, genetic profile and how these factors contribute to local/distant progression, has been hampered by the lack of a suitable CRC model. We report a reproducible model, using human CRC cell lines (CL) (WiDr, LS1034, C2BBe1) injected (1 × 107 cells/animal) in RNU rats (n = 55) which underwent cecostomy and descending colostomy with mucosal-cutaneous fistula of the sigmoid colon. CL were characterized by immunohistochemistry: CK20, CDX2, P53, vimentin, Ki67, CD44, CD133, E-cadherin, ß-catenin and CEA; cancer stem cells-immune system interaction was studied and tumor progression was assessed with nuclear medicine imaging (99mTc-MIBI). Animals developed locally invasive tumors and with WiDr neural invasion was registered. Cancer stem cells were detected in WiDr (CD44 positive). All the cell lines stimulated the immune system, being WiDr the most aggressive. Imaging studies demonstrated tumor uptake. With this CRC model we can study the microenvironment role and tumor-stroma interactions. All CL developed primary disease, but only the WiDR established neural invasion which may represent a metastatic pathway. This model can help unveiling the underlying metastatic mechanisms, and ultimately test better therapeutic approaches for CRC.

C reactive protein/Albumin ratio as predictor of prognosis in castration resistant metastatic prostate cancer.

OBJECTIVE: To assess the association of C reactive protein/Albumin ratio (CAR) with progression free survival (PFS) and overall survival (OS) in castration resistant metastatic prostate cancer (mCRPC) patients. MATERIALS AND METHODS: A transversal study was conducted, including all patients diagnosed with mCRPC within a Central Hospital Urological Oncology consultation between December 2019 and December 2021 (n = 178) and that were submitted to systemic therapy. CRP and albumin results were collected at the beginning of the systemic treatment for mCRPC in 103 patients and, in 75 patients already under treatment at the start of the study, on that occasion (December 2019). All patients were then followed. CAR was correlated with PFS and OS. OS and PFS were measured from the day the CRP and Alb were collected until the event of interest or the final date of follow-up. The sample was divided in two groups according to an optimal cutoff point found in a ROC curve. RESULTS: The sample showed a median age of 75.76 ± 9.17 years old. Using a cut-off point of 0.22, patients with a CAR ≤ 0.22 (63.2%) showed, compared to CAR > 0.22, longer PFS (15.92 vs. 9.46 months, r = -0.13, p < 0.05) and OS (p = < 0.05, 25,72 vs. 15.79 months, r = -0,24, p < 0.05). Better OS in patients with CAR ≤ 0.22 vs > 0.22 was detected on both the group evaluated at the beginning of systemic treatment (26.96 vs 17.63 months, p < 0.05) and the group of patients already under treatment (23.90 vs 11.54 months, p < 0.05). Dividing the sample according to the first line treatment chosen, we found OS of 26.25 vs 5.9 months (p < 0.05), 27.71 vs 22.57 months (p < 0.05) and 27.36 vs 23.75 months (p = 0.12), for docetaxel, abiraterone and enzalutamide, respectively. CONCLUSIONS: According to this study, higher values of CAR are associated with lower PFS and OS in mCRPC patients. We found a cut-off value of 0.22 providing the best discrimination for prognosis. CAR is a good prognosis biomarker, irrespective of the moment of evaluation and chosen treatment option.

Effect of Multi-Strain Probiotic Supplementation on URTI Symptoms and Cytokine Production by Monocytes after a Marathon Race: A Randomized, Double-Blind, Placebo Study.

(1) Purpose: Performing strenuous exercises negatively impacts the immune and gastrointestinal systems. These alterations cause transient immunodepression, increasing the risk of minor infections, especially in the upper respiratory tract. Recent studies have shown that supplementation of probiotics confers benefits to athletes. Therefore, the objective of the current study was to verify the effects of probiotic supplementation on cytokine production by monocytes and infections in the upper respiratory tract after an acute strenuous exercise. (2) Methods: Fourteen healthy male marathon runners received either 5 billion colony forming units (CFU) of a multi-strain probiotic, consisting of 1 billion CFU of each of Lactobacillus acidophilus LB-G80, Lactobacillus paracasei LPc-G110, Lactococcus subp. lactis LLL-G25, Bifidobacterium animalis subp. lactis BL-G101, and Bifidobacterium bifidum BB-G90, or a placebo for 30 days before a marathon. Plasma cytokines, salivary parameters, glucose, and glutamine were measured at baseline, 24 h before, immediately after, and 1 h after the race. Subjects self-reported upper respiratory tract infection (URTI) using the Wisconsin Upper Respiratory Symptom Survey (WURSS-21). The statistical analyses comprised the general linear model (GLM) test followed by the Tukey post hoc and Student's t-test with p < 0.05. (3) Results: URTI symptoms were significantly lower in the probiotic group compared to placebo. The IL-2 and IL-4 plasma cytokines were lower 24 h before exercise, while the other cytokines showed no significant differences. A lower level of IL-6 produced by monocytes was verified immediately after the race and higher IL-10 at 1 h post. No differences were observed in salivary parameters. Conclusion: Despite the low number of marathoners participating in the study, probiotic supplementation suggests its capability to preserve the functionality of monocytes and mitigate the incidence of URTI.

Early morning kidney transplantation: Perioperative complications.

INTRODUCTION: To reduce cold ischemia time (CIT), many kidney transplants are performed in the early morning. Conducting complex surgeries in the early morning may influence the surgeon's technical capacity and rate of surgical complications (SC). AIM: Evaluate the influence of surgery start hour (SSH) regarding duration of surgery (DS), immediate diuresis (ID), SC and acute rejection (AR); evaluate the influence of CIT regarding SC, ID, and AR. METHODS: 2855 cadaveric transplants performed between June 1980 and March 2018 were retrospectively evaluated. Regarding SSH, two groups were created: Group M (00: 00h-05.59h, n = 253) and Group D (06: 00h - 23: 59h, n = 2602). Analyzing the impact of SSH on DS, ID, SC and AR. Evaluate the relationship between CIT (< 18h, 18-30h and > 30h) on ID, SC and AR utilizing univariate and multivariate statistical analysis with SPSS. RESULTS AND CONCLUSION: Groups M and D were comparable in all evaluated demographic variables (p > 0.05), except cold ischemia time (Group M with higher CIT, p < 0.001). Regarding univariate analysis, Surgery start hour did not influence DS (p = 0.344), and SC (p = 0.264), but related with higher ID (p = 0.028) and AR (p = 0.018). CIT related with immediate diuresis (p = 0.020) and acute rejection (p < 0.001) but did not relate with complications (p = 0.734). Regarding multivariate analysis, SSH only influenced immediate diuresis (p = 0.026) and did not influenced acute rejection (p = 0.055). CIT influenced immediate diuresis (p = 0.019) and acute rejection (p < 0.001). Surgery start hour influences Immediate diuresis. With this study, we conclude that the priority must be a short cold ischemia time.

Effects of carbohydrate and glutamine supplementation on cytokine production by monocytes after exercise in hypoxia: A crossover, randomized, double-blind pilot study.

OBJECTIVES: The aim of this study was to evaluate the combined effects of carbohydrate (CHO) and glutamine (Gln) supplementation on cytokine production by monocytes after exercise until exhaustion performed in hypoxia. METHODS: Fifteen physically active men underwent three exercises until exhaustion with an intensity of 70% maximal oxygen intake at a simulated height of 4500 m under the following supplementation: placebo, CHO (maltodextrin 8%/200 mL for 20 min), and CHO + Gln (Gln 20 g/d for 6 d and maltodextrin 8%/200 mL for 20 min) during exercise and for 2 h of recovery. Analysis of variance for repeated measures followed by the Tukey's post hoc test was realized and P < 0.05 was considered statistically significant. RESULTS: Oxygen saturation of arterial blood (SaO2%) decreased in the three trials compared with baseline. Two hours post-exercise, the SaO2% was high in CHO + Gln condition compared with placebo. Two hours after exercise, interleukin (IL)-1ß decreased compared with post-exercise in placebo and was lower compared with baseline in the CHO + Gln condition. Tumor necrosis factor-α decreased 2 h after exercise compared with baseline and pre-exercise in the CHO + Gln condition. No changes were observed in myeloperoxidase or IL-6 production. Two hours after exercise, Gln decreased compared with baseline and post-exercise in placebo and decreased 2 h after exercise in relation to post-exercise in the CHO condition. Gln increased post-exercise compared with pre-exercise in the CHO + Gln condition. Although erythropoietin did not change in this condition, it was high post-exercise and 2 h after exercise in the placebo condition compared with baseline and 2 h after exercise compared with baseline and pre-exercise in the CHO condition. CONCLUSIONS: Gln supplementation for 6 d before exercise, associated with CHO supplementation during exercise, was able to revert Gln reduction after exercise and after 2 h of recovery and may have contributed to reducing tumor necrosis factor-α production, suggesting a possible anti-inflammatory effect of supplementation.

Probiotic supplementation in marathonists and its impact on lymphocyte population and function after a marathon: a randomized placebo-controlled double-blind study.

Probiotic supplementation arises as playing an immune-stimulatory role. High-intensity and -volume exercise can inhibit immune cell function, which threatens athletic performance and recovery. We hypothesized that 30 days of probiotic supplementation could stabilize the immune system of athletes preventing immune suppression after a marathon race. Twenty-seven male marathonists were double-blinded randomly into probiotic (Bifidobacterium-animalis-subsp.-Lactis (10 × 109) and Lactobacillus-Acidophilus (10 × 109) + 5 g of maltodextrin) and placebo (5 g of maltodextrin) group. They received 30 sachets and supplemented 1 portion/day during 30 days before the race. Blood were collected 30 days before (rest), 1 day before (pre), 1 h after (post) and 5 days after the race (recovery). Both chronic and acute exercise modulated a different T lymphocyte population (CD3+CD4-CD8- T-cells), increasing pre-race, decreasing post and returning to rest values at the recovery. The total number of CD8 T cell and the memory subsets statistically decreased only in the placebo group post-race. Pro-inflammatory cytokine production by stimulated lymphocytes decreased in the probiotic group after the supplementation period. 30 days of probiotic supplementation maintained CD8 T cell and effector memory cell population and played an immunomodulatory role in stimulated lymphocytes. Both, training and marathon modulated a non-classical lymphocyte population regardless of probiotic supplementation.