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PB2162: Increased oxidative stress in diffuse large B-cell lymphoma
Get PDFBackground: Oxidative stress is caused by imbalance between excessive production of reactive oxygen species and decreased capabilities of antioxidant system, and it is recognized as a feature in cancerogenesis, as well in hematologic malignancies. Previous studies have shown increasing expression of oxidative stress markers and antioxidant enzymes in lymph nodes progressing to aggressive lymphomas.
Aims: The aim of our study was to assess the clinical and prognostic significance of oxidative stress markers in patients with untreated diffuse large B-cell lymphoma (DLBCL).
Methods: We analysed 64 patients diagnosed with DLBLC during 2018 and 2019, while 27 healthy volunteers (51.9% males) served as a control group. The plasma sample and laboratory analyses were obtained prior to initiation of specific hematologic treatment. After completion of the therapy, the patients were followed up for up to 4 years and for each of them progression free survival (PFS) and overall survival (OS) were calculated. Malondialdehyde (MDA) and protein carbonyl (PC) were used as markers of oxidative stress in plasma of patients and volunteers, while catalase is used as an antioxidant marker.
Results: The mean patients’ age was 56.2 years (range, 20–87); 51.6% were males. Majority of patients were analysed before 1L therapy (n=61; 95,3%), and had following clinical stages: Ann Arbor stage I 23.4%, stage II 37.5%, stage III 15.6% and stage IV 23.4%. Majority of the patients had satisfactory performance status (73.5% had ECOG PS ≥1), bulky tumorous mass was present in 34.4% of patients, whereas 70.3% had extranodal localisation of lymphoma. MDA (6.66±2.7 nmol/ml) was significantly increased (p<0.001, 2.6-fold), while PC (4.29±2.7 nmol/mg) was also significantly increased (p=0.0027, 5-fold) in patients with DLBCL compared to healthy volunteers. In opposite, antioxidant catalase (0.194±0.06 IU/ml) was significantly reduced (p=0.0034, 1.9-fold) in patients with DLBCL. MDA was in significant (p<0.05) negative correlation with hemoglobin (r2=0.586) and LDH (r2=0.59) levels before chemotherapy. MDA was in significant (p<0.01) positive correlation with the age (r2=0.769) of patients with DLBCL at diagnosis. Moreover, MDA was in significant positive correlation with overall survival (p<0.01, r2=0.736) and progression-free survival (p<0.01, r2=0.736) of patients with DLBCL. PC was in negative correlation with the clinical stage (r2=0.103, p=0.146) and therapy response (r2=0.136, p=0.091) of DLBCL but did not reach significance.
Summary/Conclusion: The elevated oxidative markers and reduced antioxidant support oxidative stress in patients with DLBCL, while MDA can be a prognostic marker of overall survival
Application of Perinatal Derivatives on Oncological Preclinical Models: A Review of Animal Studies
Get PDFThe increasing cancer incidence has certified oncological management as one of the most critical challenges for the coming decades. New anticancer strategies are still needed, despite the significant advances brought to the forefront in the last decades. The most recent, promising therapeutic approaches have benefitted from the application of human perinatal derivatives (PnD), biological mediators with proven benefits in several fields beyond oncology. To elucidate preclinical results and clinic outcomes achieved in the oncological field, we present a narrative review of the studies resorting to animal models to assess specific outcomes of PnD products. Recent preclinical evidence points to promising anticancer effects offered by PnD mediators isolated from the placenta, amniotic membrane, amniotic fluid, and umbilical cord. Described effects include tumorigenesis prevention, uncontrolled growth or regrowth inhibition, tumor homing ability, and adequate cell-based delivery capacity. Furthermore, PnD treatments have been described as supportive of chemotherapy and radiological therapies, particularly when resistance has been reported. However, opposite effects of PnD products have also been observed, offering support and trophic effect to malignant cells. Such paradoxical and dichotomous roles need to be intensively investigated. Current hypotheses identify as explanatory some critical factors, such as the type of the PnD biological products used or the manufacturing procedure to prepare the tissue/cellular treatment, the experimental design (including human-relevant animal models), and intrinsic pathophysiological characteristics. The effective and safe translation of PnD treatments to clinical practice relies on the collaborative efforts of all researchers working with human-relevant oncological preclinical models. However, it requires proper guidelines and consensus compiled by experts and health workers who accurately describe the methodology of tissue collection, PnD isolation, manufacturing, preservation, and delivery to the final user
Evaluation of Dietary Intake and Anthropometric Status in 1–9-Year-Old Children Living in Serbia: National Food Consumption Survey according to the EU Menu Methodology
Get PDFThe Serbian Food Consumption Survey among 1–9-year-old-children was conceptualized and conducted in compliance with the principles, established protocols, and guidelines of the EU Menu project between 2017 and 2021. Valid data were collected for 576 individuals (290 1–3-year-old toddlers and 276 3–9-year-old children). Regardless of age and gender category, the majority (68.80%) of children had normal weights according to the Body Mass Index-for-age classification system. The median daily energy intake was 1406.71 kcal with no differences between the settlement types. The overall median contributions of carbohydrates, protein, and fat to the total energy intake were 47.54%, 14.06%, and 37.88%, respectively. The proportions of the macronutrient intake deviated from the dietary reference values with compliance to the recommendations being particularly poor for fat and fiber. The consumption of energy-dense food groups such as meat and meat products, fat and oil, sugar, and confections was more pronounced among older children. The survey results provide a valuable insight into the nutritional status and dietary habits of toddlers and children 1–9 years old living in Serbia. They may serve as an evidence platform for public health programs, a valuable asset for decision-makers, and a reliable reference to guide nutritional policies, diet monitoring, and interventions targeting this population group in the future
Effects of online parietal transcranial electric stimulation on associative memory: a direct comparison between tDCS, theta tACS, and theta-oscillatory tDCS
Get PDFAssociative memory (AM) is the ability to remember and retrieve multiple items bound together. Previous studies aiming to modulate AM by various transcranial electric stimulation (tES) techniques were inconclusive, although overall suggestive that tES could be a tool for AM enhancement. However, evidence from a direct comparison between different tES techniques is lacking. Here, in a sham-controlled cross-over experiment, we comparatively assessed the effects of three types of tES—anodal tDCS, theta-band transcranial alternating current stimulation (tACS), and theta-oscillatory tDCS (otDCS), delivered over the left posterior parietal cortex, during a short-term digit-color AM task with cued-recall. The effects were tested in 40 healthy young participants while both oscillatory tES were delivered at a previously determined individual theta frequency (4–8 Hz). All three active stimulations facilitated the overall AM performance, and no differences could be detected between them on direct comparison. However, unlike tDCS, the effects of which appeared to stem mainly from the facilitation of low-memory demand trials, both theta-modulated tACS and otDCS primarily promoted AM in high memory demand trials. Comparable yet differential effects of tDCS, theta tACS, and otDCS could be attributed to differences in their presumed modes of action
The effects of fish oil supplementation during pre- and perinatal period on fatty acid profile of brain phospholipids in 5xFAD transgenic mice model of Alzheimer's disease
No full textMulti-targeted anticancer activity of human amniotic membrane homogenate on various cancer cells
No full textINTRODUCTION:
Based on the 2020 GLOBOCAN data, bladder cancer ranks as one of the ten most common cancer types throughout the
world. Despite its increasing incidence and high recurrence rates, there have been no significant improvements in the standard
treatment options of bladder cancer. Human amniotic membrane (hAM) is an innermost fetal membrane, which is associated
with a wide range of biological properties such as anti-inflammatory, anti-fibrotic and anti-microbial activity. Furthermore,
recent studies have underlined the possibility that human amniotic membrane (hAM) might also act as a promising anti-cancer agent.
OBJECTIVES:
The aim of this study was to evaluate the anticancer effect of hAM homogenate on 2D and 3D cancer in vitro models.
METHOD / DESIGN:
Human muscle-invasive bladder cancer urothelial (T24) cells, papillary cancer urothelial (RT4) cells, normal porcine urothelial
(NPU) cells, human mammary gland nontumorigenic (MCF10a) cells and low-metastatic breast cancer (MCF7) cells were
treated with different hAM homogenate preparations at different time points. The effect of hAM homogenate on the desquamation
of cancer cells, their attachment capacity, proliferation rate and spheroid architecture was evaluated.
RESULTS:
After 24-hour treatment with hAM homogenate, we observed gradual desquamation of cancerous cells, while normal cells
remained firmly attached to the culture surface. We observed that hAM homogenate caused the highest desquamation of
bladder cancer cells in a time-dependent manner. Additionally, we demonstrated that hAM homogenate not only caused
desquamation but also significantly decreased the adhesion, growth and proliferation rate of human bladder invasive and
papillary cancer cells, whereas it did not affect the normal urothelial cells. In addition, with the help of light and electron
microscopy, we showed that hAM homogenate disrupted the 3D structure of bladder cancer spheroids.
CONCLUSIONS:
The obtained results further strengthen the idea for the potential clinical application of hAM in bladder cancer treatment.
Nevertheless, additional in vitro and in vivo studies are needed to identify the main molecules inside the hAM that exert the
anti-cancer effect and to elucidate their cell biological mechanism of action
Extracellular Vesicles in Musculoskeletal Pathologies and Regeneration
Get PDFThe incidence of musculoskeletal diseases is steadily increasing with aging of the population. In the past years, extracellular vesicles (EVs) have gained attention in musculoskeletal research. EVs have been associated with various musculoskeletal pathologies as well as suggested as treatment option. EVs play a pivotal role in communication between cells and their environment. Thereby, the EV cargo is highly dependent on their cellular origin. In this review, we summarize putative mechanisms by which EVs can contribute to musculoskeletal tissue homeostasis, regeneration and disease, in particular matrix remodeling and mineralization, pro-angiogenic effects and immunomodulatory activities. Mesenchymal stromal cells (MSCs) present the most frequently used cell source for EV generation for musculoskeletal applications, and herein we discuss how the MSC phenotype can influence the cargo and thus the regenerative potential of EVs. Induced pluripotent stem cell-derived mesenchymal progenitor cells (iMPs) may overcome current limitations of MSCs, and iMP-derived EVs are discussed as an alternative strategy. In the last part of the article, we focus on therapeutic applications of EVs and discuss both practical considerations for EV production and the current state of EV-based therapies
Research and innovation as a catalyst for food system transformation
Get PDFBackground: Food systems are associated with severe and persistent problems worldwide. Governance approaches aiming to foster sustainable transformation of food systems face several challenges due to the complex nature of food systems. Scope and approach: In this commentary we argue that addressing these governance challenges requires the development and adoption of novel research and innovation (R&I) approaches that will provide evidence to inform food system transformation and will serve as catalysts for change. We first elaborate on the complexity of food systems (transformation) and stress the need to move beyond traditional linear R&I approaches to be able to respond to persistent problems that affect food systems. Though integrated transdisciplinary approaches are promising, current R&I systems do not sufficiently support such endeavors. As such, we argue, we need strategies that trigger a double transformation - of food systems and of their R&I systems. Key Findings and Conclusions: Seizing the opportunities to transform R&I systems has implications for how research is done - pointing to the need for competence development among researchers, policy makers and society in general - and requires specific governance interventions that stimulate a systemic approach. Such interventions should foster transdisciplinary and transformative research agendas that stimulate portfolios of projects that will reinforce one another, and stimulate innovative experiments to shape conditions for systemic change. In short, a thorough rethinking of the role of R&I as well as how it is funded is a crucial step towards the development of the integrative policies that are necessary to engender systemic change - in the food system and beyond
Polyphenol-Rich Aronia melanocarpa Juice Consumption Affects LINE-1 DNA Methylation in Peripheral Blood Leukocytes in Dyslipidemic Women
Get PDFCardiovascular disease (CVD) is associated with alterations in DNA methylation and polyunsaturated fatty acid (PUFA) profile, both modulated by dietary polyphenols. The present parallel, placebo-controlled study (part of the original clinical study registered as NCT02800967 at www.clinicaltrials.gov) aimed to determine the impact of 4-week daily consumption of polyphenol-rich Aronia melanocarpa juice (AMJ) treatment on Long Interspersed Nucleotide Element-1 (LINE-1) methylation in peripheral blood leukocytes and on plasma PUFAs, in subjects (n = 54, age range of 40.2 ± 6.7 years) at moderate CVD risk, including an increased body mass index, central obesity, high normal blood pressure, and/or dyslipidemia. The goal was also to examine whether factors known to affect DNA methylation (folate intake levels, MTHFR C677T gene variant, anthropometric and metabolic parameters) modulated the LINE-1 methylation levels upon the consumption of polyphenol-rich aronia juice. Experimental analysis of LINE-1 methylation was done by MethyLight method. MTHFR C677T genotypes were determined by the polymerase chain reaction–restriction fragment length polymorphism method, and folate intake was assessed by processing the data from the food frequency questionnaire. PUFAs were measured by gas–liquid chromatography, and serum lipid profile was determined by using Roche Diagnostics kits. The statistical analyses were performed using Statistica software package. In the comparison after vs. before the treatment period, in dyslipidemic women (n = 22), we observed significant decreases in LINE-1 methylation levels (97.54 ± 1.50 vs. 98.39 ± 0.86%, respectively; P = 0.01) and arachidonic acid/eicosapentaenoic acid ratio [29.17 ± 15.21 vs. 38.42 (25.96–89.58), respectively; P = 0.02]. The change (after vs. before treatment) in LINE-1 methylation directly correlated with the presence of MTHFR 677T allele, average daily folate intake, and the change in serum low-density lipoprotein cholesterol but inversely correlated with the change in serum triacylglycerols (R = 0.72, R2 = 0.52, adjusted R2 = 0.36, P = 0.03). The current results imply potential cardioprotective effects of habitual polyphenol-rich aronia juice consumption achieved through the modifications of DNA methylation pattern and PUFAs in subjects at CVD risk, which should be further confirmed. Hence, the precision nutrition-driven modulations of both DNA methylation and PUFA profile may become targets for new approaches in the prevention of CVD
Raman spectral analysis of the brainstem and responses of neuroglia and cytokines in whole-body gamma-irradiated rats after administration of aminothiol-based radioprotector GL2011
Get PDFThe search for an effective and non-toxic radioprotector is ongoing. We tested a novel, natural aminothiol-based radioprotector, GL2011, that was applied 30 min, 3 h or 6 h after the exposure of male albino Wistar rats to a 6.7 Gy mild dose of gamma radiation. The molecular signatures of radioprotection were investigated with Raman microspectroscopy of brainstem tissue samples. Morphological changes and activation of astrocytes and microglia were assessed by immunohistochemistry. Global markers of neuroinflammation were followed by ELISA to monitor blood plasma levels of proinflammatory (IL-6 and TNF-α) and anti-inflammatory (IL-10) cytokines. A thirty-day follow-up determined survival of unprotected animals 37.5%. A survival increase was observed after radioprotection (75%, irrespective of the time of application). Raman spectra revealed a slightly deleterious effect of radiation on nucleic acids in surviving animals that was mitigated with the radioprotector, as GL2011 preserved the morphology of both astrocytes and microglia, with reduced microglial infiltration. Cytokine assessment revealed an immunomodulatory effect of the novel radioprotector. The overall results point out the positive effects of a single dose of GL2011 applied at different times. The molecular and cellular changes in the brainstem indicate that the radioprotector applied after radiation conferred better protection, which underlines its translation to cure radiation accidents