Iodine enriched kale (Brassica oleracea var. sabellica L.)-The influence of heat treatments on its iodine content, basic composition and antioxidative properties.

Iodine deficiency in the diet globally continues to be a cause of many diseases and disabilities. Kale is a vegetable that has health-promoting potential because of many nutrients and bioactive compounds (ascorbic acid, carotenoids, glucosinolates and phenolic compounds). Brassica vegetables, including kale, have been strongly recommended as dietary adjuvants for improving health. The nutrient and health-promoting compounds in kale are significantly affected by thermal treatments. Changes in phytochemicals upon such activities may result from two contrary phenomena: breakdown of nutrients and bioactive compounds and a matrix softening effect, which increases the extractability of phytochemicals, which may be especially significant in the case of iodine-fortified kale. This study investigated changes of basic composition, iodine, vitamin C, total carotenoids and polyphenols contents as well as antioxidant activity caused by steaming, blanching and boiling processes in the levels of two cultivars of kale (green and red) non-biofortified and biofortified via the application to nutrient solutions in hydroponic of two iodoquinolines [8-hydroxy-7-iodo-5-quinolinesulfonic acid (8-OH-7-I-5QSA) and 5-chloro-7-iodo-8-quinoline (5-Cl-7-I-8-Q)] and KIO3. Thermal processes generally significantly reduced the content of the components in question and the antioxidant activity of kale, regardless of cultivar and enrichment. It was observed that the red cultivar of kale had a greater ability to accumulate and reduce iodine losses during the culinary processes. 8-hydroxy-7-iodo-5-quinolinesulfonic acid showed a protective effect against the treatments used, compared to other enrichments, thus contributing to the preservation of high iodine content.

Exposure of chimaeric embryos to exogenous FGF4 leads to the production of pure ESC-derived mice.

Producing chimaeras constitutes the most reliable method of verifying the pluripotency of newly established cells. Moreover, forming chimaeras by injecting genetically modified embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) into the embryo is part of the procedure for generating transgenic mice, which are used for understanding gene function. Conventional methods for generating transgenic mice, including the breeding of chimaeras and tetraploid complementation, are time-consuming and cost-inefficient, with significant limitations that hinder their effectiveness and widespread applications. In the present study, we modified the traditional method of chimaera generation to significantly speed up this process by generating mice exclusively derived from ESCs. This study aimed to assess whether fully ESC-derived mice could be obtained by modulating fibroblast growth factor 4 (FGF4) levels in the culture medium and changing the direction of cell differentiation in the chimaeric embryo. We found that exogenous FGF4 directs all host blastomeres to the primitive endoderm fate, but does not affect the localisation of ESCs in the epiblast of the chimaeric embryos. Consequently, all FGF4-treated chimaeric embryos contained an epiblast composed exclusively of ESCs, and following transfer into recipient mice, these embryos developed into fully ESC-derived newborns. Collectively, this simple approach could accelerate the generation of ESC-derived animals and thus optimise ESC-mediated transgenesis and the verification of cell pluripotency. Compared to traditional methods, it could speed up functional studies by several weeks and significantly reduce costs related to maintaining and breeding chimaeras. Moreover, since the effect of stimulating the FGF signalling pathway is universal across different animal species, our approach can be applied not only to rodents but also to other animals, offering its utility beyond laboratory settings.

Treatment Costs and Social Burden of Pancreatic Cancer.

(1) Background: Pancreatic cancer is the cancer with the third-highest mortality rate, and forecasts indicate its growing share in morbidity. The basis of treatment is inpatient chemotherapy and there is a strong focus on palliative care. (2) Methods: A literature review was conducted based on the rapid review methodology in PubMed and Cochrane databases. The search was supplemented with publications from the snowball search. Qualitative assessment of included publications was performed using AMSTAR2 modified scheme. (3) Results: The review included 17 publications, of which majority concerned direct costs related to the adopted treatment regimen. Most of the publications focused on comparing the cost-effectiveness of drug therapies and the costs of palliative treatment. Other publications concerned indirect costs generated by pancreatic cancer. They particularly focused on the economic burden of lost productivity due to sickness absence. (4) Conclusion: The increase in the incidence of pancreatic cancer translates into an increase in the costs of the health care system and indirect costs. Due to the significant share of hospitalization in the health care structure, direct costs are increasing. The inpatient treatment regimen and side effects translate into a loss of productivity for patients with pancreatic cancer. Among gastrointestinal cancers, pancreatic cancer generates the second largest indirect costs, although it has a much lower incidence rate than the dominant colorectal cancer. This indicates a significant problem of the economic burden of this cancer.

Quality of Life in Patients with Pancreatic Cancer-A Literature Review.

Pancreatic cancer is the malignant disease with the highest mortality rate, and it ranks third in the world after lung and colon cancer. Identified factors that increase the risk of developing pancreatic cancer include chronic pancreatitis, radiation therapy to the pancreatic area due to another cancer, diabetes mellitus, obesity, smoking, and age. The objective of this study was to present the current state of knowledge on the quality of life of patients diagnosed with pancreatic cancer, factors that determine QoL, and ways of coping with the disease. The low curability and low survival rates of pancreatic cancer significantly affect the quality of life of patients, often in the form of significant deterioration, especially in terms of mental changes, cognitive functions, and coping with the disease. Cognitive decline with comorbid depression is also typical for patients with this type of cancer. Research has shown that the health-related quality of life of patients with pancreatic cancer is low, so further research is needed to improve the situation in this area.

Analysis of the Occurrence of Predicative Factors of Chronic Fatigue in Female Patients with Cancer of the Reproductive Organs with Respect to Stage of Treatment.

The aim of this study was to search for mechanisms contributing to cancer-related fatigue in patients with gynecologic cancer. The study involved 51 women with advanced endometrial cancer and ovarian cancer undergoing chemotherapy. Data were gathered at four points in time. After giving consent, each of the women had their blood drawn several times (before surgery and the first, third, and sixth cycle of chemotherapy) to determine serum levels of pro- and anti-inflammatory cytokines. Empirical data were collected using the MFSI-SF and an original questionnaire. Cancer-related fatigue (CRF) was present at every stage of treatment, but the highest mean scores were noted before cytoreductive surgery (8.745 ± 4.599), and before the sixth cycle of chemotherapy (9.667 ± 4.493). Statistically significant relationships were found between IL-1α, IL-1ß, IL-2, Il-6, and IL-10 and fatigue at different stages of treatment. Older age and an above-normal BMI were the major prerequisite factors for the occurrence of fatigue in female oncological patients. The analysis of changes in cytokine levels and the severity of fatigue may be used to improve our understanding of cancer-related fatigue, and to take action to alleviate the obtrusive symptoms experienced by female patients with cancer of the reproductive organs.

The incidence of eating disorders among upper secondary school female students. / Wystepowanie zaburzen odzywiania wsród uczennic szkól ponadgimnazjalnych.

OBJECTIVES: The aim of the present study is to evaluate the incidence and prevalence of eating disorders in the population of Polish upper secondary school female students, while considering the type of school and living conditions. METHODS: The investigations of eating disorders were conducted between March and June 2017 and covered female students of the upper secondary schools of Szczecin. Selection for the survey was multistep. 1,750 questionnaires were included in the analysis. The study used a tool for screening for the occurrence of eating disorders - the Eating Attitudes Test (EAT-26). RESULTS: Lower scores were observed among higher grade students (EAT-26, EAT dieting) as well as those who did not receive pocket money (EAT dieting, EAT bulimia) (p < 0.05). CONCLUSIONS: (1) Age has proved to be an important prognostic factor for eating disorders. The risk decreased as the age of the examined girls increased. (2) The risk of eating disorders was almost 21 times higher among first and second grade girls.

Primary refractory multiple myeloma: a real-world experience with 85 cases.

This study determined whether 85 patients with multiple myeloma (MM) double-refractory to primary induction therapy with triplet regimens had a homogenous prognosis. The overall response rate (ORR) after the second-line therapy was 51%. Patients who proceeded to immediate autologous stem cell transplantation (ASCT) had better ORR than those who received conventional therapies (62% vs. 31%). The ORR for patients who had ASCT directly after the frontline therapy was higher than for those treated with other regimens as the second line therapy (91% vs. 45%) and offered ASCT as the third-line therapy (91% vs. 55%). The median progression-free survival (PFS) after the second-line therapy and median overall survival were 21.6 months and 35.6 months, respectively. ASCT after the second line treatment (HR = 0.24) was an independent predictor of PFS. Eligible patients with primary refractory MM achieve the most benefit from ASCT, also performed immediately after first line induction therapy.

Mantle Cell Lymphoma of Mucosa-Associated Lymphoid Tissue: A European Mantle Cell Lymphoma Network Study.

While classical nodal mantle cell lymphoma (cMCL) is often associated with involvement of multiple extranodal sites, isolated extranodal disease (ED) at the time of diagnosis is a rare event; data on the outcome of these forms are lacking. On behalf of the European MCL Network, we conducted a retrospective analysis on the clinical characteristics and outcomes of MCL presenting with isolated or predominant ED (MALT MCL). We collected data on 127 patients with MALT MCL diagnosed from 1998 to 2015: 78 patients (61%) were male with a median age of 65 years. The involved sites include: upper airways + Waldeyer ring (40; 32%), gastrointestinal tract (32; 25%), ocular adnexa (17; 13%), oral cavity and salivary glands (17; 13%) and others (13; 1%); 7 patients showed multiple extranodal sites. The median follow-up was 80 months (range: 6-182), 5-year progression-free survival (PFS) was 45% (95% CI: 35-54) and 5-year overall survival (OS) was 71% (95% CI: 62-79). In an explorative setting, we compared MALT MCL with a group of 128 cMCL patients: MALT MCL patients showed a significantly longer PFS and OS compared with nodal cMCL; with a median PFS of 4.5 years vs 2.8 years (p = 0.001) and median OS of 9.8 years vs 6.9 years (p = 0.018), respectively. Patients with MALT MCL at diagnosis showed a more favorable prognosis and indolent course than classical nodal type. This clinical variant of MCL should be acknowledged to avoid possible over-treatment.

Identification of the intermediate filament protein synemin/SYNM as a target of myocardin family coactivators.

Myocardin (MYOCD) is a critical regulator of smooth muscle cell (SMC) differentiation, but its transcriptional targets remain to be exhaustively characterized, especially at the protein level. Here we leveraged human RNA and protein expression data to identify novel potential MYOCD targets. Using correlation analyses we found several targets that we could confirm at the protein level, including SORBS1, SLMAP, SYNM, and MCAM. We focused on SYNM, which encodes the intermediate filament protein synemin. SYNM rivalled smooth muscle myosin (MYH11) for SMC specificity and was controlled at the mRNA and protein levels by all myocardin-related transcription factors (MRTFs: MYOCD, MRTF-A/MKL1, and MRTF-B/MKL2). MRTF activity is regulated by the ratio of filamentous to globular actin, and SYNM was accordingly reduced by interventions that depolymerize actin, such as latrunculin treatment and overexpression of constitutively active cofilin. Many MRTF target genes depend on serum response factor (SRF), but SYNM lacked SRF-binding motifs in its proximal promoter, which was not directly regulated by MYOCD. Furthermore, SYNM resisted SRF silencing, yet the time course of induction closely paralleled that of the SRF-dependent target gene ACTA2. SYNM was repressed by the ternary complex factor (TCF) FLI1 and was increased in mouse embryonic fibroblasts lacking three classical TCFs (ELK1, ELK3, and ELK4). Imaging showed colocalization of SYNM with the intermediate filament proteins desmin and vimentin, and MRTF-A/MKL1 increased SYNM-containing intermediate filaments in SMCs. These studies identify SYNM as a novel SRF-independent target of myocardin that is abundantly expressed in all SMCs.

Expression of Toll-like receptors 2 and 4 on peripheral mononuclear cells (PBMCs) after laparoscopic cholecystectomy.

Increasing evidence suggests that the course and intensity of inflammation, as well as repair processes, developed in response to stress, injury, and trauma, depend on the interaction between immediately released endogenous molecules, called alarmins or danger/damage-associated molecular patterns (DAMPs) and cellular pattern recognition receptors (PRR) including Toll-like receptors (TLRs) and activation of inflammatory/immune cells. Therefore, the aim of this study was to examine the expression of TLRs in peripheral blood mononuclear cells (PBMCs), CD3+, and CD14+ cells in control group and in patients before the laparoscopic cholecystectomy, and three and seven days after surgery. Flow cytometry was used to evaluate expression of TLR2 and TLR4. TLR2 and especially TLR4 expression levels on PBMCs were significantly lower in patients with asymptomatic cholelithiasis than in the control group. Laparoscopic surgery did not induce the significant changes in the expression of TLR2, both on PBMCs and CD3+ and CD14+ cell subpopulations. On the contrary, TLR4 expression level on PBMCs was significantly lower on the third and seventh postoperative day than before surgery. Collectively, the expression levels of cellular TLRs, and especially TLR2 and TLR4, might strongly influence the responsiveness of cells to DAMP activation, and in this way can regulate the intensity of inflammatory response to surgical injury.

Consolidation with 90Y ibritumomab tiuxetan radioimmunotherapy in mantle cell lymphoma patients ineligible for high dose therapy: results of the phase II multicentre Polish Lymphoma Research Group trial, after 8-year long follow-up.

Polish Lymphoma Research Group performed a phase-II trial to test whether 90Y ibritumomab tiuxetan radioimmunotherapy (Y90) may constitute an alternative consolidation for mantle cell lymphoma patients unfit for high-dose therapy. Forty-six patients were consolidated with Y90 following response to the 1st (n = 34) or 2nd line (n = 12) (immuno)chemotherapy. Majority of the patients had advanced disease (stage IV and presence of B-symptoms in 85% and 70%, respectively) and high MIPI (5.8, range 4-7). Consolidation with Y90 increased the complete remission (CR) rate obtained by the 1st line therapy from 41% to 91% and allowed for median PFS of 3.3 and OS of 6.5 years. In the first relapse, CR rate increased from 16% to 75%, while median PFS and OS totaled 2.2 and 6.5 years, respectively. At 8 years, 30% of patients, consolidated in the 1st line CR were alive, without relapse. Toxicity associated with Y90 is manageable, more severe after fludarabine-based regimens.

Primary Cardioprotection Reduces Mortality in Lymphoma Patients with Increased Risk of Anthracycline Cardiotoxicity, Treated by R-CHOP Regimen.

BACKGROUND: Advances in anti-lymphoma therapy prolong overall survival, making late adverse effects, like doxorubicin-related cardiotoxicity, an even more important clinical issue. The effectiveness of cardioprotective strategies with close monitoring, angiotensin-converting enzyme inhibitors and/or ß-blockers as well as liposomal doxorubicin are still unconfirmed in clinical practice. METHODS: This study evaluated the role of a primary cardioprotection strategy in preventing cardiovascular mortality and heart failure occurrence in non-Hodgkin lymphoma (NHL) patients with a high risk of anthracycline cardiotoxicity. Thirty-five NHL patients were subjected prospectively to ramipril and/or bisoprolol at NHL diagnosis, before implementing doxorubicin-containing regimens. Additionally, patients with a diagnosis of asymptomatic/mild heart failure received the liposomal form of doxorubicin. The clinical outcome and frequency of all serious cardiac events were compared with the results in a historical cohort of 62 high-risk cases treated without primary cardioprotection. RESULTS: NHL patients with a primary cardioprotection strategy did not experience cardiovascular deaths in contrast to the retrospective control group where cardiovascular mortality was 14.5% at 3 years (p < 0.05). Primary cardioprotection also decreased the frequency of new cardiotoxicity-related clinical symptoms (2.8 vs. 24.1%; p < 0.05) and prevented the occurrence of cardiac systolic dysfunction (0 vs. 8.5%, respectively; p < 0.05). Although the study was not planned to detect any survival benefit, it demonstrated a trend towards increased response rates (complete response 82 vs. 67%; p not significant) and prolonged survival (projected 5-year overall survival 74 vs. 60%; p < 0.05) for patients treated with primary cardioprotection. CONCLUSIONS: A primary personalized cardioprotection strategy decreases the number of cardiac deaths and may potentially prolong overall survival in NHL patients with increased risk of anthracycline cardiotoxicity.

Expression of endothelin type B receptors (EDNRB) on smooth muscle cells is controlled by MKL2, ternary complex factors, and actin dynamics.

The endothelin type B receptor (ETB or EDNRB) is highly plastic and is upregulated in smooth muscle cells (SMCs) by arterial injury and following organ culture in vitro. We hypothesized that this transcriptional plasticity may arise, in part, because EDNRB is controlled by a balance of transcriptional inputs from myocardin-related transcription factors (MRTFs) and ternary complex factors (TCFs). We found significant positive correlations between the TCFs ELK3 and FLI1 versus EDNRB in human arteries. The MRTF MKL2 also correlated with EDNRB. Overexpression of ELK3, FLI1, and MKL2 in human coronary artery SMCs promoted expression of EDNRB, and the effect of MKL2 was antagonized by myocardin (MYOCD), which also correlated negatively with EDNRB at the tissue level. Silencing of MKL2 reduced basal EDNRB expression, but depolymerization of actin using latrunculin B (LatB) or overexpression of constitutively active cofilin, as well as treatment with the Rho-associated kinase (ROCK) inhibitor Y27632, increased EDNRB in a MEK/ERK-dependent fashion. Transcript-specific primers indicated that the second EDNRB transcript (EDNRB_2) was targeted, but this promoter was largely unresponsive to LatB and was inhibited rather than stimulated by MKL2 and FLI1, suggesting distant control elements or an indirect effect. LatB also reduced expression of endothelin-1, but supplementation experiments argued that this was not the cause of EDNRB induction. EDNRB finally changed in parallel with ELK3 and FLI1 in rat and human carotid artery lesions. These studies implicate the actin cytoskeleton and ELK3, FLI1, and MKL2 in the transcriptional control of EDNRB and increase our understanding of the plasticity of this receptor.

Injury induced expression of caveolar proteins in human kidney tubules - role of megakaryoblastic leukemia 1.

BACKGROUND: Caveolae are membrane invaginations measuring 50-100 nm. These organelles, composed of caveolin and cavin proteins, are important for cellular signaling and survival. Caveolae play incompletely defined roles in human kidneys. Induction of caveolin-1/CAV1 in diseased tubules has been described previously, but the responsible mechanism remains to be defined. METHODS: Healthy and atrophying human kidneys were stained for caveolar proteins, (caveolin 1-3 and cavin 1-4) and examined by electron microscopy. Induction of caveolar proteins was studied in isolated proximal tubules and primary renal epithelial cells. These cells were challenged with hypoxia or H2O2. Primary tubular cells were also subjected to viral overexpression of megakaryoblastic leukemia 1 (MKL1) and MKL1 inhibition by the MKL1 inhibitor CCG-1423. Putative coregulators of MKL1 activity were investigated by Western blotting for suppressor of cancer cell invasion (SCAI) and filamin A (FLNA). Finally, correlative bioinformatic studies of mRNA expression of caveolar proteins and MKL1 were performed. RESULTS: In healthy kidneys, caveolar proteins were expressed by the parietal epithelial cells (PECs) of Bowman's capsule, endothelial cells and vascular smooth muscle. Electron microscopy confirmed caveolae in the PECs. No expression was seen in proximal tubules. In contrast, caveolar proteins were expressed in proximal tubules undergoing atrophy. Caveolar proteins were also induced in cultures of primary epithelial tubular cells. Expression was not enhanced by hypoxia or free radical stress (H2O2), but proved sensitive to inhibition of MKL1. Viral overexpression of MKL1 induced caveolin-1/CAV1, caveolin-2/CAV2 and SDPR/CAVIN2. In kidney tissue, the mRNA level of MKL1 correlated with the mRNA levels for caveolin-1/CAV1, caveolin-2/CAV2 and the archetypal MKL1 target tenascin C (TNC), as did the MKL1 coactivator FLNA. Costaining for TNC as readout for MKL1 activity demonstrated overlap with caveolin-1/CAV1 expression in PECs as well as in atrophic segments of proximal tubules. CONCLUSIONS: Our findings support the view that MKL1 contributes to the expression of caveolar proteins in healthy kidneys and orchestrates the induction of tubular caveolar proteins in renal injury.

Mitochondrial DNA in pediatric leukemia patients.

Numerous studies of mitochondrial DNA (mtDNA) in cancer have shown differences between mtDNA sequences in tumor and normal tissue and at various stages of cancer treatment in the same patient. However, there is little data on acute lymphoblastic leukemia (ALL), the most common type of leukemia in children. In this study we compared mitochondrial sequence variation in the D-loop region and in 5 genes of mtDNA in bone marrow samples of 6 pediatric patients with ALL at various stages of therapy. We found several common polymorphisms and one variant at position 3688 whose level varied during leukemia treatment. Our results suggest that mitochondrial DNA mutations, whose levels change during patient treatment, could be potential biomarkers for monitoring treatment efficacy and disease progression.

Synthesis and Biological Evaluation of Fluorinated 3-Phenylcoumarin-7-O-Sulfamate Derivatives as Steroid Sulfatase Inhibitors.

In the present work, we report the initial results of our study on a series of 3-phenylcoumarin sulfamate-based compounds containing C-F bonds as novel inhibitors of steroid sulfatase. The new compounds are potent steroid sulfatase inhibitors, possessing more than 10 times higher inhibitory potency than coumarin-7-O-sulfamate. In the course of our investigation, compounds 2b and 2c demonstrated the highest inhibitory effect on the enzymatic steroid sulfatase assay; both had IC50 values of 0.27 µm (the IC50 value of coumarin-7-O-sulfamate is 3.5 µm, used as a reference).

Lenalidomide in heavily pretreated refractory diffuse large B-cell lymphoma: a case report.

INTRODUCTION: In diffuse large B-cell lymphoma, first-line treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone; salvage with cisplatin-based regimens for relapsing patients; and autologous stem cell therapy are standards of care. Treatment approaches are less clear for patients who are refractory or who are not candidates for autologous stem cell therapy. Options may include palliative regimens or clinical trial enrollment. One therapy under investigation in diffuse large B-cell lymphoma is lenalidomide, an immunomodulatory agent with antiangiogenic activity. CASE PRESENTATION: We present the case of a 55-year-old Caucasian male patient diagnosed with diffuse large B-cell lymphoma who had an early relapse after treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. He then had a subsequent early relapse after cisplatin-based salvage consolidated with autologous stem cell therapy. The efficacy of gemcitabine-cisplatin-rituximab was limited to five months, followed by systemic and central nervous system progression. Fourth-line treatment with lenalidomide plus rituximab and involved-field radiotherapy followed by lenalidomide monotherapy greatly improved this patient's quality of life and performance status, allowing over two years of progression-free survival to date (excluding a brief relapse due to treatment interruption). CONCLUSION: A lenalidomide-based regimen was highly effective in this patient with diffuse large B-cell lymphoma.

Central nervous system prophylaxis with intrathecal liposomal cytarabine in diffuse large B-cell lymphomas.

INTRODUCTION:  Central nervous system (CNS) involvement is a serious and potentially fatal complication in patients with lymphoma because it is associated with a particularly poor prognosis (median progression­free survival [PFS] of 4-6 months). Although CNS prophylaxis is considered necessary, there are no clear guidelines on identifying high­risk patients or selecting treatment regimen.  OBJECTIVES:  The aim of the study was to assess the safety and efficacy of CNS prophylaxis with intrathecal liposomal cytarabine. PATIENTS AND METHODS:  We analyzed the data of 79 patients (46 men and 33 women; median age, 48.5 years [20-79]) with diffuse large B­cell lymphoma (83.5% of the patients) and primary mediastinal large B­cell lymphoma (16.5%). Patients were treated in the departments of hematology in Kraków and Wroclaw, Poland, between the years 2009-2012. They were considered to be at a high risk of developing CNS involvement associated with a lymphoma. RESULTS:  Adverse reactions after intrathecal liposomal cytarabine were reported in 59 patients (74.7%); in 7 cases, the reactions were severe. The most common side effect was headache (67.1%). During antilymphoma therapy and prophylaxis, the functional status assessed by the Karnofsky score improved in 56 patients (70.9%) and remained unchanged in the remaining cases. A median follow­up time did not exceed 28 months (range, 1.4-52.1); during follow­up, neither median overall survival (OS) nor PFS were reached (projected OS and PFS at 48 months are 86.1% and 90.1%, respectively).  CONCLUSIONS:  Our results encourage the use of intrathecal liposomal cytarabine in CNS prophylaxis in patients with lymphoma.