Characterization of Undiscovered miRNA Involved in Tumor Necrosis Factor Alpha-Induced Atrophy in Mouse Skeletal Muscle Cell Line.

Muscular atrophy is a complex catabolic condition that develops due to several inflammatory-related disorders, resulting in muscle loss. Tumor necrosis factor alpha (TNF-α) is believed to be one of the leading factors that drive inflammatory response and its progression. Until now, the link between inflammation and muscle wasting has been thoroughly investigated, and the non-coding RNA machinery is a potential connection between the candidates. This study aimed to identify specific miRNAs for muscular atrophy induced by TNF-α in the C2C12 murine myotube model. The difference in expression of fourteen known miRNAs and two newly identified miRNAs was recorded by next-generation sequencing between normal muscle cells and treated myotubes. After validation, we confirmed the difference in the expression of one novel murine miRNA (nov-mmu-miRNA-1) under different TNF-α-inducing conditions. Functional bioinformatic analyses of nov-mmu-miRNA-1 revealed the potential association with inflammation and muscle atrophy. Our results suggest that nov-mmu-miRNA-1 may trigger inflammation and muscle wasting by the downregulation of LIN28A/B, an anti-inflammatory factor in the let-7 family. Therefore, TNF-α is involved in muscle atrophy through the modulation of the miRNA cellular machinery. Here, we describe for the first time and propose a mechanism for the newly discovered miRNA, nov-mmu-miRNA-1, which may regulate inflammation and promote muscle atrophy.

Effect of the Addition of Dandelion (Taraxacum officinale) on the Protein Profile, Antiradical Activity, and Microbiological Status of Raw-Ripening Pork Sausage.

The study evaluated the effect of adding dandelion extract on the characteristics of raw-ripening pork sausages while reducing the nitrite addition from 150 to 80 mg/kg. The sausages were made primarily from pork ham (80%) and pork jowl (20%). The process involved curing, preparing the meat stuffing, forming the links, and then subjecting the sausages to a 21-day ripening period. Physicochemical parameters such as pH, water activity, and oxidation-reduction potential were compared at the beginning of production and after the ripening process. The study also examined the impact of ripening on protein metabolism in pork sausages and compared the protein profiles of different sausage variants. The obtained research results indicate that dandelion-leaf extract (Taraxacum officinale) were rich in phenolic acids, flavonoids, coumarins, and their derivatives (LC-QTOF-MS method). Antiradical activity test against the ABTS+* and DPPH radical, and the TBARS index, demonstrated that addition of dandelion (0.5-1%) significantly improved the oxidative stability of raw-ripening sausages with nitrite content reduction to 80 mg/kg. A microbiological evaluation of the sausages was also carried out to assess the correctness of the ripening process. The total number of viable bacteria, lactic acid bacteria, and coliforms were evaluated and subsequently identified by mass spectrometry.

Can Dietary Actives Affect miRNAs and Alter the Course or Prevent Colorectal Cancer?

Colorectal cancer is a diet-related cancer. There is much research into the effects of nutrients on the prevention, modulation, and treatment of colorectal cancer. Researchers are trying to find a correlation between epidemiological observations indicating certain dietary components as the originator in the process of developing colorectal cancer, such as a diet rich in saturated animal fats, and dietary components that could eliminate the impact of harmful elements of the daily nutritional routine, i.e., substances such as polyunsaturated fatty acids, curcumin, or resveratrol. Nevertheless, it is very important to understand the mechanisms underlying how food works on cancer cells. In this case, microRNA (miRNA) seems to be a very significant research target. MiRNAs participate in many biological processes connected to carcinogenesis, progression, and metastasis. However, this is a field with development prospects ahead. In this paper, we review the most significant and well-studied food ingredients and their effects on various miRNAs involved in colorectal cancer.

High Level of Irisin as a Marker of Malnutrition in Head and Neck Cancer Patients Subjected to Radiotherapy.

BACKGROUND Head and neck cancers (HNC) are the 7th most prevalent neoplasms in the world. In 50% of these patients, body weight loss and malnutrition are observed before the beginning of therapy. It is known that an important role in the pathomechanism of malnutrition and cachexia is played by the development of inflammation, degradation of muscle fibers, and browning of white adipose tissue (WAT). It was demonstrated that even a slight increase in irisin concentration leads to browning of WAT. MATERIAL AND METHODS The study group consisted of 50 patients with HNC. The nutritional status of the patients was assessed by the Nutritional Risk Score 2002 (NRS 2002) and Subjective Global Assessment (SGA) scales. Using bioelectrical impedance analysis (BIA), the parameters fat mass (FM) and fat-free mass (FFM) were obtained. RESULTS Higher irisin values (1.57 vs 1.18 [ng/ml], P=0.0004) were observed in patients with higher nutritional risk (≥3) evaluated according to the NRS scale. In patients assessed as B or C on the SGA scale, higher values of irisin concentration (1.38 vs 1.07 [ng/ml], P=0.0139) were noted. It was also observed that the level of irisin before treatment was negatively correlated (rho=-0.30, p=0.0350) with FM% and was positively correlated (rho=0.30, p=0.0340) with FFM% in BIA measurements performed after the 7th cycle of RTH. CONCLUSIONS Based on these results, we conclude that patients with malnutrition tend to have higher irisin values compared to normally nourished patients. A high level of irisin may be a useful marker of malnutrition in patients with HNC.

TNF-α Induced Myotube Atrophy in C2C12 Cell Line Uncovers Putative Inflammatory-Related lncRNAs Mediating Muscle Wasting.

BACKGROUND: Muscle atrophy is a complex catabolic condition developing under different inflammatory-related systemic diseases resulting in wasting of muscle tissue. While the knowledge of the molecular background of muscle atrophy has developed in recent years, how the atrophic conditions affect the long non-coding RNA (lncRNAs) machinery and the exact participation of the latter in the mediation of muscle loss are still unknown. The purpose of the study was to assess how inflammatory condition developing under the tumor necrosis factor alpha (TNF-α) treatment affects the lncRNAs' expression in a mouse skeletal muscle cell line. MATERIALS AND METHOD: A C2C12 mouse myoblast cell line was treated with TNF-α to develop atrophy, and inflammatory-related lncRNAs mediating muscle loss were identified. Bioinformatics was used to validate and analyze the discovered lncRNAs. The differences in their expression under different TNF-α concentrations and treatment times were investigated. RESULTS: Five lncRNAs were identified in a discovery set as atrophy related and then validated. Three lncRNAs, Gm4117, Ccdc41os1, and 5830418P13Rik, were selected as being significant for inflammatory-related myotube atrophy. Dynamics changes in the expression of lncRNAs depended on both TNF-α concentration and treatment time. Bioinformatics analysis revealed the mRNA and miRNA target for selected lncRNAs and their putative involvement in the molecular processes related to muscle atrophy. CONCLUSIONS: The inflammatory condition developing in the myotube under the TNF-α treatment affects the alteration of lncRNAs' expression pattern. Experimental and bioinformatics testing suggested the prospective role of lncRNAs in the mediation of muscle loss under an inflammatory state.

Electric Cell-Substrate Impedance Sensing (ECIS) as a Convenient Tool to Assess the Potential of Low Molecular Fraction Derived from Medicinal Fungus Cerrena unicolor in Action on L929 and CT-26 Cell Lines.

The increase in the incidence of cancer has contributed to the search for new therapeutic methods. In recent years, the use of preparations of natural origin from medical fungi has increased. One such active substance is the extracellular, low molecular active fraction obtained from the medicinal fungus Cerrena unicolor. This study aimed to monitor the pharmacokinetics of different concentrations of substances isolated from the medicinal fungus Cerrena unicolor (ex-LMS) using the ECIS technique. In the study, mouse L929 fibroblasts and colon cancer CT26 cell lines were treated with different concentrations of the active fractions obtained from Cerrena unicolor: C1 = 2.285 (µg/mL); C2 = 22.85 (µg/mL); and C3 = 228.5 (µg/mL). This study demonstrated that the tested preparation from Cerrena unicolor had no considerable effect on the resistance, capacitance, and impedance of L929 fibroblast cells, which was an indicator of no significant effect on its physiological processes. At the same time, those parameters exhibited a decrease in colon cancer cell viability. Following our previous and current studies on Cerrena unicolor, ex-LMS extracts can be safely used in anticancer therapy or chemoprevention with no significant harmful effects on normal cells.

Antiproliferative Properties of Triterpenoids by ECIS Method-A New Promising Approach in Anticancer Studies?

Electric cell-substrate impedance sensing is an advanced in vitro impedance measuring system which uses alternating current to determine behavior of cells in physiological conditions. In this study, we used the abovementioned method for checking the anticancer activities of betulin and betulinic acid, which are some of the most commonly found triterpenes in nature. In our experiment, the threshold concentrations of betulin required to elicit antiproliferative effects, verified by MTT and LDH release methods, were 7.8 µM for breast cancer (T47D), 9.5 µM for lung carcinoma (A549), and 21.3 µM for normal epithelial cells (Vero). The ECIS results revealed the great potential of betulin and betulinic acid's antitumor properties and their maintenance of cytotoxic substances to the breast cancer T47D line. Moreover, both substances showed a negligible toxic effect on healthy epithelial cells (Vero). Our investigation showed that the ECIS method is a proper alternative to the currently used assay for testing in vitro anticancer activity of compounds, and that it should thus be introduced in cellular routine research. It is also a valuable tool for live-monitoring changes in the morphology and physiology of cells, which translates into the accurate development of anticancer therapies.

AA genotype of PLIN1 13041A>G as an unfavourable predictive factor of malnutrition associated with fat mass loss in locally advanced head and neck cancer male patients treated with radiotherapy.

INTRODUCTION: Malnutrition is a frequently diagnosed condition in head and neck cancer (HNC) patients after radiation therapy (RTH). Malnutrition causes adipose tissue dysfunction associated with intensified lipolysis and disruption of the activity of mechanisms that protect adipose tissue against this process, which include the protective function of perilipin. MATERIAL AND METHODS: The purpose of this study was the evaluation of the predictive value of 13041A>G PLIN1 polymorphism in the development of malnutrition related to adipose tissue loss in a group of 80 patients with locally advanced HNC treated by means of radical radiation therapy. RESULTS: After the completion of RTH, men with AA genotype had significantly lower fat mass (FM compared to men with G haplotype; FM: 13.84 ± 6.36 kg and 19.06 ± 6.30 kg (p = 0.009). In consequence of RTH, the AA genotype carriers lost an average of 37.01% adipose tissue mass and patients with GA and GG genotypes lost 12.82 and 0.31% (p = 0.035), respectively. AA genotype was also associated with higher chance of ≥ 10%, ≥ 20% and ≥ 30% FM loss in the course of RTH (OR = 13.78; 5.78; 2.28). CONCLUSIONS: The evaluation of such molecular factors as SNP 13041A>G may have higher predictive value in the development of malnutrition associated with severe loss of fat mass than the subjective scales, e.g., SGA and NRS-2002. The presence of AA genotype on men with HNC before RTH may facilitate earlier nutritional intervention and supportive treatment aimed at limiting or preventing body mass and fat mass loss during the applied treatment.

Soluble ST2 proteins in male cachectic patients with chronic heart failure.

BACKGROUND AND AIMS: Until now, there are lack of established clinical factors allowing management of chronic heart failure (CHF) patients being at risk of cardiac cachexia (CC). The changes in soluble protein ST2 (sST2) concentrations suggest a valuable and prognostic usefulness of this biomarker in monitoring patients with CHF, especially those who potentially are prompt to develop CC. The aim of this study was to assess the potential role of sST2 in male patients with CHF under cachexia condition. METHODS AND RESULT: 91 male patients were selected to the study group and underwent meticulous screening according to recent clinical guidelines in order to CHF and CC detection. Additionally all patients underwent assessment of body composition and sST2 testing. Patients were followed-up for 60 months. Plasma sST2 concentration was significantly increased in cachectic compared with non-cachectic patients (median: 27.40 ng/mL and 20.62 ng/mL; p < 0.001), however, in this group the EF% was reduced (mean: 34 ± 13.5% and 41 ± 14.5%; p = 0.029). Correlations between sST2 and CRP (R = 0.524; p < 0.001) and phase angle (PA) (R = -0.513; p < 0.001) were observed. CHF patients in whose the PA value ranged in Q1 (<3.06°) and sST2 concentration ranged in Q3 (>33.15 ng/mL) had higher risk of death (HR = 9.62 and 8.60, respectively). The death rate was the highest in cachectic group with the simultaneous presence of sST2-Q3 and PA-Q1 (87.5% of this group). They had almost 7-fold higher risk of death during follow-up period (HR = 6.89, p < 0.001). CONCLUSIONS: sST2 demonstrates potential utility in male patients with CHF under cachexia condition in prediction death rate.

Serum brain-derived neurotrophic factor (BDNF) concentration predicts polyneuropathy and overall survival in multiple myeloma patients.

Brain-derived neurotrophic factor (BDNF) is a protein with a potent influence on several aspects of neuronal and blood vessel functions. However, its prognostic potential and functional role in multiple myeloma (MM) remain largely unknown. In this study, we investigated the influence of BDNF on the risk of chemotherapy-induced peripheral neuropathy (CIPN) and clinical outcome. Study group consisted of 91 newly-diagnosed MM patients treated with bortezomib and/or thalidomide-based chemotherapy. Detection of BDNF in serum was performed using ELISA. Polyneuropathy was assessed according to the CTCAE Criteria v5. We observed that BDNF concentration correlated with the severity of polyneuropathy (P = 0·0463). Higher BDNF values were noted in patients who responded to treatment (P = 0·0326), and BDNF proved to be a useful marker to predict lack of response after eight cycles of treatment (sensitivity - 100%, specificity - 61·5%, P = 0·0142). Moreover this marker showed significant diagnostic usefulness in diagnosis of CIPN (sensitivity - 76%, specificity - 71·43%; area under the curve (AUC)= 0·77, 95%, confidence interval (CI): 0·64-0·88; P < 0·0001). Low BDNF was an independent, unfavourable prognostic factor associated with reduced overall survival (OS) (hazard ratio (HR) = 2·79, P = 0·0470). In conclusion, BDNF level may play a prognostic role and constitute a useful biomarker in predicting CIPN in MM patients.

Prognostic value of pretreatment neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in multiple myeloma patients treated with thalidomide-based regimen.

Neutrophils to lymphocytes ratio (NLR) and platelets to lymphocytes ratio (PLR) are considered as laboratory markers of inflammation. They can be potentially useful in predicting the course of multiple neoplasms including selected hematological cancers. The aim of the study was to assess the value of NLR and PLR in predicting the effects of therapy and prognosis in multiple myeloma patients treated with thalidomide-based regimen. The study group consisted of 100 patients treated with the first line CTD (cyclophosphamide, thalidomide, and dexamethasone) chemotherapy. The NLR and PLR were calculated before treatment. High NLR was observed in patients with higher stage of the disease, with poor performance status, hypercalcemia, and high CRP. High PLR was associated with low BMI and high CRP. In patients with high NLR, significantly shorter PFS was observed (17 vs. 26 months, p = 0.0405). In addition, high values of NLR and PLR were associated with significantly shorter OS (38 vs. 79 months, p = 0.0010; 40 vs. 78 months, p = 0.0058). Summarizing, NLR and PLR have a significant independent prognostic value for multiple myeloma patients. Furthermore, the NLR can be a predictive marker for the outcome of thalidomide-based chemotherapy.

The relationship between TNF-α gene promoter polymorphism (- 1211 T > C), the plasma concentration of TNF-α, and risk of oral mucositis and shortening of overall survival in patients subjected to intensity-modulated radiation therapy due to head and neck cancer.

PURPOSE: Radiotherapy (RTH) usually combined with chemotherapy (C-RTH) is the main method of treatment in head and neck cancer (HNC). The most common complication of RTH is oral mucositis (OM). At a certain stage of RTH, it occurs in almost all patients, often lead to discontinuation of treatment. Tumour necrosis factor alpha (TNF-α) is a cytokine secreted during inflammatory process accompanying RTH and the development of cancer itself. Single nucleotide polymorphism (SNP) of the TNF-α promoter region can potentially affect the function or expression of this cytokine, and thus modulate the risk of occurrence and intensity of OM and shortening of overall survival (OS). METHODS: The study group consisted of 62 patients with HNC in whom intensity-modulated radiation therapy (IMRT) technique was applied. The plasma TNF-α level was assessed using the ELISA Kit. Genotyping was performed using a real-time PCR method. RESULTS: HNC patients with the CC genotype of TNF-α (- 1211 T > C) have higher TNF-α plasma concentrations than those with T allele (10.70 vs 9.62 ng/ml). Patients with the 3rd degree of OM have significantly higher TNF-α levels after 5th (10.40 vs 9.45 ng/ml) and 7th (10.32 vs 9.60 ng/ml) week of RTH. CC genotype was related to a higher risk of 3rd degree OM development in the last weeks of RTH (5th, OR = 7.33; 7th, OR = 23.15). CONCLUSIONS: High TNF-α plasma concentration and CC genotype of TNF-α are related to the higher risk of more severe OM in patients irradiated due to HNC. High TNF-α plasma concentration and CC genotype of TNF-α are independent prognostic factors for patients subjected to RTH due to HNC.

Anti-cytokine targeted therapies for ANCA-associated vasculitis.

BACKGROUND: Anti-neutrophilic cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) are a group of rare auto-inflammatory diseases that affects mainly small vessels. AAV includes: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). Anti-cytokine targeted therapy uses biological agents capable of specifically targeting and neutralising cytokine mediators of the inflammatory response. OBJECTIVES: To assess the benefits and harms of anti-cytokine targeted therapy for adults with AAV. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (2019, Issue 7), MEDLINE and Embase up to 16 August 2019. We also examined reference lists of articles, clinical trial registries, websites of regulatory agencies and contacted manufacturers. SELECTION CRITERIA: Randomised controlled trials (RCTs) or controlled clinical trials of targeted anti-cytokine therapy in adults (18 years or older) with AAV compared with placebo, standard therapy or another modality and anti-cytokine therapy of different type or dose. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included four RCTs with a total of 440 participants (mean age 48 to 56 years). We analysed the studies in three groups: 1) mepolizumab (300 mg; three separate injections every four weeks for 52 weeks) versus placebo in participants with relapsing or refractory EGPA; 2) belimumab (10 mg/kg on days 0, 14, 28 and every 28 days thereafter until 12 months after the last participant was randomised) or etanercept (25 mg twice a week) with standard therapy (median 25 months) versus placebo with standard therapy (median 19 months) in participants with GPA/MPA; and 3) infliximab (3 mg/kg on days 1 and 14, before the response assessment on day 42) versus rituximab (0.375g/m2 on days 1, 8, 15 and 22) in participants with refractory GPA for up to 12 months. None of the studies were assessed as low risk of bias in all domains: one study did not report randomisation or blinding methods clearly. Three studies were at high risk and one study was at unclear risk of bias for selective outcome reporting. One trial with 136 participants with relapsing or refractory EGPA compared mepolizumab with placebo during 52 weeks of follow-up and observed one death in the mepolizumab group (1/68, 1.5%) and none in the placebo group (0/68, 0%) (Peto odds ratio (OR) 7.39, 95% confidence interval (CI) 0.15 to 372.38; low-certainty evidence). Low-certainty evidence suggests that more participants in the mepolizumab group had ≥ 24 weeks of accrued remission over 52 weeks compared to placebo (27.9% versus 2.9%; risk ratio (RR) 9.5, 95% CI 2.30 to 39.21), and durable remission within the first 24 weeks sustained until week 52 (19.1% mepolizumab versus 1.5% placebo; RR 13.0, 95% CI 1.75 to 96.63; number needed to treat for an additional beneficial outcome (NNTB) 6, 95% Cl 4 to 13). Mepolizumab probably decreases risk of relapse (55.8% versus 82.4%; RR 0.68, 95% CI 0.53 to 0.86; NNTB 4, 95% CI 3 to 9; moderate-certainty evidence). There was low-certainty evidence regarding similar frequency of adverse events (AEs): total AEs (96.9% versus 94.1%; RR 1.03, 95% CI 0.96 to 1.11), serious AEs (17.7% versus 26.5%; RR 0.67, 95% CI 0.35 to 1.28) and withdrawals due to AEs (2.9% versus 1.5%; RR 2.00, 95% CI 0.19 to 21.54). Disease flares were not measured. Based on two trials with different follow-up periods (mean of 27 months for etanercept study; up to four years for belimumab study) including people with GPA (n = 263) and a small group of participants with MPA (n = 22) analysed together, we found low-certainty evidence suggesting that adding an active drug (etanercept or belimumab) to standard therapy does not increase or reduce mortality (3.4% versus 1.4%; Peto OR 2.45, 95% CI 0.55 to 10.97). Etanercept may have little or no effect on remission (92.3% versus 89.5%; RR 0.97, 95% CI 0.89 to 1.07), durable remission (70% versus 75.3%; RR 0.93, 95% CI 0.77 to 1.11; low-certainty evidence) and disease flares (56% versus 57.1%; RR 0.98, 95% CI 0.76 to 1.27; moderate-certainty evidence). Low-certainty evidence suggests that belimumab does not increase or reduce major relapse (1.9% versus 0%; RR 2.94, 95% CI 0.12 to 70.67) or any AE (92.5% versus 82.7%; RR 1.12, 95% CI 0.97 to 1.29). Low-certainty evidence suggests a similar frequency of serious or severe AEs (47.6% versus 47.6%; RR 1.00, 95% CI 0.80 to 1.27), but more frequent withdrawals due to AEs in the active drug group (11.2%) compared to the placebo group (4.2%), RR 2.66, 95% CI 1.07 to 6.59). One trial involving 17 participants with refractory GPA compared infliximab versus rituximab added to steroids and cytotoxic agents for 12 months. One participant died in each group (Peto OR 0.88, 95% CI, 0.05 to 15.51; 11% versus 12.5%). We have very low-certainty evidence for remission (22% versus 50%, RR 0.44, 95% Cl 0.11 to 1.81) and durable remission (11% versus 50%, RR 0.22, 95% CI 0.03 to 1.60), any severe AE (22.3% versus 12.5%; RR 1.78, 95% CI 0.2 to 16.1) and withdrawals due to AEs (0% versus 0%; RR 2.70, 95% CI 0.13 to 58.24). Disease flare/relapse and the frequency of any AE were not reported. AUTHORS' CONCLUSIONS: We found four studies but concerns about risk of bias and small sample sizes preclude firm conclusions. We found moderate-certainty evidence that in patients with relapsing or refractory EGPA, mepolizumab compared to placebo probably decreases disease relapse and low-certainty evidence that mepolizumab may increase the probability of accruing at least 24 weeks of disease remission. There were similar frequencies of total and serious AEs in both groups, but the study was too small to reliably assess these outcomes. Mepolizumab may result in little to no difference in mortality. However, there were very few events. In participants with GPA (and a small subgroup of participants with MPA), etanercept or belimumab may increase the probability of withdrawal due to AEs and may have little to no impact on serious AEs. Etanercept may have little or no impact on durable remission and probably does not reduce disease flare.

Polymorphisms in the promotor region of the CRBN gene as a predictive factor for peripheral neuropathy in the course of thalidomide-based chemotherapy in multiple myeloma patients.

Thalidomide is commonly used in treatment of multiple myeloma (MM). This study aimed to analyse the influence of clinical and molecular factors - single nucleotide polymorphisms (SNPs) of the CRBN gene: rs6768972 and rs1672753, on the risk of adverse effects (AEs) of thalidomide-based chemotherapy in patients with MM. The study group included 82 patients receiving CTD (thalidomide, cyclophosphamide, dexamethasone) as first line treatment. The intensity of haematological and non-haematological AEs was assessed according to the Common Terminology Criteria for Adverse Events v4.03. Multivariate analysis showed that patients with the CRBN CC genotype (rs1672753) had more than a 14-fold higher risk of peripheral polyneuropathy compared to patients with other variants of the investigated SNP [odds ratio (OR) = 14·29]. Carriers of this genotype were burdened with significantly (about 17-fold) higher risk of diarrhoea during treatment (OR = 16·67). The presence of CRBN AA (rs6768972) or TT (rs1672753) genotypes was associated with about 333-fold and 250-fold lower risk of constipation in the course of therapy (OR = 0·003; OR = 0·004, respectively). Selected CRBN SNPs may be useful in assessing the probability of AEs in the form of peripheral polyneuropathy and gastrointestinal motility disorders associated with the use of thalidomide in patients with MM.

Electrical Changes in Polish Patients with Chronic Heart Failure: Preliminary Observations.

Introduction: Direct parameters resistance (R), reactance (Xc), phase angle (PA), capacitance of membrane (Cm), and impedance ratio (Z200/Z5)) determined by bioelectrical impedance analysis (BIA) detect changes in tissue electrical properties and have been found to be a marker of cell membrane function in various diseases. Materials and Method: The cross-sectional study was conducted to investigate whether direct bioimpedance parameters differ in a group of heart failure (HF) patients divided on the basis of the New York Heart Association (NYHA) functional classes I-II and III-IV. BIA was evaluated in 100 patients with HF treated in Clinic of Cardiology and Internal Medicine, Department of Cardiology, Military Hospital, Lublin. Results: In men, lower PA values (p = 0.01), Xc (p < 0.01), Cm (p = 0.02), and higher values of the Z200/Z5 ratio (p < 0.01) were observed in patients classified into NYHA groups III and IV in comparison to those with lower stages of disease. Similar correlations were noted in women (only Cm differences were insignificant). In addition, in men, C-Reactive Protein (CRP) correlated negatively with PA (p < 0.01), Xc (p < 0.01), and Cm (p < 0.01) and positively with the Z200/Z5 index (p < 0.01). There were no similar correlations observed in women. Conclusion: Patients with advanced CHF have altered electrical values. Changes in electrical values may directly reflect tissues as well as the whole-body condition.

Anthropometrical and Bioelectrical Impedance Analysis Parameters in Anorexia Nervosa Patients' Nutritional Status Assessment.

Background and Objectives: Body mass index (BMI) is still the only recommended measurable nutritional status assessment parameter in anorexia nervosa (AN). The aim of this study was to measure other anthropometrical and bioelectrical impedance analysis (BIA) parameters in AN patients and to evaluate their nutritional status assessment value. Materials and Methods: The 46 AN female patients were examined at the beginning of hospitalization and followed-up in three measurements (in 6 ± 2 weeks' intervals). Anthropometrical assessment was based on BMI, circumferences of arm, calf, thigh, hips, waist, their ratio (waist-to-hip ratio (WHR)), and a skinfold test over biceps and triceps muscle, under the scapula, over the hip, and 2 cm from the umbilicus. The BIA parameters included phase angle (PA), membrane capacitance (Cm), and impedance at 200 kHz, and a 5 kHz ratio (Z200/5). Results: In the 1st measurement, BMI correlated with all anthropometric and BIA parameters (p < 0.05). For BIA parameters, the correlation included arm circumference and WHR (p < 0.05). In the follow-up, significant changes were observed in BMI and all BIA parameters. The correlation between BMI and all BIA parameters was present in the 2nd and 3rd measurements (p < 0.05). In the 4th measurement, BMI correlated only with Cm (p = 0.0114). Comparison of BIA parameters according to the state of starvation (BMI < 16.0 kg/m2) revealed that all studied BIA parameters were characterized by statistically significant sensitivity and specificity in the detection of this condition (p < 0.05), except PA in the 4th measurement (p = 0.2099). Conclusions: Selected BIA and anthropometrical parameters could be used for AN patients' assessment. The study confirmed dynamic changes of BIA parameters during the follow-up. They could be useful in the detection of the state of starvation.

[Malnutrition and obesity among patients with rheumatoid arthritis and chronic inflammatory process].

Chronic inflammatory status in patients with rheumatoid arthritis (RA) due to metabolic changes has an effect on body composition. Up to two thirds of patients may be affected by the loss of body cell mass and, thereby, malnutrition including its most severe form - cachexia. Among patients with RA and malnutrition, the total body weight is not reduced and the muscle loss is partially compensated by an increase in body fat. The excess of visceral and trunk adipose tissue is the main factor of increased prevalence of insulin resistance and metabolic syndrome in RA patients. On the other hand, an increased level of abdominal obesity in RA patients is related to the decreased concentration of adiponectin and reduced joint damage, which determines the reduced level of functional impairment. This is the reason why body mass index (BMI) is especially inadequate indicator of body composition in RA patients. In clinical practice, even though BMI is an inadequate body composition indicator, low BMI values in RA patients can be used to detect a particularly fragile sub-set of patients that deserve particular attention. RA patients with BMI intermediate values probably have good control of the disease but they can nonetheless be malnourished. Obese RA patients may or may not have better articular prognosis but should be subjected to the same degree of attention regarding cardiovascular risk factors as obese subjects in the general population. Irrespective of the inflammatory process, body composition is the result of a complex network of interconnected factors, like physical activity, nutritional intake and chronic corticosteroid treatment.

Stimulation of the activity of a novel tannase produced in white-rot fungi Phellinus pini, Fomes fomentarius, and Tyromyces pubescens by medium supplementation.

In recent years, tannase has gained increasing interest mainly because of its potential applications. One of the most important functions of tannic acid (TA) hydrolase is the release of gallic acid (GA) from complex tannins. The aim of the study was to determine the dynamic changes in tannase activity depending on the carbon source in the culture medium. An extracellular and intracellular tannase activity analysis was carried out with the use of spectrophotometric analysis and confirmed by capillary electrophoresis in cultures of white-rot fungi: Phellinus pini, Fomes fomentarius, and Tyromyces pubescens. The inducible potential of TA and rapeseed meal on the activity of tannin acyl hydrolase was confirmed during 14 days of culturing. Different effects of the tested compounds on stimulation of tannase activity in selected fungal strains have been demonstrated. We concluded that rapeseed meal was the best inducer of tannase activity in the case of P. pini. However, the highest concentrations of GA were observed after stimulation by the TA in the cultures of F. fomentarius and T. pubescens.

Bioelectrical impedance phase angle and subjective global assessment in detecting malnutrition among newly diagnosed head and neck cancer patients.

Malnutrition, which can be determined by subjective and objective methods, has a high prevalence in head and neck cancer patients. Subjective Global Assessment is a subjective method of nutritional status evaluation. Phase angle, determined by bioelectrical impedance analysis, is proposed as an objective nutritional marker in various disease conditions. The study was conducted to investigate the association between phase angle and Subjective Global Assessment to validate the determination of the nutrition status in adult patients with head and neck cancer. In a prospective cohort study, patients were classified as either well-nourished or malnourished using the Subjective Global Assessment. Phase angle measured by bioelectrical impedance analysis was planned in 75 naive patients with histologically confirmed head and neck cancer. Receiver operating characteristic curves were estimated using the non-parametric method to determine the optimal cut-off level of phase angle. The study was conducted on a cohort population of 75 patients. Well-nourished patients (n = 45) had a statistically significantly higher (p = 0.005) median phase angle score (5.25º) as compared to those who were malnourished (4.73º) (n = 30). A phase angle cut-off of 4.73 was 80 % sensitive and 56.7 % specific in detecting malnutrition diagnosed by SGA in these populations. Phase angle is considered to be a nutritional indicator in patients with head and neck cancer in detecting malnutrition. Further observations are needed to calculate survival, and validate the prognostic significance of phase angle. For future studies, it is important to indicate the specificity of the PA in comparison to SGA measurement.

Metastatic potential of NET in neoplastic disease.

In response to various stimuli, neutrophils and eosinophils can release neutrophil extracellular traps (NET) consisting of proteolytic enzymes, DNA and other components of the cell nucleus. The NETosis process has been characterized as a mechanism of programmed cell death, which leads to chromatin decondensation and disintegration of organelles, followed by lysis of the cell membrane. In recent years the significant role of neutrophils in the pathogenesis of cancer has been highlighted. The presence of two subpopulations of TAN with different phenotypes and functions - acting antitumor "N1" and the pro-cancerous "N2" - has been discovered. By the release of cytokines and chemokines neutrophils may affect angiogenesis and contribute to escape of tumor cells from immune surveillance. Interactions between cells and the microenvironment are of vital importance both for the preservation of homeostasis in normal tissue and tumor growth. They affect the initiation of disease progression and prognosis. The impact of NETosis on the process of metastasis is evaluated in the context of the functions of the individual components of the NET (MMP-9, CG, NE). Furthermore, presumably the pro- or anti-tumor effect of NETosis depends on many factors including the status of the immune system or tumor microenvironment. Probably the cancer cells can be captured by the NET microenvironment in the same manner as microorganisms. However, the high concentration of proteins released during NETosis can induce their proliferation and inhibit apoptosis, thus promoting tumor growth. A better understanding of NETosis function in tumor progression may lead to the emergence of new prognostic factors and targets for therapy in many types of cancer.