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.

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.

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.

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.

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.

Evaluation of miR-506 and miR-4316 expression in early and non-invasive diagnosis of colorectal cancer.

PURPOSE: Examination of the entire colon by colonoscopy remains the golden standard for screening of colorectal cancer (CRC). However, patients are reluctant to perform invasive colonoscopies because of interference with their intimacy. Therefore, the potential use of non-invasive analysis of microRNAs expression in liquid biopsy as a novel biomarker for early CRC has investigated in several studies. In this study, we analyzed the expression of two novel microRNAs: miR-506 and miR-4316, which have never been examined in CRC. METHODS: Plasma samples were collected from 56 patients (median age of 68 years) with operable colorectal cancer and from 70 healthy individuals (median age of 59 years). Expression of plasma microRNAs was evaluated by quantitative reverse transcription polymerase chain reaction using Eco real-time PCR device (Illumina, USA). RESULTS: We found a significant elevated expression of both examined microRNAs in early CRC patients when compared to those in healthy individuals (p = 0.0054 for miR-506 and p = 0.0025 for miR-4316). The expression of miR-506 and miR-4316 did not depend on gender, age, disease stage, and tumor localization of CRC patients. ROC curve analysis showed that both examined microRNAs could differentiate early stage colorectal cancer from healthy individuals with 76.8% specificity and 60.7% sensitivity for miR-506 analysis and 76.8% specificity and 75% specificity for miR-4316 analysis. CONCLUSION: Our study revealed that elevated expression of miR-506 and miR-4316 in peripheral blood were potential molecular markers for early colorectal cancer.

Application of plasma circulating microRNA-448, 506, 4316, and 4478 analysis for non-invasive diagnosis of lung cancer.

Aberrant expression of microRNAs (miRNAs) in cancer patients compared to healthy people as well as possibility of detection of these molecules in blood samples make them potential biomarkers of various cancers. In the present study, we investigated the potential role of four miRNAs as lung cancer (LC) biomarkers: miRNA-448, 506, 4316, and 4478. Using quantitative reverse transcription polymerase chain reaction (qRT-PCR) technique, we assessed expression of studied miRNAs in plasma samples of 90 lung cancer patients and 85 healthy individuals. Receiver operating curves (ROC) with area under the curve (AUC) were used to assess accuracy of studied miRNAs for distinguishing LC patients from healthy individuals. The miRNA-448 and 4478 were significantly overexpressed in lung cancer patients compared to healthy people and these two molecules were qualified for further analysis. Combination ROC analysis of both biomarkers reached 90 % of sensitivity and 76.3 % of specificity (AUC = 0.896) for distinguishing operable (stage IA-IIB) non-small cell lung cancer (NSCLC) patients from healthy subjects. Our results suggest that the examination of miRNAs could be considered as potential lung cancer, non-invasive biomarkers.

Analysis of RTEL1 and PCDHGB6 promoter methylation in circulating-free DNA of lung cancer patients using liquid biopsy: A pilot study.

BACKGROUND: Analysis of epigenetic alterations such as methylation of circulating-free DNA (cf-DNA) expression significantly broadened perspectives of lung cancer (LC) screening. Moreover, methylation of tumor suppressor genes may be analyzed with non-invasive manner in patients' blood samples (liquid biopsy), what underline necessity of detailed investigation of tumor cf-DNA. MATERIAL AND METHODS: The purpose of current study was to assess methylation of RTEL1 and PCDHGB6 promoter regions in cf-DNA of 70 LC patients and 80 healthy individuals using qMSP-PCR technique. Methylation status of both genes has not been investigated in cf-DNA of LC patients before. RESULTS: PCDHGB6 promoter methylation was found in 41.4% of LC patients and in 1.3% of healthy individuals, whereas promoter of RTEL1 was found methylated in 51.4% of LC patients and in 8.8% of healthy individuals. Combined analysis of two markers improved test sensitivity up to 62.9% and specificity up to 90% with area under the curve (AUC) in receiver operating curve (ROC) of 0.755. CONCLUSIONS: The evaluation of RTEL1 and PCDHGB6 promoter methylation may be an useful tool for non-invasive diagnosis of LC in liquid biopsy.

Role of circulating microRNA in hemodialyzed patients.

MicroRNA (miRNA) belongs to the family of non-coding RNAs, which posttranscriptionally regulate gene function. Moreover, accumulating evidence points to an essential role of miRNAs in development and monitoring of kidney disease, though the role of particular miRNAs in patients undergoing hemodialysis is still unclear. This might have consequences. It is possible that measuring a single miRNA in hemodialyzed patients may not provide adequate information about development of many pathological processes. The goal of this review is to highlight the current knowledge in the field of miRNAs, with a special emphasis on their circulation in hemodialyzed patients.

The Relationship between miR-5682 and Nutritional Status of Radiotherapy-Treated Male Laryngeal Cancer Patients.

BACKGROUND: Nutritional deficiencies are frequently observed in patients with head and neck cancer (HNC) undergoing radiation therapy. microRNAs (miRNAs) were found to play an important role in the development of metabolic disorders throughout regulation of genes involved in inflammatory responses. This study aimed to explore the correlation between pre-treatment miR-5682 expression and parameters reflecting nutritional deficits in laryngeal cancer (LC) patients subjected to radiotherapy (RT). METHODS: Expression of miR-5682 was analyzed in plasma samples of 56 male LC individuals. Nutritional status of LC patients was assessed using anthropometric and laboratory parameters, bioelectrical impedance analysis (BIA) and clinical questionnaires. RESULTS: A high expression of miR-5682 was associated with significantly lower values of BMI, fat mass, fat-free mass and plasma albumin at selected periods of RT course. miR-5682 allowed us to distinguish between patients classified with both SGA-C and low albumin level from other LC patients with 100% sensitivity and 69.6% specificity (AUC = 0.820; p < 0.0001). Higher expression of studied miRNA was significantly associated with shorter median overall survival (OS) in LC patients (HR = 2.26; p = 0.008). CONCLUSIONS: analysis of miR-5682 expression demonstrates a potential clinical utility in selection of LC patients suffering from nutritional deficiencies developing as a consequence of RT-based therapy.

Correlation between Neutrophil-to-Lymphocyte Ratio, Platelets-to-Lymphocyte Ratio, C-Reactive Protein-to-Albumin Ratio and Clinical Picture of Elderly Chronic Heart Failure Patients.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR), platelets-to-lymphocyte ratio (PLR) and C-reactive protein-to-albumin ratio (CAR) are believed to be potential inflammatory markers that are closely related to the prognosis and course of cardiovascular diseases. The main goal of this study was the evaluation of NLR, PLR and CAR as factors reflecting the clinical picture and the prognosis of elderly chronic heart failure (CHF) patients. METHODS: In 150 elderly patients with newly diagnosed CHF, the NLR, PLR and CAR were correlated with cardiac, laboratory and nutritional parameters. RESULTS: Systemic inflammatory ratios were correlated with selected patient's parameters. CAR was associated with an unfavorable clinical picture of CHF-a reduced EF (p = 0.007), an elevated PASP (p = 0.014), an increased LVESD in both males and females (p = 0.032 and 0.024, respectively) and a decreased TAPSE (p = 0.023). CAR allowed us to distinguish between NYHA I-III and NYHA IV classes with AUC of 0.830. By analyzing the five-year mortality rate in patients with different CAR values, the greater death rate was recorded for patients with high CAR values-one-year death rate (40.3% vs. 17.2%) and five-year death rate (80% vs. 58.3%) (p = 0.002). Both NLR and PLR correlated only with selected parameters. CONCLUSION: An analysis of inflammatory markers, mainly CAR, allows the management of CHF, because its value can reflect the cardiac and nutritional status of patients with a prognostic value. NLR and PLR can serve as supplementary examinations for CAR evaluation.

The presence of HER2 exon 20 insertion in patients with central nervous system metastases from non-small lung cancer--a potential application in classification for therapy.

INTRODUCTION: HER2 (ErbB2/neu) is a member of the ErbB family of four structurally related receptors of tyrosine kinase activity. Overexpression of ErbB-1 (EGFR) and HER2 is found in many human cancers, but the presence of these genes mutations determines the effectiveness of EGFR and HER2 tyrosine kinase inhibitors in the therapy of non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: To search for insertions of the HER2 gene in exon 20 in 150 brain metastases of non-small cell lung cancer patients, we used a PCR technique based on analysis of amplified DNA fragment lengths. We also compared the HER2 mutational status with clinicopathologic features and the presence of EGFR and BRAF mutations. RESULTS: HER2 mutation was present in one male, non-smoking patient with low differentiated adenocarcinoma (0.67% of all patients and 1.5% of patients with adenocarcinoma). The mutations of EGFR and BRAF genes were not found in HER2-mutated patient. CONCLUSIONS: The literature data suggests that patients with HER2 mutations may be sensitive to tyrosine kinase inhibitors of both EGFR and HER2 receptors (e.g. afatinib). Therefore, the identification of new driver mutations in NSCLC can improve the quality of patient care by enabling the use of correct molecularly targeted therapies.

Depression in Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.

Polycystic ovary syndrome (PCOS) is an endocrine disorder with a broad spectrum of clinical symptoms. Some of the serious complications of PCOS are mental disorders including depression. Therefore, the aim of the meta-analysis was to determine the prevalence, mean level, standardized mean difference and probability of depression based on the research conducted with the Hospital Anxiety and Depression Scale (HADS). A systematic literature search was performed using the following databases: PubMed, EMBASE, Scopus, ClinicalTrials.gov and Google for research published until January 2023. The meta-analysis was conducted on a group of 4002 patients obtained from 19 studies, which met the inclusion criteria (adult pre-menopausal women diagnosed with PCOS, papers on the prevalence of depression or the HADS scoring). According to the research performed, the mean prevalence of depression was 31% (I2 = 93%; p < 0.001), whereas the mean HADS depression score in patients with PCOS was 6.31 (I2 = 93%; p < 0.001). The standardized difference of mean depression scores was SMD = 0.421 (95% confidence interval = 0.17-0.68, I2 = 67%). The overall probability of depression in PCOS patients was more than 2.5-fold higher than in healthy women ((RR: 2.58), confidence interval [1.38-4.85]; I2 = 90%, p < 0.001). The research results imply an increased risk of depressive symptoms in women with PCOS.

Mechanisms of resistance to reversible inhibitors of EGFR tyrosine kinase in non-small cell lung cancer.

Abnormalities of epidermal growth factor receptor (EGFR) in non-small-cell lung cancer (NSCLC) patients consist of EGFR overexpression and EGFR (HER1) gene mutations. Structural dysfunction of the tyrosine kinase domain of EGFR is associated with the clinical response to tyrosine kinase inhibitors (TKI) in patients with NSCLC. The most common EGFR gene mutations occur as either deletions in exon 19 or as substitution L858R in exon 21 and cause a clinically beneficial response to gefinitib or erlotinib treatment. Unfortunately, the majority of patients finally develop resistance to these drugs. Acquired resistance is linked to secondary mutations localised in the EGFR gene, mainly substitution T790M in exon 20. Through intense research a few different mechanisms of resistance to reversible tyrosine kinase inhibitors have been identified: amplification of MET or IGF-1R genes, abnormalities of PTEN and mTOR proteins as well as rare mutations in EGFR and HER2 genes. Extensively investigated new drugs could be of significant efficiency in NSCLC patients with secondary resistance to reversible EGFR TKI.

Blood Circulating Non-Coding RNAs for the Clinical Management of Triple-Negative Breast Cancer.

Triple negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer, and is related to unfavorable prognosis and limited treatment strategies. Currently, there is a lack of reliable biomarkers allowing for the clinical management of TNBC. This is probably caused by a complex molecular background, leading to the development and establishment of a unique tumor phenotype. Recent studies have reported non-coding RNAs (ncRNAs) not only as the most promising class of molecular agents with a high applicability to manage human cancers, including TNBC, but also as robust and non-invasive biomarkers that are able to be monitored in blood circulation, with the application of liquid biopsy. There is a lack of papers discussing the role of blood-circulating ncRNAs as diagnostic, predictive, and prognostic biomarkers for TNBC. In this paper, we summarized the available literature reports on the utility of blood-circulating ncRNAs for TNBC management. Additionally, we supplemented this review by bioinformatics analysis, for better understanding of the role of ncRNAs' machinery in the development of a unique TNBC phenotype.

Impact of depressive disorders on clinical outcomes in patients with chronic heart failure.

Introduction: To date, there are no literature reports of research investigating the relationship between depression and chronic heart failure (CHF) in relation to selected nutritional, cardiac and laboratory parameters. Aim: To compare CHF parameters in relation to nutritional and laboratory parameters between depressed and non-depressed patients. Material and methods: We enrolled 94 CHF individuals from Lubelskie Voivodeship to assess depression prevalence and to compare values of cardiac, laboratory and nutritional parameters between depressed and non-depressed patients. Results: Depression was diagnosed in 66 (70.2%) individuals. We noted significantly lower ejection fraction (EF) (EF%) in the group of depressive patients compared to disease-free individuals (mean EF%: 42 ±12 and 49 ±9; p = 0.030) and worse outcomes in NYHA examination (p < 0.001). Depressed patients had lower body weight (p = 0.023), body mass index (BMI) (p = 0.044), serum albumin concentration (p = 0.015), and hemoglobin concentration (p = 0.042) and an elevated level of C-reactive protein (CRP) (p = 0.025) in comparison to the non-depressed group. The moderate or severely depressed group had a lower level of EF% (p = 0.019) and higher left anterior descending artery (LAD) (p = 0.040) compared with the group suffering from mild depression. We observed greater susceptibility to develop cachexia in patients diagnosed as moderately or severely depressed (p = 0.030). Moreover, in the mentioned group of patients, lower values of body weight (p = 0.037), fat-free mass (FFM) (p = 0.022) and hemoglobin concentration (p = 0.007) were found. Moreover, an inverse correlation between Beck Depression Inventory (BDI) score and EF% (r = -0.371; p = 0.017) was recorded. Conclusions: Depression in CHF patients is associated with worse cardiac, laboratory and nutritional outcomes. Unfavorable clinical characteristics of CHF patients are related to depression severity.

TNFRSF1A Gene Polymorphism (−610 T > G, rs4149570) as a Predictor of Malnutrition and a Prognostic Factor in Patients Subjected to Intensity-Modulated Radiation Therapy Due to Head and Neck Cancer

Background: Malnutrition is a nutritional disorder observed in 52% of patients with head and neck cancer (HNC). Malnutrition is frequently related to the increased level of proinflammatory cytokines. In turn, ongoing inflammation is associated with increased catabolism of skeletal muscle and lipolysis. Tumor necrosis factor α (TNF-α) is a proinflammatory cytokine that plays a pivotal role in the development of malnutrition and cachexia in cancer patients. The aim of the study was to assess the relationship between a functional single-nucleotide polymorphism (SNP) −610 T > G (rs4149570) of the TNFRSF1A gene and the occurrence of nutritional disorders in patients subjected to RT due to HNC. Methods: The study group consisted of 77 patients with HNC treated at the Oncology Department of the Medical University in Lublin. Genotyping of the TNFRSF1A gene was performed using capillary electrophoresis (Genetic Analyzer 3500). Results: Multivariable analysis revealed that the TT genotype of the TNFRSF1A gene (−610 T > G) was an independent predictor of severe malnutrition (odds ratio­OR = 5.05; p = 0.0350). Moreover, the TT genotype of this gene was independently related to a higher risk of critical weight loss (CWL) (OR = 24.85; p = 0.0009). Conclusions: SNP (−610 T > G) of the TNFRSF1A may be a useful marker in the assessment of the risk of nutritional deficiencies in HNC patients treated with intensity-modulated radiotherapy (IMRT).

High miR-511-3p Expression as a Potential Predictor of a Poor Nutritional Status in Head and Neck Cancer Patients Subjected to Intensity-Modulated Radiation Therapy.

Nutritional deficiencies, including malnutrition and its irreversible type cachexia, are often observed in patients with head and neck cancer (HNC). Among the various factors contributing to the occurrence of these disorders, inflammation seems to be crucial. The potential regulatory properties of miR-511-3p, e.g., post-translational alteration of expression of genes with protein products that are involved in inflammation, may be related to nutritional deficiencies observed in HNC patients. Therefore, the aim of our study was to assess the correlation between pretreatment miR-511-3p expression and nutritional status in patients undergoing radiotherapy (RT) due to HNC. In our retrospective study, 60 consecutively admitted patients treated with intensity-modulated radiotherapy (IMRT) due to advanced HNC were enrolled. The analysis of miR-511-3p expression was performed using real-time PCR. Significantly higher expression of miR-511-3p was observed in well-nourished patients compared to patients with moderate or severe malnutrition (p = 0.0001). Pretreatment expression of miR-511-3p may be a useful biomarker of nutritional deficiencies in patients subjected to IMRT due to HNC.