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Background: Berberine is the main active compound of different herbs and is defined as an isoquinoline quaternary botanical alkaloid found in barks and roots of numerous plants. It exhibits a wide range of pharmacological effects, such as anti-obesity and antidiabetic effects. Berberine has antibacterial activity against a variety of microbiota, including many bacterial species, protozoa, plasmodia, fungi, and trypanosomes., Objective: This review describes the role of berberine and its metabolic effects. It also discusses how it plays a role in glucose metabolism, fat metabolism, weight loss, how it modulates the gut microbiota, and what are its antimicrobial properties along with its potential side effects with maximal tolerable dosage., Methods: Representative studies were considered and analyzed from different scientific databases, including PubMed and Web of Science, for the years 1982-2022., Results: Literature analysis shows that berberine affects many biochemical and pharmacological pathways that theoretically yield a positive effect on health and disease. Berberine exhibits neuroprotective properties in various neurodegenerative and neuropsychological ailments. Despite its low bioavailability after oral administration, berberine is a promising tool for several disorders. A possible hypothesis would be the modulation of the gut microbiome. While the evidence concerning the aging process in humans is more limited, preliminary studies have shown positive effects in several models., Conclusion: Berberine could serve as a potential candidate for the treatment of several diseases. Previous literature has provided a basis for scientists to establish clinical trials in humans. However, for obesity, the evidence appears to be sufficient for hands-on use., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Iron (Fe) is a necessary trace element in numerous pathways of human metabolism. Therefore, Fe deficiency is capable of causing multiple health problems. Apart from the well-known microcytic anemia, lack of Fe can cause severe psychomotor disorders in children, pregnant women, and adults in general. Iron deficiency is a global health issue, mainly caused by dietary deficiency but aggravated by inflammatory conditions. The challenges related to this deficiency need to be addressed on national and international levels. This review aims to summarize briefly the disease burden caused by Fe deficiency in the context of global public health and aspires to offer some hands-on guidelines., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose of This Review: This review will focus on the neglected side of metabolic support in ICU survivors: nutritional therapy after critical illness. Knowledge of the evolution of the metabolism of patients that survived critical illness will be bundled, and current practices will be investigated. We will discuss some studies conducted to determine resting energy expenditure in ICU survivors and which identified barriers that cause interruptions in the feeding process based on published data between January 2022 and April 2023., Recent Findings: Resting energy expenditure can be measured using indirect calorimetry, as predictive equations have proven to fail in their attempt to have good correlations with measured values. No guidelines or recommendations are available on post-ICU follow-up, including screening, assessment, dosing, timing, and monitoring of (artificial) nutrition. A limited number of publications shared treatment adequacy between 64-82% for energy (calories) and 72-83% for protein intake in a post-ICU setting. Loss of appetite, depression, and oropharyngeal dysphagia are the most prominent physiological barriers responsible for decreased feeding adequacy., Summary: Patients may be in a catabolic state during and after ICU discharge, with several factors impacting metabolism. Therefore, large prospective trials are needed to determine the physiological state of ICU survivors, determine nutritional requirements, and develop nutritional care protocols. Many barriers causing decreased feeding adequacy have already been identified, but solutions are scarce. This review depicts a variable metabolic rate among ICU survivors and a significant variation in feeding adequacy in-between world regions, institutions, and patient sub-phenotypes., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Gut microbes share a symbiotic relationship with humans and perform several metabolic and physiological functions essential for human survival. It has been established in several scientific studies that obesity and other metabolic complications are always associated with disturbed gut microbiota profile, also called gut dysbiosis. In recent years, bariatric surgery has become a treatment of choice for weight loss, and it forms an important part of obesity management strategies across the globe. Interestingly, bariatric surgery has been shown to alter gut microbiota profile and synthesize short-chain fatty acids by gut microbes. In other words, gut microbes play a crucial role in better clinical outcomes associated with bariatric surgery. In addition, gut microbes are important in reducing weight and lowering the adverse events post-bariatric surgery. Therefore, several prebiotics, probiotics and postbiotics are recommended for patients who underwent bariatric surgery procedures for better clinical outcomes. The present review aims to understand the possible association between gut microbes and bariatric surgery and present scientific evidence showing the beneficial role of gut microbes in improving therapeutic outcomes of bariatric surgery.

Bariatric surgery or weight loss surgery has been in practice for achieving significant weight loss in patients who have failed to achieve weight loss after pharmacological interventions. The rising cases of obesity are a triggering factor for more bariatric surgeries worldwide. Interestingly, sustained weight loss achieved post-bariatric surgery offers metabolic advantages, and patients show improved glucose and lipid metabolisms. Bariatric surgery is directly linked to higher incidences of vitamin, mineral, and trace element deficiencies, thus making patients susceptible to anemia, osteoporosis, and cardiomyopathy. Reduced nutrient absorption capacity, dietary changes, dietary restriction, and altered gastrointestinal tract morphology are some reasons for nutritional deficiency observed in post-bariatric surgery procedures. Micro-and-macronutrient deficiency observed in patients during the postoperative phase requires continuous monitoring of nutritional parameters. Therefore, adequate multivitamin and mineral supplements become essential to prevent/overcome micronutrient deficiencies. Bariatric surgery also raises the risk of small for gestational age (SGA) babies. Hence, a 12 - 24 months gap is recommended between bariatric surgery and pregnancy to achieve desired weight loss targets. The topic of this review is the impact of bariatric surgery procedures on vitamin and mineral absorption and the role of dietary supplements in maintaining a healthy nutritional balance during the postoperative phase.

Prostate disorders are commonplace in medicine, especially in older men, with prostatitis, benign prostatic hyperplasia, and prostate cancer being the most abundant pathologies. The complexity of this organ, however, turns treatment into a challenge. In this review, we aim to provide insight into the efficacy of alternative treatments, which are not normally used in conventional medicine, with a particular focus on nutrients. In order to understand why and how nutrition can be beneficial in diseases of the prostate, we give an overview of the known characteristics and features of this organ. Then, we provide a summary of the most prevalent prostate illnesses. Finally, we propose nutrition-based treatment in each of these prostate problems, based on in-depth research concerning its effects in this context, with an emphasis on surgery. Overall, we plead for an upgrade of this form of alternative treatment to a fully recognized mode of therapy for the prostate.

Hepatic fibrosis, a common pathological manifestation of chronic liver injury, is generally considered to be the end result of an increase in extracellular matrix produced by activated hepatic stellate cells (HSCs). The aim of the present study was to target the mechanisms underlying HSC activation in order to provide a powerful therapeutic strategy for the prevention and treatment of liver fibrosis. In the present study, a high‑throughput screening assay was established, and the histone deacetylase inhibitor givinostat was identified as a potent inhibitor of HSC activation in vitro . Givinostat significantly inhibited HSC activation in vivo , ameliorated carbon tetrachloride‑induced mouse liver fibrosis and lowered plasma aminotransferases. Transcriptomic analysis revealed the most significantly regulated genes in the givinostat treatment group in comparison with those in the solvent group, among which, dermokine (Dmkn), mesothelin (Msln) and uroplakin‑3b (Upk3b) were identified as potential regulators of HSC activation. Givinostat significantly reduced the mRNA expression of Dmkn , Msln and Upk3b in both a mouse liver fibrosis model and in HSC‑LX2 cells. Knockdown of any of the aforementioned genes inhibited the TGF‑β1‑induced expression of α‑smooth muscle actin and collagen type I, indicating that they are crucial for HSC activation. In summary, using a novel strategy targeting HSC activation, the present study identified a potential epigenetic drug for the treatment of hepatic fibrosis and revealed novel regulators of HSC activation.

Various nutrients have been designated as antioxidants, with a possible effect on diseases like cancer. This is partly due to their effect on prostaglandins, thereby affecting local pathological metabolic acidosis. This paper aims to summarize the culprit pathophysiological mechanisms involved, with a focus on the bone microenvironment. The omega- 6/omega-3 PUFA ratio is particularly investigated for its antioxidative effects, countering these pathways to fight the disease. This feature is looked at concerning its impact on health in general, with a particular focus on malignant bone metastasis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

As a major neurodevelopmental disorder, Autism Spectrum Disorder (ASD) encompasses deficits in communication and repetitive and restricted interests or behaviors in childhood and adolescence. Its etiology may come from either a genetic, epigenetic, neurological, hormonal, or an environmental cause, generating pathways that often altogether play a synergistic role in the development of ASD pathogenesis. Furthermore, the metabolic origin of ASD should be important as well. A balanced diet consisting of the essential and special nutrients, alongside the recommended caloric intake, is highly recommended to promote growth and development that withstand the physiologic and behavioral challenges experienced by ASD children. In this review paper, we evaluated many studies that show a relationship between ASD and diet to develop a better understanding of the specific effects of the overall diet and the individual nutrients required for this population. This review will add a comprehensive update of knowledge in the field and shed light on the possible nutritional deficiencies, metabolic impairments (particularly in the gut microbiome), and malnutrition in individuals with ASD, which should be recognized in order to maintain the improved socio-behavioral habit and physical health., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Many serious inflammatory disorders and nutrient deficiencies induce chronic pain, and anti-inflammatory diets have been applied successfully to modify the inflammatory symptoms causing chronic pain. Numerous scientific data and clinical investigations have demonstrated that long-term inflammation could lead to an inappropriate or exaggerated sensibility to pain. In addition, some Non-steroidal Anti-inflammatory Drugs (NSAID), which directly act on the many enzymes involved in pain and inflammation, including cyclooxygenases, are used to dampen the algesic signal to the central nervous system, reducing the responses of soft C-fibers to pain stimuli. On the other hand, there are a few reports from both health authorities and physicians, reporting that decreased transmission of pain signals can be achieved and improved, depending on the patient's dietary habit. Many nutrients, as well as a suitable level of exercise (resistance training), are the best methods for improving the total mitochondrial capacity in muscle cells, which can lead to a reduction in sensitivity to pain, particularly by lowering the inflammatory signaling to C-fibers. According to the current literature, it could be proposed that chronic pain results from the changed ratio of neuropeptides, hormones, and poor nutritional status, often related to an underlying inflammatory disorder. The current review also evaluates the effective role of nutrition-related interventions on the severity of chronic pain. This review pointed out that nutritional interventions can have a positive effect on pain experience through the indirect inhibitory effect on prostaglandin E2 and attenuation of mitochondrial dysfunction caused by ischemia/reperfusion in skeletal muscle, improving the intracellular antioxidant defense system. These data highlight the need for more nutrition studies where chronic pain is the primary outcome, using accurate interventions. To date, no nutritional recommendation for chronic pain has been officially proposed. Therefore, the goal of this article is to explore pain management and pain modulation, searching for a mode of nutrition efficient in reducing pain., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The present study aimed to assess the level of metal ions [chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), nickel (Ni), and zinc (Zn)] in the serum of patients with fixed orthodontic appliances. One hundred samples (32 males, 68 females) were collected from patients undergoing fixed orthodontic treatment for different periods. A reference (control) group (24 males, 16 females) who had no appliances was used to properly evaluate the changes in the level of these elements in orthodontic appliance users. The element concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS). Higher concentrations of metal ions (except for Cr) were found in the serum of the orthodontic group. Bivariate scatter plot showed a highly significant (p < 0.001) correlation between Ni and other elements. The duration of orthodontic treatment increased significantly the Ni levels whereas the bracket type was found to have no significant impact on altering the concentration level of metal ions. The results of the SEM-EDS showed a high variation in the level of metal ions in the brackets and wires. In conclusion, fixed orthodontic appliances increased serum levels of Ni, Zn, Mn, Fe, and Cu but did not change Cr levels.

Dietary habits are fundamental issues to assess when modulating health and well-being; however, different nutritional panels may help individuals prevent acute and chronic pain. Many substances, known to be active antioxidants and anti-inflammatory compounds, should serve this fundamental task. Antinociceptive and analgesic natural compounds include flavonoids, terumbone from ginger root, curcuminoids, ω-3 polyunsaturated fatty acids, and taurine. Furthermore, correct intake of trace elements and minerals is strategic to reduce inflammation-related pain. This review addresses these items in an effort to suggest new criteria for proper dietary supplementation to prevent pain., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To better define the rare adverse event (AE) of diabetes mellitus associated with immune checkpoint inhibitors (ICIs)., Design and Methods: We report the case of a lung cancer patient with diabetic ketoacidosis (DKA) and autoimmune thyroiditis during pembrolizumab treatment. We provide a systematic review of all published cases (PubMed/Web of Science/Cochrane, through November 2018) of autoimmune diabetes mellitus related to blockade of the cytotoxic T-lymphocyte antigen 4 (CTLA-4)-, programmed cell death 1 (PD-1) receptor or its ligand (PD-L1) or combination (ICI) therapy., Results: Our literature search identified 90 patient cases (our case excluded). Most patients were treated with anti-PD-1 or anti-PD-L1 as monotherapy (79%) or in combination with CTLA-4 blockade (15%). On average, diabetes mellitus was diagnosed after 4.5 cycles; earlier for combination ICI at 2.7 cycles. Early-onset diabetes mellitus (after one or two cycles) was observed during all treatment regimens. Diabetic ketoacidosis was present in 71%, while elevated lipase levels were detected in 52% (13/25). Islet autoantibodies were positive in 53% of patients with a predominance of glutamic acid decarboxylase antibodies. Susceptible HLA genotypes were present in 65% (mostly DR4). Thyroid dysfunction was the most frequent other endocrine AE at 24% incidence in this patient population., Conclusion: ICI-related diabetes mellitus is a rare but often life-threatening metabolic urgency of which health-care professionals and patients should be aware. Close monitoring of blood glucose and prompt endocrine investigation in case of hyperglycemia is advisable. Predisposing factors such as HLA genotype might explain why some individuals are at risk.

Objectives: Cachexia is an important outcome-modulating parameter in patients with cancer. In the context of a randomized controlled trial on cachexia and nutritional therapy, the TiCaCONCO (Tight Caloric Control in the Cachectic Oncologic Patient) trial, the contacts between patients with cancer and health care practitioners and oncologists were screened. The aim of this retrospective study was to identify in the charts the input of data on body weight (necessary to identify cachexia stage), relevant nutritional data, and nutritional interventions triggered or implemented by oncologists and dietitians., Methods: In a tertiary, university oncology setting, over a time span of 8 mo (34 wk), the charts of patients admitted to an oncology, gastroenterology, or abdominal surgery unit were screened for the presence of information contributing to a cancer cachexia diagnosis. Data (patient characteristics, tumor type, and location) was gathered., Results: We analyzed 9694 files. Data on body weight was present for >90% of patients. Of the 9694 screening, 118 new diagnoses of cancer were present (1.22% of patient contacts). Information on weight evolution or nutritional status was absent for 54 patients (46%). In contacts between oncologists and patients with cancer, at the time of diagnosis, cachexia was present in 50 patients (42%). In 7 of these patients (14%), no nutritional information was present in the notes. Of the 50 patients with cachexia, only 8 (16%) had a nutritional intervention initiated by the physician. Nutritional interventions were documented in the medical note in 11 patients (9%) in the overall study population. Dietitians made notes regarding nutrition and weight for 49 patients (42%). We could not demonstrate a difference in mortality between cachectic and non-cachectic patients, although numbers are small for analysis., Conclusion: Patients newly diagnosed with cancer are not systematically identified as being cachectic and if they are, interventions in the field of nutrition therapy are largely lacking. Important barriers exist between oncologists and dietitians, the former being mandatory to the success of a nutrition trial in cancer., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: An optimal nutritional approach sustained by convenient monitoring of metabolic status and reliable assessment of energy expenditure (EE) may improve the outcome of critically ill patients on extracorporeal membrane oxygenation (ECMO). We previously demonstrated the feasibility of indirect calorimetry (IC)-the standard of care technique to determine caloric targets-in patients undergoing ECMO. This study aims to compare measured with calculated EE during ECMO treatment. We additionally provide median EE values for use in settings where IC is not available., Methods: IC was performed in seven stable ECMO patients. Gas exchange was analyzed at the ventilator, and ECMO side and values were introduced in a modified Weir formula to calculate resting EE. Results were compared with EE calculated with the Harris-Benedict equation and with the 25 kcal/kg/day ESPEN recommendation., Results: Total median oxygen consumption rate was 196 (Q1-Q3 158-331) mL/min, and total median carbon dioxide production was 150 (Q1-Q3 104-203) mL/min. Clinically relevant differences between calculated and measured EE were observed in all patients. The median EE was 1334 (Q1-Q3 1134-2119) kcal/24 hours or 18 (Q1-Q3 15-27) kcal/kg/day., Conclusion: Compared with measured EE, calculation of EE both over- and underestimated caloric needs during ECMO treatment. Despite a median EE of 21 kcal/kg/day, large variability in metabolic rate was found and demands further investigation., (© 2018 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Along with playing an important role in circadian rhythm, melatonin is thought to play a significant role in preventing cells from damage, as well as in the inhibition of growth and in triggering apoptosis in malignant cells. Its relationship with circadian rhythms, energetic homeostasis, diet, and metabolism, is fundamental to achieve a better comprehension of how melatonin has been considered a chemopreventive molecule, though very few papers dealing with this issue. In this article, we tried to review the most recent evidence regarding the protective as well as the antitumoral mechanisms of melatonin, as related to diet and metabolic balance. From different studies, it was evident that an intracellular antioxidant defense mechanism is activated by upregulating an antioxidant gene battery in the presence of high-dose melatonin in malignant cells. Like other broad-spectrum antioxidant molecules, melatonin plays a vital role in killing tumor cells, preventing metastasis, and simultaneously keeping normal cells protected from oxidative stress and other types of tissue damage., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cancer-related Cachexia (CAC) is a syndrome occurring in many cancer patients, with a detrimental effect on their survival. Recent reports have outlined that the syndrome may be partly explained by the deleterious and pro-inflammatory action of Reactive Oxygen Species (ROS). This review focuses on nutrients that theoretically could counteract the oxidative stress in tumor cells, fundamentally due to their antioxidant activity. The preclinical and clinical results obtained with the nutritional elements selenium, melatonin, taurine, carnosine, coenzyme Q10 (ubiquinone), and omega-3 polyunsaturated fatty acids (PUFA's) are discussed in the light of the pathophysiology of CAC. This should indicate that they are viable candidates for the treatment of CAC, with the ultimate goal to promote patient survival. Combination therapy with diet modification added to the novel pharmaceutical agent ghrelin, a hormone with anti-inflammatory properties, represents a promising concept., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Chronic fatigue syndrome (CFS) is known as a multi-systemic and complex illness, which induces fatigue and long-term disability in educational, occupational, social, or personal activities. The diagnosis of this disease is difficult, due to lacking a proper and suited diagnostic laboratory test, besides to its multifaceted symptoms. Numerous factors, including environmental and immunological issues, and a large spectrum of CFS symptoms, have recently been reported. In this review, we focus on the nutritional intervention in CFS, discussing the many immunological, environmental, and nutritional aspects currently investigated about this disease. Changes in immunoglobulin levels, cytokine profiles and B- and T- cell phenotype and declined cytotoxicity of natural killer cells, are commonly reported features of immune dysregulation in CFS. Also, some nutrient deficiencies (vitamin C, vitamin B complex, sodium, magnesium, zinc, folic acid, l-carnitine, l-tryptophan, essential fatty acids, and coenzyme Q 10 ) appear to be important in the severity and exacerbation of CFS symptoms. This review highlights a far-driven analysis of mineral and vitamin deficiencies among CFS patients., (Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background & Aims: Malnutrition is widespread among cardiac surgery patients and is independently related to an adverse postoperative evolution or outcome. We aimed to assess whether nutrition therapy (NT) could alter caloric deficit, morbidity, and mortality in patients scheduled for non-emergency coronary artery bypass graft (CABG) or aortic valve surgery., Methods: 351 patients undergoing either elective CABG or aortic valve surgery were studied. Patients receiving NT were enrolled from January 2013 until December 2014. A retrospective control group (CT) consisted of 142 matched patients. The primary endpoint was to evaluate whether NT could limit caloric deficit (Intake to Need Deviation). Secondary endpoints addressed the potential effect of NT on morbidity and mortality. Patients were followed for one year after surgery., Results: There was no significant difference in patient, laboratory or mortality profile between the groups. Caloric deficit could be limited in the intervention group, essentially by providing oral feeding and oral supplements. A minority of patients required enteral or parenteral nutrition during their hospital stay. Caloric deficit increased after the second postoperative day because more patients were switched to oral feeding and intravenous infusions were omitted. Combining CABG and aortic valve surgery, male patients in the NT group had significantly less arrhythmia than in the CT group (7% versus 31%; P = 0.0056), while females in the NT group had significantly less pneumonia than in the CT group (7% versus 22%; P = 0.0183). Survival was significantly higher in female NT patients compared to CT patients, both for CABG (100% versus 83%; P = 0.0015) and aortic valve surgery (97% versus 78%; P = 0.0337)., Conclusion: The results suggest that NT beneficially affects morbidity and mortality in elective cardiac surgery patients. The impact of NT seems more pronounced in women than in men. Registration: Clinicaltrials.gov: NCT02902341., (Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background & Aims: Sweetening agents are sugar substitutes with a low glycemic index, used to obtain a better glycemic control in diabetes patients. However, they also may have a role in other subjects, as a high glycemic index is thought to cause many pathological conditions. Unfortunately, not all artificial sweeteners are perceived as sweet as sugar by patients. Consumers refer often to an after taste present in foods sweetened with intensive sweeteners. The objective of this study was to explore whether Zùsto ® had a low glycemic index, to replace glucose as a sweetener., Methods: In this study, the glycemic index (GI) of a new sweetening agent, Zùsto ® , is compared to that of glucose 25 g, a standard sugar-loaded drink used in the oral glucose tolerance test to detect diabetes, as primary endpoint. Zùsto ® is composed of non-digestible, water soluble fibers and sweeteners. 10 healthy, female non-obese volunteers received glucose and Zùsto ® , albeit by an interval of a week. Evolution of glycemia, C-peptide and insulin release was measured at different time-points after intake., Results: The results show that, when calculating the mean incremental Area Under the Curve (AUC), the AUC of glucose was around five times as high as that of Zùsto ® ; a GI of 22 for Zùsto ® was calculated. Furthermore, Zùsto ® had no significant effect on the glycemia, contrary to glucose, for at least 60'. This was also the case concerning C-peptide and insulin release, but the difference lasted even for 180'. Moreover, Zùsto ® was perceived as sweet by all volunteers, with no particular aftertaste., Conclusion: Zùsto ® could be a viable alternative for fast sugars and other sweetening agents, both for diabetic patients and other subjects, requiring however a larger trial to confirm these results. CLINICALTRIALS.GOV: NCT02607345., (Copyright © 2017 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: Cancer is a common disease and many patients are diagnosed with advanced stages. Due to cancer generalization, patients may become ill-nourished and even cachectic. Malignancy-related cachexia is associated with worsening physical function, reduced tolerance to anticancer therapy and increased mortality. We assessed the effect of a patient-tailored nutritional approach in newly discovered, treatment-naive cancer patients with cachexia., Methods: In a randomized, single-blinded, controlled pilot study, patients were treated with either intensive, biometric parameter-oriented dietary counseling (nutrition therapy) compared to regular dietary counseling (control), before and during conventional cancer treatment. Twenty patients were enrolled over a one-year period, 10 receiving nutrition therapy and 10 controls. The primary endpoint was recovery of body composition after nutrition therapy. Secondary endpoints declined in morbidity and mortality with nutrition therapy., Results: Average weight evolution in the control group after 3, 6 and 12 months was 0.19 ± 7.87 kg, -9.78 ± 7.00 kg and -5.8 kg, and in the nutrition therapy group 0.69 ± 2.4 kg, 0.77 ± 2.58 kg and 1.29 ± 3.76 kg. Control patients had a significantly longer average hospital stay than subjects from the nutrition therapy group (37.6 vs. 3.4 days). Eight nutrition therapy patients and 1 control patient were still alive after 2 years., Conclusions: Nutrition therapy based on patient-specific biophysical parameters helps to maintain body weight and induces a more optimal nutritional balance in cachectic cancer patients. Moreover, survival in cancer patients improved when their nutritional status, even partially, ameliorated., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The signal transducer and activator of transcription 3 (STAT3) can be activated by the tyrosine kinase domain of the chimeric protein nucleophosmin/anaplastic lymphoma kinase (NPM/ALK), and has a pivotal role in mediating NPM/ALK-related malignant cell transformation. Although the role of STAT3 and wild-type NPM in oncogenesis has been extensively investigated, the relationship between both molecules in cancer remains poorly understood. In the present study, we first demonstrate that STAT3 phosphorylation at tyrosine 705 is accompanied by a concomitant increase in the expression level of NPM. Nuclear co-translocation of phosphorylated STAT3 with NPM can be triggered by interferon-alpha (IFN-α) stimulation of Jurkat cells and phosphorylated STAT3 co-localizes with NPM in cancer cells showing constitutive STAT3 activation. We further demonstrate that STAT3 phosphorylation can transcriptionally mediate NPM upregulation in IFN-α-stimulated Jurkat cells and is responsible for maintaining its expression in cancer cells showing constitutive STAT3 activation. Inhibition of STAT3 phosphorylation or knockdown of NPM expression abrogates their simultaneous transnuclear movements. Finally, we found evidence for a physical interaction between NPM and STAT3 in conditions of STAT3 activation. In conclusion, NPM is a downstream effector of the STAT3 signaling, and can facilitate the nuclear entry of phosphorylated STAT3. These observations might open novel opportunities for targeting the STAT3 pathway in cancer.

The release of cytokines by T cells strongly defines their functional activity in vivo. The ability to produce multiple cytokines has been associated with beneficial immune responses in cancer and infectious diseases, while their progressive loss is associated with T-cell exhaustion, senescence and anergy. Consequently, strategies that enhance the multifunctional status of T cells are a key for immunotherapy. Dendritic cells (DCs) are professional antigen presenting cells that regulate T-cell functions by providing positive and negative co-stimulatory signals. A key negative regulator of T-cell activity is provided by binding of programmed death-1 (PD-1) receptor on activated T cells, to its ligand PD-L1, expressed on DCs. We investigated the impact of interfering with PD-L1/PD-1 co-stimulation on the multifunctionality of T cells, by expression of the soluble extracellular part of PD-1 (sPD-1) or PD-L1 (sPD-L1) in human monocyte-derived DCs during antigen presentation. Expression, secretion and binding of these soluble molecules after mRNA electroporation were demonstrated. Modification of DCs with sPD-1 or sPD-L1 mRNA resulted in increased levels of the co-stimulatory molecule CD80 and a distinct cytokine profile, characterized by the secretion of IL-10 and TNF-α, respectively. Co-expression in DCs of sPD-1 and sPD-L1 with influenza virus nuclear protein 1 (Flu NP1) stimulated Flu NP1 memory T cells, with a significantly higher number of multifunctional T cells and increased cytokine secretion, while it did not induce regulatory T cells. These data provide a rationale for the inclusion of interfering sPD-1 or sPD-L1 in DC-based immunotherapeutic strategies.

Regulatory T cells (Tregs) counteract anticancer immune responses through a number of mechanisms, limiting dendritic cell (DC)-based anticancer immunotherapy. In this study, we investigated the influence of various DC activation stimuli on the Treg functionality. We compared DCs activated by electroporation with mRNA encoding constitutively active TLR4 (caTLR4) and CD40 ligand (DiMix-DCs), or these factors together with mRNA encoding the costimulatory molecule CD70 (TriMix-DCs) with DCs maturated in the presence of a mixture of inflammatory cytokines (DCs maturated with a combination of the cytokines IL-1β, IL-6, TNF-α, and PGE2) for their ability to counteract Tregs on different levels. We first demonstrated that there was no difference in the extent of Treg induction starting from CD4(+)CD25(-) T cells under the influence of the different DC maturation stimuli. Second, we showed that both DiMix- and TriMix-DCs could partly alleviate Treg inhibition of CD8(+) T cells. Third, we observed that CD8(+) T cells that had been precultured with DiMix-DCs or TriMix-DCs were partially protected against subsequent Treg suppression. Finally, we showed that Tregs cocultured in the presence of TriMix-DCs, but not DiMix-DCs, partially lost their suppressive capacity. This was accompanied by a decrease in CD27 and CD25 expression on Tregs, as well as an increase in the expression of T-bet and secretion of IFN-γ, TNF-α, and IL-10, suggesting a shift of the Treg phenotype toward a Th1 phenotype. In conclusion, these data suggest that TriMix-DCs are not only able to suppress Treg functions, but moreover could be able to reprogram Tregs to Th1 cells under certain circumstances.