New Inoculation Strategy for Legume Based on Rhizobium-Metabolite Co-encapsulation.

The new strategies that are trying to be developed to protect microorganisms for a successful application have generated various types of granulated, powdered, or liquid formulations. In this work, we have developed a rhizobial encapsulation system for legumes accompanied by metabolites to enhance microorganism-plant communication. This novel way of producing a biofertilizer for legumes was developed based on alginate, a degradable compound that allows environmentally friendly use. This way of generating an inoculant allows it designing by making different molecular combinations for different purposes, being a double inoculant, biological and molecular.

Predictive factors of problematic smartphone use in young Spanish university students.

Smartphones have evolved from being a helpful tool in our days to be an indispensable complement. Its presence in our daily lives has grown to reach a problematic use on occasions. This fact is even more remarkable when we speak of young adults and adolescents, in which problematic situations can be identified as derived from its use. In this study, we analyze the self-perception of 409 young adults pursuing an Education university degree on the use and consumption of the smartphone via their responses to the Mobile Phone Problem Use Scale. The results show that, despite not perceiving the use of the mobile phone as problematic, some of the behaviors described by them as habitual would imply inappropriate use of the smartphone. Some outlined by the sample included mitigating loneliness, fear of isolation, or using it to feel better. Surprisingly, these are not recognized as problematic, despite being some of the most apparent indicators of misuse. The analysis of the results shows how younger populations and, mainly women, present this type of worrying and unconscious behavior. However, the increasing use of these devices within training areas offer new options to favor its proper use, mitigating the possible adverse effects of its use.

Evolution of Posttraumatic Symptoms and Related Factors in Healthcare Workers During the COVID-19 Pandemic: A Longitudinal Study.

OBJECTIVE: This study aimed to (1) evaluate the evolution of mental health (posttraumatic stress symptoms [PTSSs], depression, and burnout) of healthcare workers during the second wave of the pandemic (November to December 2020) and compare it with the first wave (March to May 2020), and (2) ascertain the predictors of PTSSs. METHODS: In March to May 2020 (T1), 269 healthcare professionals working in Spain completed PTSSs, sadness, resilience, and coping questionnaires. In November to December 2020 (T2, N = 58), we assessed PTSSs, sadness, burnout, and depression. RESULTS: Among the healthcare professionals, 63.8% displayed severe PTSSs, 51.7% depressive symptoms, and 79.3% emotional exhaustion (T2). Some risk factors were caring for patients who were severely ill or dying and using rumination, thinking avoidance, self-isolation, emotional expression, and self-blaming as coping strategies. CONCLUSIONS: The pandemic has had a deep and long-lasting impact on the healthcare workers' mental health.

[Eating disorders and obesity in adolescents: Another challenge of our times]. / Trastornos de la conducta alimentaria y obesidad en adolescentes: Otro desafío de nuestros tiempos.

Obesity (OB) and feeding and eating disorders (FED) are complex and prevalent pathologies in ado lescents. OB has been shown to be a risk factor for developing binge eating disorder and bulimia nervosa, and vice versa, these FED also develop OB. However, obese adolescents may present atypical or sub-threshold criteria for FED. The objective of this review is to describe the epidemiological, cli nical, and therapeutic relationship between FED and OB in adolescents, with emphasis on the urgent need for research and collaboration among professionals in the fields of mental health and nutrition.

Estenosis acueductal en acondroplasia: a propósito de un caso / Aqueductal Stenosis in Achondroplasia: a Clinical Case Report

Resumen: La acondroplasia es la condición asociada a talla baja desproporcionada más frecuente, caracterizada por un crecimiento óseo anormal, que resulta en talla baja con extremidades cortas e inteligencia normal. Una de las complicaciones más habituales es la compresión medular, que puede ocurrir a cualquier nivel, siendo más frecuente en la unión cráneo cervical, generando alta morbimortalidad en los primeros años de vida, principalmente por muerte súbita. Presentamos una paciente de 1 año 10 meses con diagnóstico precoz de acondroplasia, que presentó en su evolución estenosis acueductal con compresión medular, sintomática, pesquisada en control rutinario, que requirió cirugía descompresiva con buena evolución posterior. Palabras clave: Acondroplasia, estenosis acueductal, compresión medular sintomática, hidrocefalia, craniectomía suboccip

Achondroplasia is the most frequent cause of disproportionate short stature, it is characterized by abnormal growth of long bones, rendering a short-limbed individual of normal intelligence. A serious potential complication is spinal compression, which can happen at any level but is particularly common at the craniocervical junction. It can cause important morbidity during the first few years of life, including sudden death. We present a 22-monthold patient diagnosed with achondroplasia, who developed aqueductal stenosis with symptomatic spinal cord compression, diagnosed during a routine consultation, requiring decompressive surgery with excellent results. Key words: Achondroplasia, aqueductal stenosis, symptomatic spinal cord compression, hydrocephalus, suboccipital craniectomy.

Effects of Oral Administration of Silymarin in a Juvenile Murine Model of Non-alcoholic Steatohepatitis.

The increasing prevalence of non-alcoholic fatty liver disease (NAFLD) in adolescents is challenging the global care system. No therapeutic strategies have been defined so far, and changes in the lifestyle remain the only alternative. In this study, we assessed the protective effects of silymarin in a juvenile non-alcoholic steatohepatitis (NASH) model and the in vitro effects on fat-laden human hepatocytes. C57Bl/6 mice were exposed to HFHC diet immediately after weaning. After eight weeks, animals showed histological signs of NASH. Silymarin was added to the HFHC diet, the treatment continued for additional 12 weeks and the effects on BMI, hepatomegaly, visceral fat, lipid profile, transaminases, HOMA-IR, steatosis, inflammation, fibrosis, oxidative stress, and apoptosis were determined. The switch from HFHC to control diet was used to mimic life style changes. In vitro experiments were performed in parallel in human hepatocytes. HFHC diet supplemented with silymarin showed a significant improvement in glycemia, visceral fat, lipid profile, and liver fibrosis. Moreover, it reduced (both in vitro and in vivo) ALT, hepatic inflammation, oxidative stress, and apoptosis. Lifestyle changes restored the control group parameters. The data presented show the beneficial effects of the oral administration of silymarin in the absence of changes in the dietary habits in a juvenile model of NASH.

Hepatocyte-derived macrophage migration inhibitory factor mediates alcohol-induced liver injury in mice and patients.

BACKGROUND & AIMS: Macrophage migration inhibitory factor (MIF) is a multi-potent cytokine that contributes to the inflammatory response to injury. MIF is expressed by multiple cell types; however, the cellular source and actions of MIF in alcoholic liver disease (ALD) are not well known. Here we tested the hypothesis that non-myeloid cells, specifically hepatocytes, are an important cellular source of MIF in ALD. METHODS: MIF expression was measured in HuH7 and differentiated THP-1 cells in response to ethanol. Ethanol-induced liver injury was assessed in C57BL/6 (WT) and Mif-/- bone marrow chimeras. MIF was measured in peripheral and suprahepatic serum, as well as visualized by immunohistochemistry in liver biopsies, from patients with alcoholic hepatitis (AH). RESULTS: HuH7 hepatocytes, but not THP-1 macrophages, released MIF in response to ethanol challenge in culture. In chimeric mice expressing MIF in non-myeloid cells (Mif-/-→WT), chronic ethanol feeding increased ALT/AST, hepatic steatosis, and expression of cytokine/chemokine mRNA. In contrast, chimeric mice not expressing MIF in non-myeloid cells (WT→Mif-/-) were protected from ethanol-induced liver injury. Immunohistochemical staining of liver biopsies from patients with AH revealed a predominant localization of MIF to hepatocytes. Interestingly, the concentration of MIF in suprahepatic serum, but not peripheral serum, was positively correlated with clinical indicators of disease severity and with an increased risk of mortality in patients with AH. CONCLUSIONS: Taken together, these data provide evidence that hepatocyte-derived MIF is critical in the pathogenesis of ALD in mice and likely contributes to liver injury in patients with AH. Lay summary: Alcoholic liver disease is a major cause of preventable mortality worldwide, and lacks specific pharmacological therapies. Recent studies have recognized that macrophage migration inhibitor factor (MIF) has a critical role in the inflammatory response to liver damage. However, the cells that produce this protein are still unknown. Our present findings reveal that hepatocytes, the main cell type in the liver, are primarily responsible for MIF production in response to alcohol, which promotes liver injury. Our study suggests that drugs inhibiting MIF production could be beneficial in treating patients with liver disease due to excessive alcohol consumption.

Keypress-Based Musical Preference Is Both Individual and Lawful.

Musical preference is highly individualized and is an area of active study to develop methods for its quantification. Recently, preference-based behavior, associated with activity in brain reward circuitry, has been shown to follow lawful, quantifiable patterns, despite broad variation across individuals. These patterns, observed using a keypress paradigm with visual stimuli, form the basis for relative preference theory (RPT). Here, we sought to determine if such patterns extend to non-visual domains (i.e., audition) and dynamic stimuli, potentially providing a method to supplement psychometric, physiological, and neuroimaging approaches to preference quantification. For this study, we adapted our keypress paradigm to two sets of stimuli consisting of seventeenth to twenty-first century western art music (Classical) and twentieth to twenty-first century jazz and popular music (Popular). We studied a pilot sample and then a separate primary experimental sample with this paradigm, and used iterative mathematical modeling to determine if RPT relationships were observed with high R2 fits. We further assessed the extent of heterogeneity in the rank ordering of keypress-based responses across subjects. As expected, individual rank orderings of preferences were quite heterogeneous, yet we observed mathematical patterns fitting these data similar to those observed previously with visual stimuli. These patterns in music preference were recurrent across two cohorts and two stimulus sets, and scaled between individual and group data, adhering to the requirements for lawfulness. Our findings suggest a general neuroscience framework that predicts human approach/avoidance behavior, while also allowing for individual differences and the broad diversity of human choices; the resulting framework may offer novel approaches to advancing music neuroscience, or its applications to medicine and recommendation systems.

An Animal Model for the Juvenile Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis.

Non Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) are the hepatic manifestations of the metabolic syndrome; worrisome is the booming increase in pediatric age. To recreate the full spectrum of juvenile liver pathology and investigate the gender impact, male and female C57Bl/6 mice were fed with high fat diet plus fructose in the drinking water (HFHC) immediately after weaning (equal to 3-years old human), and disease progression followed for 16 weeks, until adults (equal to 30-years old human). 100% of subjects of both genders on HFHC diet developed steatosis in 4weeks, and some degree of fibrosis in 8weeks, with the 86% of males and 15% of females presenting a stage 2 fibrosis at 16weeks. Despite a similar final liver damage both groups, a sex difference in the pathology progression was observed. Alterations in glucose homeostasis, dyslipidemia, hepatomegaly and obese phenotype were evident from the very beginning in males with an increased hepatic inflammatory activity. Conversely, such alterations were present in females only at the end of the HFHC diet (with the exception of insulin resistance and the hepatic inflammatory state). Interestingly, only females showed an altered hepatic redox state. This juvenile model appears a good platform to unravel the underlying gender dependent mechanisms in the progression from NAFLD to NASH, and to characterize novel therapeutic approaches.

Determining optimal pattern sequences for three-dimensional structured light sensory systems.

Structured light (SL) techniques are used for three-dimensional (3D) measurements of objects in a wide variety of applications. SL-based sensory systems obtain the 3D surface profile of an object from the deformation of light patterns projected onto the object of interest. The number of fringes used in the projected light patterns has a direct effect on the 3D reconstruction errors. This paper presents a novel methodology for determining the optimal sequence of multi-fringe patterns that minimizes reconstruction errors caused by random noise. Experiments conducted with a variety of objects as well as a comparison study demonstrate the effectiveness of the proposed methodology.

The Pros and the Cons for the Use of Silybin-Rich Oral Formulations in Treatment of Liver Damage (NAFLD in Particular).

The increasing prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) worldwide is becoming a challenge for the modern global care system. The lipotoxic process is characterized by an oxidative stress followed by a burst of the inflammatory response, prompting the wound healing process (fibrosis), which can ultimately lead to the development of cirrhosis and the subsequent complications. There is no consensus concerning an effective pharmacological treatment. Therefore, there is a need for effective therapeutic compounds. Silibinin the major active compound of Milk Thistle may be a potential candidate mainly due to its anti-oxidant, anti-inflammatory, and anti-fibrotic properties. In spite of the large number of data obtained in experimental models, the translation of the evidence in clinical setting is far to be conclusive. The aim of this paper is to critically review the aspects of the use of the different formulations of Silibinin in several experimental and clinical settings and to provide hints on the needed future studies.

The importance of the interaction between hepatocyte and hepatic stellate cells in fibrogenesis induced by fatty accumulation.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease is characterized by an initial accumulation of triglycerides that can progress to non-alcoholic steatohepatitis, which can ultimately evolve to cirrhosis and hepatocellular carcinoma. Hepatic stellate cells play a key role in liver fibrogenesis by an increased activation and an altered profile of genes involved in the turnover of extracellular matrix components. To reproduce in-vitro the functional cell connections observed in vivo it is essential to consider cell-to-cell proximity and interaction. The aim of this study was to determine the response to free fatty acids in a simultaneous co-culture model of hepatocytes and hepatic stellate cells. METHODS: Simultaneous co-culture model and monoculture of each cell type (control) were exposed to FFA for 24 up to 144 h. Quantification of steatosis; stellate cell activation; assessment of fibrogenic response; expression and activity of metalloproteinases as well as collagen biosynthesis were evaluated. RESULTS: Free fatty acids induced comparable steatosis in simultaneous co-culture and monoculture. However, the activation of the stellate cells assessed by alpha-smooth muscle actin expression is greater when cells were in close contact. Furthermore, a time-dependent increment of tissue inhibitor metalloproteinase-2 protein was observed, which was inversely correlated with protein expression and activity of matrix-metalloproteinases, suggesting enhanced collagen biosynthesis. This behavior was absent in cell monoculture. CONCLUSIONS: These data indicate that cell-to-cell proximity between hepatocytes and stellate cells is necessary for the initiation of the fibrotic process.

Riesgo de trastornos alimentarios en adolescentes obesos de la Región Metropolitana / Eating disorders risk among obese adolescents

Background: Preliminary research suggests that eating disorders (ED) are common among overweight teenagers. Missing the diagnosis is a poor prognostic factor. Aim: To quantify the risk of ED and the effects of age, sex and severity of obesity in obese adolescents. Patients and Methods: We studied 99 obese adolescents with a body mass index (BMI) > percentile 95 of CDC-NCHS, 51% females, aged between 11 and 19 years, attending an obesity clinic. The Eating Disorders Inventory-2 (EDI-2) was used to evaluate the risk of ED. A score equal or higher than 110, corresponding to the 85th percentile, was considered as risky. Results: Sixteen percent of studied adolescents had EDI scores > 110. No statistically significant differences were observed by age, sex or severity of obesity. EDI-2 scores in participants with a BMI z score over and under 4 were 93.6 ± 33.9 and 78.2 ± 38.8 respectively (p = 0.02). A high percentage of participants had body dissatisfaction (BD) and drive for thinness. Bulimic symptoms, inefficacy, fear of maturity, and impulsivity scores were significantly higher among participants with a high risk of developing ED. Conclusions: Obese adolescents have a high risk for ED, regardless of their age and sex. The risk increases along with higher BMI. The routine use of screening tests is fundamental for an early detection of ED.

[Eating disorders risk among obese adolescents]. / Riesgo de trastornos alimentarios en adolescentes obesos de la Región Metropolitana.

BACKGROUND: Preliminary research suggests that eating disorders (ED) are common among overweight teenagers. Missing the diagnosis is a poor prognostic factor. AIM: To quantify the risk of ED and the effects of age, sex and severity of obesity in obese adolescents. PATIENTS AND METHODS: We studied 99 obese adolescents with a body mass index (BMI) > percentile 95 of CDC-NCHS, 51% females, aged between 11 and 19 years, attending an obesity clinic. The Eating Disorders Inventory-2 (EDI-2) was used to evaluate the risk of ED. A score equal or higher than 110, corresponding to the 85th percentile, was considered as risky. RESULTS: Sixteen percent of studied adolescents had EDI scores > 110. No statistically significant differences were observed by age, sex or severity of obesity. EDI-2 scores in participants with a BMI z score over and under 4 were 93.6 ± 33.9 and 78.2 ± 38.8 respectively (p = 0.02). A high percentage of participants had body dissatisfaction (BD) and drive for thinness. Bulimic symptoms, inefficacy, fear of maturity, and impulsivity scores were significantly higher among participants with a high risk of developing ED. CONCLUSIONS: Obese adolescents have a high risk for ED, regardless of their age and sex. The risk increases along with higher BMI. The routine use of screening tests is fundamental for an early detection of ED.

Functional ruthenium(II)- and iridium(III)-containing polymers for potential electro-optical applications.

The need for novel materials with luminescent properties and advanced processing features requires reliable and reproducible synthetic routes for the design of suitable materials, such as e.g. polypyridyl ruthenium(II) and iridium(III)-containing polymers. The most popular ligand for those purposes is the 4,4'-functionalized bipyridine unit. Therefore, several synthetic strategies for the derivatization of the 4,4'-dimethyl-2,2'-bipyridine are highlighted, and in particular functionalities, which enable further covalent linkage to polymeric structures, are discussed in this critical review. Subsequently, the different synthetic strategies for the preparation of polymeric metal-complexes are described, either starting from small functionalized complexes (later covalently attached to the polymer), or from macroligands (subsequently coordinated to the metal ions). The designed materials reveal good processing properties using spin coating and inkjet printing, as well as beneficial electro-optical properties for potential thin functional film applications, such as light-emitting electrochemical cells.

Control of cellular senescence by CPEB.

Cytoplasmic polyadenylation element-binding protein (CPEB) is a sequence-specific RNA-binding protein that promotes polyadenylation-induced translation. While a CPEB knockout (KO) mouse is sterile but overtly normal, embryo fibroblasts derived from this mouse (MEFs) do not enter senescence in culture as do wild-type MEFs, but instead are immortal. Exogenous CPEB restores senescence in the KO MEFs and also induces precocious senescence in wild-type MEFs. CPEB cannot stimulate senescence in MEFs lacking the tumor suppressors p53, p19ARF, or p16(INK4A); however, the mRNAs encoding these proteins are unlikely targets of CPEB since their expression is the same in wild-type and KO MEFs. Conversely, Ras cannot induce senescence in MEFs lacking CPEB, suggesting that it may lie upstream of CPEB. One target of CPEB regulation is myc mRNA, whose unregulated translation in the KO MEFs may cause them to bypass senescence. Thus, CPEB appears to act as a translational repressor protein to control myc translation and resulting cellular senescence.

Total carnitine and acylated carnitine ratio: relationship of free carnitine with lipid parameters in pediatric dialysis patients.

Carnitine has an essential role in the mitochondrial oxidation of long-chain fatty acids. Carnitine deficiency has been described in patients with chronic kidney disease. Total carnitine (TC) deficiency or a lower-than-normal ratio of free carnitine to acylated carnitine (FC:AC) has been shown to be associated with disorders in metabolism and plasma lipids. Metabolism and therapeutic use of carnitine have therefore been a major area of interest in dialysis patients. In a prospective observational study, we determined carnitine status (TC and FC:AC) and its correlations with lipid plasma levels in peritoneal dialysis (PD) and hemodialysis (HD) patients. In pediatric patients on chronic PD or HD, we evaluated nutritional status (weight and height), biochemical parameters (TC, FC, and AC levels), and fasting plasma lipoprotein concentrations. We studied 35 patients (16 boys, 19 girls; 25 on PD, 10 on HD). Median age was 5 years (range: 3 months-15 years). Median weight-to-height Z-score was -0.5 (range: -2.1 to 1.9), and median height-to-age Z-score was -2.5 (range: -0.3 to -2.9). The mean TC was 65.4 +/- 23.8 pg/mL (normal value: 40-55 pg/mL); the median AC was 18 pg/mL (range: 2-56pg/mL; normal value: 3-15 pg/mL); and the mean FC was 41.8 +/- 16.6 pg/mL (normal value: 25-35 pg/mL). Median serum FC:AC was 2.22 (range: 0.59-4.3; normal value: 4). A significantly higher AC and a lower FC:AC were observed in HD patients as compared with PD patients. No differences in TC and FC were observed when patients were grouped by dialysis modality, time on dialysis, or nutrition status. Total cholesterol was 200 mg/dL or higher in 20 patients, and 25 patients showed elevated triglycerides (> 150 mg/dL). The latter patients had a higher AC than did the group of patients with triglycerides below 150 mg/dL (AC: 22 pg/mL and 12.5 pg/mL respectively; Kruskal-Wallis p < 0.003). We found TC levels to be high in this group of patients. However, the FC:AC ratio was lower than normal in all except in 1 patient. Elevated triglycerides were associated with elevated AC, suggesting carnitine insufficiency in our patients.

Controlled study of enteral arginine supplementation in burned children: impact on immunologic and metabolic status.

OBJECTIVE: We compared the effects of an arginine-supplemented diet with those of an isocaloric isonitrogenous diet on immune and metabolic response of children with burns. METHODS: This was a double-blind, randomized, placebo-controlled trial in a burn treatment center of a pediatric hospital in Santiago, Chile. All children (1-5 y of age) admitted within 48 h of a moderate to deep burn injury covering 10% to 40% of total body surface area were evaluated. Twenty-eight children met the criteria and were randomly assigned to receive an arginine-supplemented diet (AG; n = 14) or an isocaloric isonitrogenous diet (CG; control, n = 14) for 14 d. Samples were collected at admission (baseline) and on days 7 and 14 for lymphoproliferative response to mitogens, plasma interleukins (interleukin-1, interleukin-6, tumor necrosis factor-alpha), plasma arginine and ornithine levels, serum C-reactive protein, prealbumin, albumin, glucose, and total urinary nitrogen. RESULTS: The AG enhanced lymphoproliferative responses (analysis of variance, P < 0.05), which were 72% of normal at baseline in both groups; by day 7 responses increased to 144% in the AG group and decreased to 56% in the CG group; both groups returned to normal by day 14. Baseline interleukin-6 was significantly increased in all children. There were no differences in plasma concentrations of interleukin-1, interleukin-6, tumor necrosis factor-alpha, C-reactive protein, prealbumin, albumin, or glucose between the AG and CG groups. On day 7 plasma ornithine levels increased significantly in the AG versus CG group (P < 0.05); arginine levels showed no change. CONCLUSIONS: An exclusively AG improves mitogen-stimulated lymphocyte proliferation in burned children. The benefits of arginine for the immune system do not appear to be related to a metabolic response. The biological significance of this finding remains to be determined.

Light-emitting iridium(III) and ruthenium(II) polypyridyl complexes containing quadruple hydrogen-bonding moieties.

A novel compound containing both a 2,2'-bipyridine as well as a 2-ureido-4[1H]-ureidopyrimidinone supramolecular moiety (3) has been synthesised and fully characterized by 1H-NMR, MALDI-TOFMS, UV-vis and IR spectroscopy. Subsequent coordination to iridium and ruthenium polypyridyl precursors allowed the formation of iridium(III) and ruthenium(II) polypyridyl dimers (5 and 7) assembled via quadruple hydrogen-bonding as well as metal coordination interactions. The syntheses and complete characterization of these materials by means of two-dimensional NMR techniques (1H-1H COSY and 1H-1H DOSY) as well as IR and MALDI-TOFMS are described in detail. Comparative studies of the optical properties of the luminescent model complexes (5' and '7) and the dimer species (5 and 7) are also illustrated. In addition, good processability of the materials has been demonstrated by inkjet printing leading to thin films revealing their potential for light-emitting devices.

Intratumoural administration of dendritic cells: hostile environment and help by gene therapy.

Like paratroopers in special operations, dendritic cells (DCs) can be deployed behind the enemy borders of malignant tissue to ignite an antitumour immune response. 'Cross-priming T cell responses' is the code name for their mission, which consists of taking up antigen from transformed cells or their debris, migrating to lymphoid tissue ferrying the antigenic cargo, and meeting specific T cells. This must be accomplished in such an immunogenic manner that specific T lymphocytes would mount a robust enough response as to fully reject the malignancy. To improve their immunostimulating activity, local gene therapy can be very beneficial, either by transfecting DCs with genes enhancing their performance, or by preparing tumour tissue with pro-inflammatory mediators. In addition, endogenous DCs from the tumour host can be attracted into the malignant tissue following transfection of certain chemokine genes into tumour cells. On their side, tumour stroma and malignant cells set up a hostile immunosuppressive environment for artificially released or attracted DCs. This milieu is usually rich in transforming growth factor-beta, vascular endothelial growth factor, and IL-10, -6 and -8, among other substances that diminish DC performance. Several molecular strategies are being devised to interfere with the immunosuppressive actions of these substances and to further enhance the level of anticancer immunity achieved after artificial release of DCs intratumourally.