Triglyceride to HDL Cholesterol Ratio for the Identification of MASLD in Obesity: A Liver Biopsy-Based Case-Control Study.

Associations between dyslipidemia and metabolic dysfunction-associated steatotic liver disease (MASLD) have been reported. Previous studies have shown that the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio may be a surrogate marker of MASLD, assessed by liver ultrasound. However, no studies have evaluated the utility of this ratio according to biopsy-proven MASLD and its stages. Therefore, our aim was to evaluate if the TG/HDL-C ratio allows for the identification of biopsy-proven MASLD in patients with obesity. We conducted a case-control study in 153 patients with obesity who underwent metabolic surgery and had a concomitant liver biopsy. Fifty-three patients were classified as no MASLD, 45 patients as metabolic dysfunction-associated steatotic liver-MASL, and 55 patients as metabolic dysfunction-associated steatohepatitis-MASH. A receiver operating characteristic (ROC) analysis was performed to assess the accuracy of the TG/HDL-C ratio to detect MASLD. We also compared the area under the curve (AUC) of the TG/HDL-C ratio, serum TG, and HDL-C. A higher TG/HDL-C ratio was observed among patients with MASLD, compared with patients without MASLD. No differences in the TG/HDL-C ratio were found between participants with MASL and MASH. The greatest AUC was observed for the TG/HDL-C ratio (AUC 0.747, p < 0.001) with a cut-off point of 3.7 for detecting MASLD (sensitivity = 70%; specificity = 74.5%). However, no statistically significant differences between the AUC of the TG/HDL-C ratio and TG or HDL-C were observed to detect MASLD. In conclusion, although an elevated TG/HDL-C ratio can be found in patients with MASLD, this marker did not improve the detection of MASLD in our study population, compared with either serum TG or HDL-C.

The role of PCSK9 in metabolic dysfunction-associated steatotic liver disease and its impact on bariatric surgery outcomes.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely tied to obesity. The degree ranges from steatosis (MASL) and steatohepatitis (MASH) to liver cirrhosis. PCSK9 controls cholesterol and lipid particle transport to the liver. PCSK9 might interfere with the pathophysiology of MASLD and bariatric surgery (BS) outcomes of patients with MASLD. OBJECTIVES: Evaluate the relationship between serum and hepatic PCSK9 levels with the degree of MASLD and the metabolic outcome of BS. SETTING: University Hospital, Spain. METHODS: A total of 110 patients with obesity undergoing BS were classified according to liver histology as controls, MAS, and MASH. PCSK9 levels in serum were measured before and 6 months after BS using enzyme-linked immunosorbent assay. PCSK9 protein and mRNA levels in liver tissue were analyzed by immunohistochemistry and reverse transcriptase-polymerase chain reaction, respectively. RESULTS: Hepatic PCSK9 protein levels were diminished in MASL and MASH compared with patients without MASLD and showed a strong negative association with MASLD severity scores. Liver PCSK9 mRNA was higher in MASH compared with controls and MASL and showed positive associations with MASLD severity scores. There were no differences in serum PCSK9 pre or postBS between the groups. Pre- and postsurgery serum PCSK9 positively correlated with cholesterol fold-changes and body mass index (BMI), cholesterol, and low-density lipoprotein -cholesterol fold-changes, respectively. PCSK9 fold-change positively correlated with BMI changes and was the sole variable explaining BMI fold changes in a regression model. CONCLUSIONS: PCSK9 mRNA and protein in the liver might be associated with the degree of MASLD. Serum PCSK9 may be associated with cholesterol and/or BMI fold changes. Serum changes of PCSK9 after BS could explain BMI loss outcome.

A novel model for predicting diabetes remission after bariatric surgery based on the measurement of C-peptide and creatinine in serum: A pilot study.

BACKGROUND AND AIMS: Bariatric surgery is effective for treating type 2 diabetes (T2D) in patients with obesity, although a significant proportion of these patients do not achieve diabetes remission after the surgery even after significant weight loss and metabolic improvement. C-peptide is a valuable marker of beta cell function and insulin secretion, but renal function must be considered when interpreting measurements in patients with T2D. The study aims to investigate the association of serum levels of C-peptide adjusted for creatinine with diabetes remission and glycemic target achievement after bariatric surgery in patients with obesity and T2D. METHODS AND RESULTS: Prospective data from a cohort of 84 patients with obesity and T2D submitted to Roux-en-Y gastric bypass (RYGB) were collected at baseline and at least a 6-month follow up. A multivariate binomial regression model showed that Ln(C-peptide/creatinine) and age were significantly associated with 6-month T2D remission. The area under the curve for the receiver operating characteristic analysis (AUROC) to predict remission was 0.87, and more accurate than the AUROC based on C-peptide levels alone (0.75). The same model was also able to predict achieving an HbA1c target of 7 % (53 mmol/mol) (AUROC 0.96). CONCLUSION: In conclusion, Ln(C-peptide/creatinine) ratio could be a useful tool in predicting T2D remission and target achievement after RYGB surgery, providing a more accurate reflection of beta cell function in bariatric patients.

Lipidomic Analysis Reveals Alterations in Hepatic FA Profile Associated With MASLD Stage in Patients With Obesity.

CONTEXT: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by the intracellular lipid accumulation in hepatocytes. Excess caloric intake and high-fat diets are considered to significantly contribute to MASLD development. OBJECTIVE: To evaluate the hepatic and serum fatty acid (FA) composition in patients with different stages of MASLD, and their relationship with FA dietary intake and MASLD-related risk factors. METHODS: This was a case-control study in patients with obesity undergoing bariatric surgery at a university hospital between January 2020 and December 2021. Participants were distributed in 3 groups: no MASLD (n = 26), steatotic liver disease (n = 33), and metabolic dysfunction-associated steatohepatitis (n = 32). Hepatic and serum FA levels were determined by gas chromatography-mass spectrometry. Nutritional status was evaluated using validated food frequency questionnaires. The hepatic expression of genes involved in FA metabolism was analyzed by reverse transcription quantitative polymerase chain reaction. RESULTS: The hepatic, but not serum, FA profiles were significantly altered in patients with MASLD compared with those without MASLD. No differences were observed in FA intake between the groups. Levels of C16:0, C18:1, and the C18:1/C18:0 ratio were higher, while C18:0 levels and C18:0/C16:0 ratio were lower in patients with MASLD, being significantly different between the 3 groups. Hepatic FA levels and ratios correlated with histopathological diagnosis and other MASLD-related parameters. The expression of genes involved in the FA metabolism was upregulated in patients with MASLD. CONCLUSION: Alterations in hepatic FA levels in MASLD patients were due to enhancement of de novo lipogenesis in the liver.

Plasma short-chain fatty acid changes after bariatric surgery in patients with severe obesity.

BACKGROUND: Obesity has reached epidemic dimensions in recent decades. Bariatric surgery (BS) is one of the most effective interventions for weight loss and metabolic improvement in patients with obesity. Short-chain fatty acids (SCFA) are gut microbiota-derived metabolites with a key role in body weight control and insulin sensitivity. Although BS is known to induce significant changes in the gut microbiota composition, its impact on the circulating levels of certain metabolites produced by the gut microbiota such as SCFA remains poorly understood. OBJECTIVE: To determine the impact of BS on the circulating SCFA levels in patients with severe obesity. SETTING: University hospital. METHODS: An observational, prospective study was performed on 51 patients undergoing Roux-en-Y gastric bypass. Plasma samples were collected at baseline (1 day before surgery) and at 6 and 12 months after BS. Plasma SCFA levels were determined by liquid chromatography-mass spectrometry. RESULTS: The results revealed significant changes in the circulating levels of SCFA after BS. A marked increase in propionate, butyrate, isobutyrate, and isovalerate levels and a decrease in acetate, valerate, hexanoate, and heptanoate levels were observed 12 months after BS. Furthermore, the changes in the levels of propionate, butyrate, and isobutyrate negatively correlated with changes in body mass index, while those of isobutyrate correlated negatively with changes in the homeostatic model assessment for insulin resistance index. CONCLUSION: These results suggest that propionate, butyrate, and isobutyrate levels could be related to weight loss and improved insulin sensitivity in patients with severe obesity after BS.

Management of older hospitalized patients with type 2 diabetes using linagliptin: Lina-Older study.

BACKGROUND: Older patients managed with intensive antidiabetic therapy are more likely to be harmed. Our study's primary endpoint was to analyze the safety and efficacy of linagliptin in combination with basal insulin versus basal-bolus insulin in patients with 75 years of age or older hospitalized in medicine and surgery departments in real-world clinical practice. METHODS: We retrospectively enrolled non-critically patients ≥75 years with type 2 diabetes admitted to medicine and non-cardiac surgery departments with admission glycated hemoglobin <8%, admission blood glucose <240 mg/dL, and without at-home injectable therapies managed with our hospital's antihyperglycemic protocol (basal-bolus or linagliptin-basal regimens) between January 2016 and December 2018. To match each patient who started on the basal-bolus regimen with a patient who started on the linagliptin-basal regimen, a propensity matching analysis was used. RESULTS: Postmatching, 198 patients were included in each group. There were no significant differences in mean daily blood glucose levels after admission (P=0.203); patients with mean blood glucose 100-140mg/dL (P=0.134), 140-180mg/dL (P=0.109), or >200mg/dL (P=0.299); and number and day of treatment failure (P=0.159 and P=0.175, respectively). The total insulin dose and the number of daily injections were significantly lower in the linagliptin-basal group (both, P<0.001). Patients on the basal-bolus insulin regimen had more total hypoglycemic events than patients on the linagliptin-basal insulin regimen (P<0.001). CONCLUSIONS: The linagliptin-basal insulin regimen was an effective alternative with fewer hypoglycemic events and daily insulin injections than intensive basal-bolus insulin in very old patients with type 2 diabetes with mild-to-moderate hyperglycemia treated at home without injectable therapies.

Crohn's Disease, Host-Microbiota Interactions, and Immunonutrition: Dietary Strategies Targeting Gut Microbiome as Novel Therapeutic Approaches.

Crohn's disease (CD) is a complex, disabling, idiopathic, progressive, and destructive disorder with an unknown etiology. The pathogenesis of CD is multifactorial and involves the interplay between host genetics, and environmental factors, resulting in an aberrant immune response leading to intestinal inflammation. Due to the high morbidity and long-term management of CD, the development of non-pharmacological approaches to mitigate the severity of CD has recently attracted great attention. The gut microbiota has been recognized as an important player in the development of CD, and general alterations in the gut microbiome have been established in these patients. Thus, the gut microbiome has emerged as a pre-eminent target for potential new treatments in CD. Epidemiological and interventional studies have demonstrated that diet could impact the gut microbiome in terms of composition and functionality. However, how specific dietary strategies could modulate the gut microbiota composition and how this would impact host-microbe interactions in CD are still unclear. In this review, we discuss the most recent knowledge on host-microbe interactions and their involvement in CD pathogenesis and severity, and we highlight the most up-to-date information on gut microbiota modulation through nutritional strategies, focusing on the role of the microbiota in gut inflammation and immunity.

Gut Microbiome Modification through Dietary Intervention in Patients with Colorectal Cancer: Protocol for a Prospective, Interventional, Controlled, Randomized Clinical Trial in Patients with Scheduled Surgical Intervention for CRC.

Colorectal cancer (CRC) is the third most common cancer and the second cause of cancer death worldwide. Several factors have been postulated to be involved in CRC pathophysiology, including heritable and environmental factors, which are the latest to be closely associated with nutritional habits, physical activity, obesity, and the gut microbiota. The latter may also play a key role in CRC prognosis and derived complications in patients undergoing surgery. This is a single-center, open, controlled, randomized clinical trial, in patients with scheduled surgical intervention for CRC. The primary objective is to assess whether a pre-surgical nutritional intervention, based on a high-fiber diet rich in polyunsaturated fatty acids (PUFAs), can reduce disturbances of the gut microbiota composition and, consequently, the rate of post-surgical complications in patients with CRC. Patients will be randomized in a 1:1 ratio after receiving a diagnosis of CRC. In the control arm, patients will receive standard nutritional recommendations, while patients in the intervention arm will be advised to follow a high-fiber diet rich in PUFAs before surgery. Participants will be followed up for one year to evaluate the overall rate of postsurgical complications, recurrences of CRC, response to adjuvant therapy, and overall/disease-free survival.

Variante anatómica sintomática de la duplicación de la vía biliar común tipo IV.

INTRODUCTION: Duplicity of the common bile duct is an unusual congenital disorder. CASE REPORT: A 80-year-old woman with duplication of the common bile duct with retrograde endoscopic cholangiopancreatography (ERCP) who did not resolve the symptoms. DISCUSSION: Our case is a variant of type IV to the classification of duplicity of the common bile duct. The magnetic resonance cholangiography and presurgical ERCP allows assessment of the bile ducts, their caliber, and assessment of abnormalities. The treatment before duplicity of the common bile duct will depend on the clinic and the type of opening of the accessory common bile duct. CONCLUSIONS: It is important to perform a pre-surgical study and during surgery with intrasurgical cholangiography.

INTRODUCCIÓN: La duplicidad del conducto biliar común es una alteración congénita insólita. CASO CLÍNICO: Mujer de 80 años con duplicación de la vía biliar común con colangiopancreatografías retrógradas endoscópicas (CPRE) que no solventan la clínica. DISCUSIÓN: Nuestro caso es una variante del tipo IV de la clasificación de duplicidad del conducto biliar común. La colangiopancreatografía por resonancia magnética y la CPRE prequirúrgica permiten valorar las vías biliares, su calibre y sus posibles anormalidades. El tratamiento dependerá de la clínica y del tipo de apertura del conducto biliar común accesorio. CONCLUSIONES: Es importante realizar un estudio prequirúrgico y durante la cirugía con colangiografía intraoperatoria.

Anatomy variant symptomatic of the duplication of the common bile duct type IV.

INTRODUCTION: Duplicity of the common bile duct (BCBD) is an unusual congenital disorder. CASE REPORT: A 80-year-old woman with duplication of the common bile duct with retrograde endoscopic cholangiopancreatography (ERCP) who did not resolve the symptoms. DISCUSSION: Our case is a variant of type IV to the classification of DCBC. The MR cholangiography and presurgical ERCP allows assessment of the bile ducts, their caliber, and assessment of abnormalities. The treatment before DCBC will depend on the clinic and the type of opening of the CBCA. CONCLUSIONS: It is important to perform a pre-surgical study and during surgery with CIO.

INTRODUCCIÓN: La duplicidad del conducto biliar común (DCBC) es una alteración congénita insólita. CASO CLÍNICO: Mujer de 80 años con duplicación de la vía biliar común con colangiopancreatografía retrógrada endoscópica (CPRE) que no dilucida la clínica. DISCUSIÓN: Este caso es una variante del tipo IV de la clasificación de DCBC. La colangiorresonancia y la CPRE prequirúrgica permiten valorar las vías biliares, su calibre y las anormalidades. El tratamiento depende de la clínica y el tipo de apertura del conducto biliar común accesorio. CONCLUSIONES: Es importante realizar estudio prequirúrgico y durante la operación con colangiografía intraoperatoria.

Fish Oil Enriched Intravenous Lipid Emulsions Reduce Triglyceride Levels in Non-Critically Ill Patients with TPN and Type 2 Diabetes. A Post-Hoc Analysis of the INSUPAR Study.

There are no studies that have specifically assessed the role of intravenous lipid emulsions (ILE) enriched with fish oil in people with diabetes receiving total parenteral nutrition (TPN). The objective of this study was to assess the metabolic control (glycemic and lipid) and in-hospital complications that occurred in non-critically ill inpatients with TPN and type 2 diabetes with regard to the use of fish oil emulsions compared with other ILEs. We performed a post-hoc analysis of the Insulin in Parenteral Nutrition (INSUPAR) trial that included patients who started with TPN for any cause and that would predictably continue with TPN for at least five days. The study included 161 patients who started with TPN for any cause. There were 80 patients (49.7%) on fish oil enriched ILEs and 81 patients (50.3%) on other ILEs. We found significant decreases in triglyceride levels in the fish oil group compared to the other patients. We did not find any differences in glucose metabolic control: mean capillary glucose, glycemic variability, and insulin dose, except in the number of mild hypoglycemic events that was significantly higher in the fish oil group. We did not observe any differences in other metabolic, liver or infectious complications, in-hospital length of stay or mortality.

Transcriptional Analysis of FOXO1, C/EBP-α and PPAR-γ2 Genes and Their Association with Obesity-Related Insulin Resistance.

BACKGROUND: Obesity is associated with several comorbid disorders, ranging from cardiovascular diseases to insulin resistance. In this context, visceral adipose tissue (VAT) seems to have a close connection with insulin resistance. In our study, we hypothesized that the expression profile of key adipogenic genes, such as proliferator-activated receptor γ type 2 (PPAR-γ2), CCAAT/enhancer-binding protein type α (C/EBP-α), and forkhead box protein class O type 1 (FOXO1) in VAT should shed light on their association with obesity-related insulin resistance. METHODS: To test this idea, we studied the expression profile of C/EBP-α, FOXO1 and PPAR-γ2 in VAT from non-obese individuals, and low insulin (LIR-MO) and high insulin morbidly obese (HIR-MO) subjects, through a combination of RT-qPCR, co-immunoprecipitation, ELISA, Western blot analysis and EMSA assays. RESULTS: Our results show that C/EBP-α and PPAR-γ2 were down-expressed in HIR-MO individuals, while FOXO1 was overexpressed. In addition, the PPAR-γ2-RXR-α heterodimer showed weak activity and bound weakly to the putative IGFBP-2-PPRE promoter sequence in VAT from HIR-MO subjects when compared with LIR-MO individuals. CONCLUSIONS: These results show that PPAR-γ2, C/EBP-α, FOXO1 and IGFBP-2 have a close relationship with insulin resistance in VAT of morbidly obese individuals.

Screening Versus Brief Domain-specific Tests to Assess Long-term Postoperative Cognitive Dysfunction After Concomitant Aortic Valve Replacement and Coronary Artery Bypass Grafting.

BACKGROUND: Although postoperative cognitive dysfunction is a relevant complication after surgery, assessment for the condition is not routine in clinical practice. OBJECTIVE: The aim of this study was to compare the use of screening versus brief domain-specific cognitive tests in assessing long-term cognitive dysfunction after concomitant aortic valve replacement and coronary artery bypass grafting. METHODS: In this observational prospective study, we evaluated 70 patients preoperatively and after 1, 6, and 12 months using 2 screening tests (Mini-Mental State Examination and Clock Drawing Test) and 2 brief domain-specific cognitive tests (Trail Making Test to evaluate attention and executive function, and Semantic and Phonological Tests to evaluate verbal fluency). RESULTS: The brief domain-specific cognitive tests detected significant postoperative worsening in performances (up to 19% on the Trail Making Test and 15.4% on verbal fluency tests at 6 months). Postoperative mild attention/executive dysfunction or inferior normal performance was detected with the maximums being seen at 6 months (44.6%, P < .001). Performances on screening tests did not significantly change during the study period. CONCLUSIONS: A brief domain-specific cognitive evaluation could be routinely implemented in perioperative care practice to detect postoperative cognitive dysfunction.

Oxidative stress in testes of rats exposed to n-butylparaben.

This study was aimed at determining if oxidative stress imbalance in testes of rats occurs after n-butylparaben (n-ButP) exposure. Young male Sprague-Dawley rats were subcutaneously treated with n-ButP during one spermatogenic cycle (57 days) at 0 (control-oil), 150, 300 and 600 mg/kg/d with peanut oil as vehicle. A non-vehicle control group was also included. Antioxidant enzyme activities (superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase) and levels of reduced and oxidized glutathione were measured in testes. Lipid peroxidation and H2O2 concentrations were also assessed. Results showed an increase of oxidative stress in oil-treated groups, excepting 600 mg/kg/d, suggesting oxidative stress due to peanut oil. A possible antioxidant effect due to n-ButP and its metabolites was suggested at 600 mg/kg/d, the only group not showing oxidative stress. An increase of calcium concentration in testes was also observed. On the other hand, a physiologically-based pharmacokinetic (PBPK) model was developed and the concentrations of n-ButP and its metabolites were simulated in plasma and testes. The peak concentration (Cmax) in testes was found slightly higher than that in plasma. The current results indicate that peanut oil can cause oxidative stress while high doses of n-ButP can act as antioxidant agent in testes.

Glycaemic efficacy and safety of linagliptin for the management of non-cardiac surgery patients with type 2 diabetes in a real-world setting: Lina-Surg study.

Introduction: The use of dipeptidyl peptidase-4 inhibitors in hospitalized patients is an area of active research. We aimed to compare the efficacy and the safety of the basal-bolus insulin regimen versus linagliptin-basal insulin in non-critically ill non-cardiac surgery patients in a real-world setting. Methods: We enrolled patients with type 2 diabetes hospitalized in non-cardiac surgery departments with admission glycated haemoglobin level < 8%, admission blood glucose concentration < 240 mg/dL, and no at-home injectable treatments who were treated with basal-bolus (n = 347) or linagliptin-basal (n = 190) regimens between January 2016 and December 2017. To match patients on the two regimens, a propensity matching analysis was performed. Results: After matching, 120 patients were included in each group. No differences were noted in mean blood glucose concentration after admission (p = .162), number of patients with a mean blood glucose 100-140 mg/dL (p = .163) and > 200 mg/dL (p = .199), and treatment failures (p = .395). Total daily insulin and number of daily insulin injections were lower in the linagliptin-basal group (both p < .001). Patients on linagliptin-basal insulin had fewer hypoglycaemic events (blood glucose < 70 mg/dL) (p < .001). Conclusion: For type 2 diabetes surgery patients with mild to moderate hyperglycaemia without pre-hospitalization injectable therapies, linagliptin-basal insulin was an effective, safe alternative with fewer hypoglycaemic events in real-world practice. Key messages Treatment with basal-bolus insulin regimens is the standard of care for non-critically ill hospitalized patients with type 2 diabetes. A differentiated treatment protocol that takes into account glycaemic control and clinical factors should be implemented in the hospital setting. Linagliptin-basal insulin is an effective, safe alternative with fewer hypoglycaemic events during the hospitalization of non-critically ill non-cardiac surgery patients with T2D in real-world practice.

Overexpression of scavenger receptor and infiltration of macrophage in epicardial adipose tissue of patients with ischemic heart disease and diabetes.

BACKGROUND: Oxidized low-density lipoproteins and scavenger receptors (SRs) play an important role in the formation and development of atherosclerotic plaques. However, little is known about their presence in epicardial adipose tissue (EAT). The objective of the study was to evaluate the mRNA expression of different SRs in EAT of patients with ischemic heart disease (IHD), stratifying by diabetes status and its association with clinical and biochemical variables. METHODS: We analyzed the mRNA expression of SRs (LOX-1, MSR1, CXCL16, CD36 and CL-P1) and macrophage markers (CD68, CD11c and CD206) in EAT from 45 patients with IHD (23 with type 2 diabetes mellitus (T2DM) and 22 without T2DM) and 23 controls without IHD or T2DM. RESULTS: LOX-1, CL-P1, CD68 and CD11c mRNA expression were significantly higher in diabetic patients with IHD when compared with those without T2DM and control patients. MSR1, CXCL16, CD36 and CD206 showed no significant differences. In IHD patients, LOX-1 (OR 2.9; 95% CI 1.6-6.7; P = 0.019) and CD68 mRNA expression (OR 1.7; 95% CI 0.98-4.5; P = 0.049) were identified as independent risk factors associated with T2DM. Glucose and glycated hemoglobin were also shown to be risk factors. CONCLUSIONS: SRs mRNA expression is found in EAT. LOX-1 and CD68 and were higher in IHD patients with T2DM and were identified as a cardiovascular risk factor of T2DM. This study suggests the importance of EAT in coronary atherosclerosis among patients with T2DM.

Role of Melatonin in Aluminum-Related Neurodegenerative Disorders: a Review.

Aluminum (Al), a potentially neurotoxic element, provokes various adverse effects on human health such as dialysis dementia, osteomalacia, and microcytic anemia. It has been also associated with serious neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis, and Parkinsonism dementia of Guam. The "aluminum hypothesis" of AD assumes that the metal complexes can potentiate the rate of aggregation of amyloid-ß (Aß), enhancing the toxicity of this peptide, and being able of contributing to the pathogenesis of AD. It has been supported by a number of analytical, epidemiological, and neurotoxicological studies. On the other hand, melatonin (Mel) is a potent direct free radical scavenger and indirect antioxidant, which acts increasing the activity of important related antioxidant enzymes, and preventing oxidative stress and cell death of neurons exposed to Aß-induced neurotoxicity. Therefore, Mel might be useful in the treatment of AD by reducing the Aß generation and by inhibiting mitochondrial cell death pathways. The present review on the role of Mel in Al-related neurodegenerative disorders concludes that the protective effects of this hormone, together with its low toxicity, support the administration of Mel as a potential supplement in the treatment of neurological disorders, in which oxidative stress is involved.

Interactions between callose and cellulose revealed through the analysis of biopolymer mixtures.

The properties of (1,3)-ß-glucans (i.e., callose) remain largely unknown despite their importance in plant development and defence. Here we use mixtures of (1,3)-ß-glucan and cellulose, in ionic liquid solution and hydrogels, as proxies to understand the physico-mechanical properties of callose. We show that after callose addition the stiffness of cellulose hydrogels is reduced at a greater extent than predicted from the ideal mixing rule (i.e., the weighted average of the individual components' properties). In contrast, yield behaviour after the elastic limit is more ductile in cellulose-callose hydrogels compared with sudden failure in 100% cellulose hydrogels. The viscoelastic behaviour and the diffusion of the ions in mixed ionic liquid solutions strongly indicate interactions between the polymers. Fourier-transform infrared analysis suggests that these interactions impact cellulose organisation in hydrogels and cell walls. We conclude that polymer interactions alter the properties of callose-cellulose mixtures beyond what it is expected by ideal mixing.

Oral exposure to silver nanoparticles increases oxidative stress markers in the liver of male rats and deregulates the insulin signalling pathway and p53 and cleaved caspase 3 protein expression.

The present study was aimed at assessing the impact of AgNPs on the liver of male rats orally exposed to 0, 50, 100 and 200 mg/kg/day of polyvinyl pyrrolidone coated AgNPs (PVP-AgNPs) for 90 days. The induction of apoptotic cell death -by measuring the protein levels of the active form of caspase 3- and the levels of the microtubule-associated protein 1A/1B-light chain (LC3) protein were measured as a marker of the induction of autophagy. PVP-AgNPs caused an increase of the activity of superoxide dismutase (SOD) and catalase (CAT) in the liver of male rats. However, the activity decreased after exposure to high amounts of PVP-AgNPs. Increased protein levels of IRS-1, AKT, GSK3ß and mTOR proteins were observed in a dose-dependent manner. However, these proteins showed a decrease at 200 mg/kg/day. The same pattern was observed for the p53, p21 and cleaved caspase 3 protein levels. The current results suggest that the increase of ROS production by PVP-AgNPs stimulated SOD and CAT activity, as well as IRS-1, AKT, mTOR, p53, p21 and caspase 3 as protective mechanisms of cell survival and preserve DNA fidelity. However, cellular damage by excessive ROS production might induce the depletion of these survival mechanisms at 200 mg/kg/day.