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Fetal programming occurs during the gestational age when exposure to environmental stimuli can cause long-term changes in the fetus, predisposing it to develop chronic non-communicable diseases (CNCD) in adulthood. Herein, we summarized the role of low-calorie or high-fat diets during pregnancy as fetal programming agents that induce intrauterine growth restriction (IUGR), amplified de novo lipogenesis, and increased amino acid transport to the placenta, which favor the CNCD onset in the offspring. We also outlined how maternal obesity and gestational diabetes act as fetal programming stimuli by reducing iron absorption and oxygen transport to the fetus, stimulating inflammatory pathways that boost neurological disorders and CNCD in the progeny. Moreover, we reviewed the mechanisms through which fetal hypoxia elevates the offspring’s risk of developing hypertension and chronic kidney disease in adult life by unbalancing the renin-angiotensin system and promoting kidney cell apoptosis. Finally, we examined how inadequate vitamin B12 and folic acid consumption during pregnancy programs the fetus to greater adiposity, insulin resistance, and glucose intolerance in adulthood. A better understanding of the fetal programming mechanisms may help us reduce the onset of insulin resistance, glucose intolerance, dyslipidemia, obesity, hypertension, diabetes mellitus, and other CNCD in the offspring during adulthood.

The outbreak of coronavirus disease 2019 (COVID-19) is caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). COVID-19 and type 2 diabetes (T2D) have now merged into an ongoing global syndemic that is threatening the lives of millions of people around the globe. For this reason, there is a deep need to understand the immunometabolic bases of the main etiological factors of T2D that affect the severity of COVID-19. Here, we discuss how hyperglycemia contributes to the cytokine storm commonly associated with COVID-19 by stimulating monocytes and macrophages to produce interleukin IL-1β, IL-6, and TNF-α in the airway epithelium. The main mechanisms through which hyperglycemia promotes reactive oxygen species release, inhibition of T cell activation, and neutrophil extracellular traps in the lungs of patients with severe SARS-CoV-2 infection are also studied. We further examine the molecular mechanisms by which proinflammatory cytokines induce insulin resistance, and their deleterious effects on pancreatic β-cell exhaustion in T2D patients critically ill with COVID-19. We address the effect of excess glucose on advanced glycation end product (AGE) formation and the role of AGEs in perpetuating pneumonia and acute respiratory distress syndrome. Finally, we discuss the contribution of preexisting endothelial dysfunction secondary to diabetes in the development of neutrophil trafficking, vascular leaking, and thrombotic events in patients with severe SARS-CoV-2 infection. As we outline here, T2D acts in synergy with SARS-CoV-2 infection to increase the progression, severity, and mortality of COVID-19. We think a better understanding of the T2D-related immunometabolic factors that contribute to exacerbate the severity of COVID-19 will improve our ability to identify patients with high mortality risk and prevent adverse outcomes.

Interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) are associated with body weight alterations in children, adolescents, and adults. However, little is known regarding the role of IL-10 and IFN-gamma in birth weight of neonates. One hundred eighty-two infants were enrolled and divided in groups of normal birth weight (95th percentile) or increased birth weight (95th percentile) for gestational age. IL-10 and IFN-gamma levels were measured in umbilical cord tissue and blood of newborns by quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). The average value of birth weight in infants below and above the 95th percentile was 3.03±0.39 and 3.58±0.37 kg, respectively, and was independent of the mother's pre-gestational body mass index. The Student t test revealed that neonates with birth weights95th percentile show a significant 30% decrease in cord blood values of IL-10 as compared to infants with birth weights95th percentile (P0.0001), with no significant changes in IFN-gamma levels (P=0.1661). Cord blood IL-10 was not of maternal origin but produced by umbilical cord tissue that showed less IL-10 expression in neonates with birth weights95th percentile than in infants with birth weights95th percentile (P=0.0252). Cord blood levels of IL-10 exhibited significant inverse correlations with birth weight (r = - 0.658, P=0.002) and INF-gamma (r = - 0.502, P=0.005).Conclusion: In conclusion, this work demonstrates for the first time that cord blood IL-10 decreases as birth weight increases in infants born at term and might help to improve early recognition of newborns at higher risk of developing obesity in childhood or adulthood. What is Known: • Reduction in interleukin-10 levels has been associated with obesity in adolescents and adults but not newborns. • The number of neonates with excess birth weight has alarmingly increased in the last 30 years. What is New: • We demonstrate that umbilical cord blood levels of interleukin-10 clearly decrease as birth weight increases. • Interleukin-10 and interferon-gamma integrate a cytokine network that might play a role in obesity in infants.

The differential contribution of monocyte subsets expressing the C-C chemokine receptor 2 (CCR2) to subclinical atherosclerosis in girls and boys is unclear. In this pilot study, we compared classical, intermediate, and nonclassical monocyte subsets expressing CCR2 in 33 obese children of both sexes aged 8 to 16 divided by carotid intima-media thickness (IMT), considering values above the 75th percentile (p75) as abnormally high IMT. Obesity was defined as body mass index above the 95th percentile according to age and sex. Flow cytometry analyses revealed that boys but not girls with IMT ≥ p75 displayed increased CCR2

The contribution of the cellular immune response to the severity of coronavirus disease 2019 (COVID-19) is still uncertain because most evidence comes from patients receiving multiple drugs able to change immune function. Herein, we conducted a prospective cohort study and obtained blood samples from 128 unvaccinated healthy volunteers to examine the in vitro response pattern of CD4+ and CD8+ T cells and monocyte subsets to polyclonal stimuli, including anti-CD3, anti-CD28, poly I:C, severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) recombinant spike S1 protein, and lipopolysaccharide. Then, we started a six-month follow-up and registered 12 participants who got SARS-CoV-2 infection, from whom we retrospectively analyzed the basal immune response pattern of T cells and monocytes. Of the 12 participants infected, six participants developed mild COVID-19 with self-limiting symptoms such as fever, headache, and anosmia. Conversely, six other participants developed severe COVID-19 with pneumonia, respiratory distress, and hypoxia. Two severe COVID-19 cases required invasive mechanical ventilation. There were no differences between mild and severe cases for demographic, clinical, and biochemical baseline characteristics. In response to polyclonal stimuli, basal production of interleukin-2 (IL-2) and interferon (IFN-) gamma significantly decreased, and the programmed cell death protein 1 (PD-1) increased in CD4+ and CD8+ T cells from participants who posteriorly developed severe COVID-19 compared to mild cases. Likewise, CD14++CD16- classical and CD14+CD16+ non-classical monocytes lost their ability to produce IFN-alpha in response to polyclonal stimuli in participants who developed severe COVID-19 compared to mild cases. Of note, neither the total immunoglobulin G serum titers against the virus nor their neutralizing ability differed between mild and severe cases after a month of clinical recovery. In conclusion, using in vitro polyclonal stimuli, we found a basal immune response pattern associated with a predisposition to developing severe COVID-19, where high PD-1 expression and low IL-2 and IFN-gamma production in CD4+ and CD8+ T cells, and poor IFN-alpha expression in classical and non-classical monocytes are linked to disease worsening. Since antibody titers did not differ between mild and severe cases, these findings suggest cellular immunity may play a more crucial role than humoral immunity in preventing COVID-19 progression.

SARS-CoV-2 causes COVID-19, which has claimed millions of lives. This virus can infect various cells and tissues, including the brain, for which numerous neurological symptoms have been reported, ranging from mild and non-life-threatening (e.g., headaches, anosmia, dysgeusia, and disorientation) to severe and life-threatening symptoms (e.g., meningitis, ischemic stroke, and cerebral thrombosis). The cellular receptor for SARS-CoV-2 is angiotensin-converting enzyme 2 (ACE2), an enzyme that belongs to the renin-angiotensin system (RAS). RAS is an endocrine system that has been classically associated with regulating blood pressure and fluid and electrolyte balance; however, it is also involved in promoting inflammation, proliferation, fibrogenesis, and lipogenesis. Two pathways constitute the RAS with counter-balancing effects, which is the key to its regulation. The first axis (classical) is composed of angiotensin-converting enzyme (ACE), angiotensin (Ang) II, and angiotensin type 1 receptor (AT1R) as the main effector, which -when activated- increases the production of aldosterone and antidiuretic hormone, sympathetic nervous system tone, blood pressure, vasoconstriction, fibrosis, inflammation, and reactive oxygen species (ROS) production. Both systemic and local classical RAS’ within the brain are associated with cognitive impairment, cell death, and inflammation. The second axis (non-classical or alternative) includes ACE2, which converts Ang II to Ang-(1–7), a peptide molecule that activates Mas receptor (MasR) in charge of opposing Ang II/AT1R actions. Thus, the alternative RAS axis enhances cognition, synaptic remodeling, cell survival, cell signal transmission, and antioxidant/anti-inflammatory mechanisms in the brain. In a physiological state, both RAS axes remain balanced. However, some factors can dysregulate systemic and local RAS arms. The binding of SARS-CoV-2 to ACE2 causes the internalization and degradation of this enzyme, reducing its activity, and disrupting the balance of systemic and local RAS, which partially explain the appearance of some of the neurological symptoms associated with COVID-19. Therefore, this review aims to analyze the role of RAS in the development of the neurological effects due to SARS-CoV-2 infection. Moreover, we will discuss the RAS-molecular targets that could be used for therapeutic purposes to treat the short and long-term neurological COVID-19-related sequelae.

There is scant information regarding the role of interleukin (IL)-6 in obesity-related metabolic dysfunction in humans. Thus, we studied the serum levels of IL-6 in normal weight, overweight, and obese subjects, and examined associations of IL-6 with hyperglycemia, insulin resistance, dyslipidemia, and systemic inflammation. One hundred three women and men were included in the study. Anthropometric parameters, blood glucose, insulin, total cholesterol, and triglycerides were measured. Serum levels of tumor necrosis factor-alpha (TNF-alpha), IL-10, and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). One-way analysis of variance (ANOVA) showed a 2.5-fold significant decrease in serum IL-6 in overweight and obese individuals when compared with normal weight controls. Serum IL-6 exhibited significant inverse correlations with body mass index (

Health care workers (HCW) are at high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The incidence of SARS-CoV-2 infection in HCW has been examined in cross-sectional studies by quantitative polymerase chain reaction (qPCR) tests, which may lead to underestimating exact incidence rates. We thus investigated the incidence of SARS-CoV-2 infection in a group of HCW at a dedicated coronavirus disease 2019 (COVID-19) hospital in a six-month follow-up period. We conducted a prospective cohort study on 109 participants of both sexes working in areas of high, moderate, and low SARS-CoV-2 exposure. qPCR tests in nasopharyngeal swabs and anti-SARS-CoV-2 IgG serum antibodies were assessed at the beginning and six months later. Demographic, clinical, and laboratory parameters were analyzed according to IgG seropositivity by paired Student’s T-test or the chi-square test. The incidence rate of SARS-CoV-2 infection was considerably high in our cohort of HCW (58%), among whom 67% were asymptomatic carriers. No baseline risk factors contributed to the infection rate, including the workplace. It is still necessary to increase hospital safety procedures to prevent virus transmissibility from HCW to relatives and non-COVID-19 patients during the upcoming waves of contagion.

Background. Human milk is essential for establishing the newborn’s gut microbiota, which can have an impact on future health. Several studies indicate that Non-nutritive Sweeteners (NNS) can modify the intestinal microbiota, promoting metabolic dysfunction in humans and rodents; however, the influence of NNS on human milk microbiota is unknown. This study aimed to assess changes in the relative abundance of several of bacterial groups in colostrum of women who consumed NNS during pregnancy. Methods. This cross-sectional, pilot study included 39 women that gave birth to a live, healthy newborn in the General Hospital of Mexico. We assessed mothers’ diet and NNS consumption by validated questionnaires and the relative abundance of Bifidobacteriaceae, Lactobacillaceae, Lachnospiraceae, Roseburia, Eubacteriales, and Bacteroidales in colostrum samples by real-time PCR.Results. Twenty-six women (66%) showed a low NNS consumption (Lactobacillaceae relative abundance significantly decreased in the high NNS consumption group compared to the low NNS group (12.36±11.29 vs. 4.41±2.84, respectively; P<.001). NNS consumption associated with lower gestational age determined by the Capurro method or Ultrasound/Last Menstrual Period (r=-0.320, P= .025; and r=-0.355, P= .018, respectively).Conclusion. NNS consumption during pregnancy is associated with decreased Lactobacillaceae abundance in colostrum and lower gestational age. The effects of NNS consumption during pregnancy on breast milk microbiota and gestational age should be further investigated.Study registration: This study was registered in ClinicalTrials, number NCT03912038.

Background: A diet containing non-caloric sweeteners (NCS) could reduce calorie intake; conversely, some animal studies suggest that NCS consumption may increase functional gastrointestinal disorder symptoms (FGDs). This study aimed to compare the effect of consuming a diet containing NCS (c-NCS) versus a non-caloric sweetener-free diet (NCS-f) on FGDs. Methods: We conducted a randomized, controlled, parallel-group study using two different diets for five weeks: the c-NCS diet contained 50–100 mg/day NCS, whereas the NCS-f diet had less than 10 mg/day NCS. At the beginning of the study (PreTx) and at the end (PostTx), we assessed FGDs, dietary intake, and NCS consumption. Results: The percentage of participants with diarrhea (PreTx = 19% vs. PstTx = 56%; p = 0.02), post-prandial discomfort (PreTx = 9% vs. PstTx = 39%; p = 0.02), constipation (PreTx = 30% vs. PostTx = 56%; p < 0.01), and burning (PreTx = 13% vs. PostTx = 33%; p < 0.01) increased in the c-NCS diet group. Conversely, abdominal pain (PreTx = 15% vs. PostTx = 3%; p = 0.04), post-prandial discomfort (PreTx = 26% vs. PostTx = 6%; p = 0.02), burning (PreTx = 15% vs. PostTx = 0%; p = 0.02), early satiety (PreTx = 18% vs. PostTx = 3%; p < 0.01), and epigastric pain (PreTx = 38% vs. PostTx = 3%; p < 0.01) decreased in the NCS-f diet group. Conclusion: A c-NCS diet is associated with increased FGDs, including diarrhea, post-prandial discomfort, constipation, and burning or retrosternal pain. The NCS-f diet also decreased FGDs, as well as abdominal pain, post-prandial discomfort, burning or retrosternal pain, early satiety, and epigastric pain.

Sucralose consumption alters microbiome and carbohydrate metabolism in mouse models. However, there are no conclusive studies in humans. Our goals were to examine the effect of sucralose consumption on the intestinal abundance of bacterial species belonging to Actinobacteria, Bacteroidetes, and Firmicutes and explore potential associations between microbiome profiles and glucose and insulin blood levels in healthy young adults. In this open-label clinical trial, volunteers randomly drank water, as a control (n = 20), or 48 mg sucralose (n = 20), every day for ten weeks. At the beginning and the end of the study, participants were subjected to an oral glucose tolerance test (OGTT) to measure serum glucose and insulin every 15 min for 3 h and provided fecal samples to assess gut microbiota using a quantitative polymerase chain reaction. Sucralose intake altered the abundance of Firmicutes without affecting Actinobacteria or Bacteroidetes. Two-way ANOVA revealed that volunteers drinking sucralose for ten weeks showed a 3-fold increase in Blautia coccoides and a 0.66-fold decrease in Lactobacillus acidophilus compared to the controls. Sucralose consumption increased serum insulin and the area under the glucose curve compared to water. Long-term sucralose ingestion induces gut dysbiosis associated with altered insulin and glucose levels during an OGTT.

Laboratory parameters display limited accuracy in predicting mortality in coronavirus disease 2019 (COVID-19) patients, as with serum albumin. Emerging evidence suggests that cytokine serum values may enhance the predictive capacity of albumin, especially interleukin (IL)-15. We thus investigated whether the use of the IL-15-to-albumin ratio enables improving mortality prediction at hospital admission in a large group of COVID-19 patients. In this prospective cross-sectional study, we enrolled and followed up three hundred and seventy-eight patients with a COVID-19 diagnosis until hospital discharge or death. Two hundred and fifty-five patients survived, whereas one hundred and twenty-three died. Student’s T-test revealed that non-survivors had a significant two-fold increase in the IL-15-to-albumin ratio compared to survivors (167.3 ± 63.8 versus 74.2 ± 28.5), a difference that was more evident than that found for IL-15 or albumin separately. Likewise, mortality prediction considerably improved when using the IL-15-to-albumin ratio with a cut-off point > 105.4, exhibiting an area under the receiver operating characteristic curve of 0.841 (95% Confidence Interval, 0.725–0.922, p < 0.001). As we outlined here, this is the first study showing that combining IL-15 serum values with albumin improves mortality prediction in COVID-19 patients.

Context: CD4+ T lymphocytes are able to differentiate into distinct subtypes according to several immunological scenarios, including T helper (Th)1, Th2, Th17 and regulatory T (Treg) cells. CD4+ T cells are phenotypically flexible and have specific ion channels, such as the nicotinic acetylcholine receptors (nAChR) that could be modulated by peptides produced by marine snails, known as conotoxins. Their effect on T lymphocytes has not been explored and emerging evidence suggests that these peptides may have immunomodulatory activities. Objective: This study investigated the effect of two Californiconus californicus-derived synthetic conotoxins on the proliferation and differentiation of T lymphocyte subpopulations Th1, Th2, Th17 and Treg. Methods: Cells from lymph nodes of BALB/c mice were cultured in the presence of conotoxins cal14.1b and cal14.2c (5.5 μM), during 96 h. Cell proliferation and intracellular cytokine production (IFN-γ, IL-4, IL-17 and IL-10) were analyzed by flow cytometry. Results and Discussion: cal14.1b and cal14.2c increased intracellular IL-10 production in Treg (CD3+CD4+Foxp3+) cells and decreased intracellular IL-17 production (CD3+CD4+) after 72 h of culture. Conotoxins did not show any effect on T cell proliferation nor Th1/Th2 balance. Conclusion: These results suggest that synthetic conotoxins exert immunomodulatory activity, especially by regulating specific functions on T lymphocytes.

BackgroundA diet containing Non-Caloric Sweeteners (NCS) is used to reduce calorie intake and blood sugar peaks in overweight and obese subjects. Nevertheless, some animal studies suggest that NCS consumption may increase Functional Gastrointestinal Disorder symptoms (FGDs); however, there are scant clinical trials in humans. The aim of the study was to compare the effect of consuming a diet containing NCS (c-NCS) versus a Non-Caloric Sweetener-free diet (NCS-f) on FGDs in adult volunteers.MethodsThis was a randomized, controlled, parallel-group study using two different diets for five weeks: diet c-NCS contained 50-100 mg/day NCS (80% sucralose and 20% aspartame, acesulfame K, and saccharin); NCS-f diet contained less than 10 mg/day NCS. FGDs were recorded according to the Rome III criteria, gastrointestinal symptom questionnaire, Bristol scale, food frequency questionnaire, and consumption questionnaire at the beginning (PreTx) and at the end (PostTx) of the study by a gastroenterologist and a nutritionist. This study conducted according to the CONSORT guidelines and it was registered at clinicaltrials.gov (identifier code: NCT04129762).ResultsParticipants were more often women than men in both groups (59% and 62%), with a median age of 22 years. FGDs were similar in both groups at the beginning of the study (PreTx) but significantly increased in the diet c-NCS group after five weeks (PostTx). The percentage of participants with diarrhea (PreTx=19% versus PstTx=56%; p=0.02), post-prandial discomfort (PreTx=9% versus PstTx=39%; p=0.02), constipation (PreTx=30% versus PostTx=56%; pConclusion This study shows that diet c-NCS associates with increased FGDs including diarrhea, post-prandial discomfort, constipation, and burning or retrosternal pain. Interestingly, NCS-f diet concurs with decreased FGDs such as abdominal pain, post-prandial discomfort, burning or retrosternal pain, early satiety, and epigastric pain. A NCS-f diet could be a complementary strategy to alleviate FGDs. Trial registration: The ethics committee of the hospital approved this study with the registration number DI/19/301/03/020. This trial was registered at clinicaltrials.gov (identifier code: NCT04129762).

Background Non-nutritive sweeteners (NNS) are widely consumed by humans due to their apparent innocuity, especially sucralose. However, several studies link sucralose consumption to weight gain and metabolic derangements, although data are still contradictory. Objective To determine the effect of acute and chronic consumption of sucralose on insulin and glucose profiles in young healthy adults. Material and methods This was a randomized, parallel, double-blind, placebo-controlled trial conducted in healthy young adults from 18 to 35 years old, without insulin resistance. A hundred thirty seven participants were randomized into three groups: a) volunteers receiving 48 mg sucralose, b) volunteers receiving 96 mg sucralose, and c) controls receiving water as placebo. All participants underwent a 3-h oral glucose tolerance test (OGTT) preceded by consuming sucralose or placebo 15 min before glucose load, at two time points: week zero (Wk0) and week ten (Wk10). Serum insulin and glucose were measured every 15 min during both OGTTs. Results Compared to Wk0, consumption of sucralose for 10 weeks provoked 1) increased insulin concentrations at 0 min (7.5 ± 3.4 vs 8.8 ± 4.1 μIU/mL; p = 0.01), 30 min (91.3 ± 56.2 vs 110.1 ± 49.4 μIU/mL; p = 0.05), 105 min (47.7 ± 24.4 vs 64.3 ± 48.2 μIU/mL; p = 0.04) and 120 min (44.8 ± 22.1 vs 63.1 ± 47.8 μIU/mL; p = 0.01) in the 48 mg sucralose group; 2) increased blood glucose at − 15 min (87.9 ± 4.6 vs 91.4 ± 5.4 mg/dL; p = 0.003), 0 min (88.7 ± 4 vs 91.3 ± 6 mg/dL; p = 0.04) and 120 min (95.2 ± 23.7 vs 106.9 ± 19.5 mg/dL; p = 0.009) in the 48 mg sucralose group; 3) increased area under the curve (AUC) of insulin in both 48 and 96 mg sucralose groups (9262 vs 11,398; p = 0.02 and 6962 vs 8394; p = 0.12, respectively); and 4) reduced Matsuda index in the 48 mg sucralose group (6.04 ± 3.19 vs 4.86 ± 2.13; p = 0.01). Conclusions These data show that chronic consumption of sucralose can affect insulin and glucose responses in non-insulin resistant healthy young adults with normal body mass index (between 18.5 and 24.9 kg/m2), however, the effects are not consistent with dose; further research is required. Clinical trial registry NCT03703141.

The neuroimmunoregulation of inflammation has been well characterized. Entamoeba histolytica provokes an inflammatory response in the host in which macrophages and neutrophils are the first line of defense. The aim of this study was to analyze the effect of the 220 kDa lectin of Entamoeba histolytica on stimulation of human macrophages and neutrophils, especially the secretion of cytokines and the relation of these to neurotransmitters. Human cells were interacted with L220, epinephrine, nicotine, esmolol and vecuronium bromide. The concentrations of IL-1β, IFN-γ, TNF-α and IL-10 were determined by ELISA at, 4 h of interaction. L220 has a cytokine stimulating function of macrophages and neutrophils for secretion of IL-1β, and IL-10 only by macrophages, which was modulated by the effect of vecuronium on cholinergic receptors in this immune cells.

During the last years, fluorescence spectroscopy has been used as a potential tool for the evaluation and characterization of tissues with different disease conditions due to its low cost, high sensitivity, and minimally or noninvasive character.In this study, fluorescence spectroscopy was used to study 19 paraffin blocks containing human liver tissue from biopsies.All samples were previously analyzed by two senior pathologists in a single-blind trial. After their evaluation, four liver samples were classified as nonfibrosis (F0), four as initial fibrosis (F1-F2), four as advanced fibrosis (F3), and six as cirrhosis (F4). The fluorescence was induced at different wavelengths as follows: 330, 365, and 405 nm using a portable fiber-optic system. The fluorescence spectra were recorded in the range of 400-750 nm. A distinctive correlation between the shape of each spectrum and the level of fibrosis in the liver sample was detected. A multi-variate statistical analysis based on principal component analysis followed by linear discrimination analysis was applied to develop algorithms able to distinguish different stages of fibrosis based on the characteristics of fluorescence spectra. Pairwise comparisons were performed: F0 versus F1-F2, F1-F2 versus F3, F3 versus F4, and F1-F2 versus F4. The algorithms applied to each set of data yielded values of sensitivity and specificity that were higher than 90% and 95%, respectively, in all the analyzed cases.With this study, it is concluded that fluorescence spectroscopy can be used as a complementary tool for the assessment of liver fibrosis in liver tissue samples, which sets the stage for subsequent clinical trials.

We evaluated whether CETP and LCAT gene polymorphisms are statistically associated with the high-density lipoprotein (HDL) size distribution, the cholesterol level of HDL subclasses, and the acute coronary syndrome (ACS) susceptibility. Two CETP gene polymorphisms (rs4783961 and rs708272) and one LCAT polymorphism (rs2292318) were genotyped by 5' exonuclease TaqMan assays in 619 patients with ACS and 607 control individuals. For HDL analysis, a subgroup of 100 healthy individuals was recruited; the HDL subclasses were separated via ultracentrifugation and polyacrylamide gradient gel electrophoresis under native conditions. Under a dominant model, the G allele of the rs708272 polymorphism was associated with an increased risk of ACS (odds ratios [OR] = 1.45, corrected p-value [pCDom ] = 0.036). The linkage disequilibrium analysis showed that one of the eight possible combinations was associated with the risk of developing ACS (OR = 1.52, pC = 0.02), which suggests that it may contribute to coronary atherosclerosis. The rs708272 G allele carriers had a lower concentration of cholesterol associated with the HDL2a and HDL3a subclasses when compared with subjects carrying the A allele. Carriers of LCAT rs2292318 A allele showed a lower concentration of high-density lipoprotein-cholesterol (HDL-C) in comparison to the GG genotype; the cholesterol associated with the each one of the five HDL subclasses was significantly lower in rs2292318 A than in GG subjects. In summary, this study demonstrates that the rs708272 polymorphism is associated with a heightened risk of developing ACS. In addition, we report the association of the rs708272 and rs2292318 polymorphisms with HDL-C levels and HDL subclasses.

Liver fibrosis is a pathological process that can escalate to cirrhosis and then liver failure, a major public health concern that affect hundreds of millions of people in both developed and developing countries. Detection of liver fibrosis during its earlier stages is a matter of great importance which may allow prevention of development of cirrhosis in patients with chronic liver disease. In this work, Raman spectroscopy and thermography were evaluated to detect early pathological signs of liver fibrosis in rats in which liver fibrosis was induced using carbon tetrachloride. Results show that Raman spectra of healthy and fibrotic livers significantly differ among each other and can be classified by principal component analysis and discriminant analysis. The PCA-LDA method has a sensitivity of 100%, specificity 85% and diagnostic accuracy of 93.5%. Thermography also revealed characteristic temperature patterns for fibrotic livers compared to healthy livers. Current data suggest that Raman spectroscopy and thermography could be used to detect fibrosis in ex vivo liver samples.

Background/Aims Abnormal immune regulation and increased intestinal permeability augmenting the passage of bacterial molecules that can activate immune cells, such as monocytes/macrophages, have been reported in irritable bowel syndrome (IBS). The aim was to compare the maturation phenotype of monocytes/macrophages (CD14+) from IBS patients and controls in the presence or absence of Escherichia coli lipopolysaccharides (LPS), in vitro. Methods Mononuclear cells were isolated from peripheral blood of 20 Rome II-IBS patients and 19 controls and cultured with or without LPS for 72 hours. The maturation phenotype was examined by flow cytometry as follows: M1-Early (CD11c+CD206−), M2-Advanced (CD11c−CD206+CX3CR1+); expression of membrane markers was reported as mean fluorescence intensity (MFI). The Mann-Whitney test was used and significance was set at P < 0.05. Results In CD14+ cells, CD11c expression decreased with vs without LPS both in IBS (MFI: 8766.0 ± 730.2 vs 12 920.0 ± 949.2, P < 0.001) and controls (8233.0 ± 613.9 vs 13 750.0 ± 743.3, P < 0.001). M1-Early cells without LPS, showed lower CD11c expression in IBS than controls (MFI: 11 540.0 ± 537.5 vs 13 860.0 ± 893.7, P = 0.040), while both groups showed less CD11c in response to LPS (P < 0.01). Furthermore, the percentage of “Intermediate” (CD11c+CD206+CX3CR1+) cells without LPS, was higher in IBS than controls (IBS = 9.5 ± 1.5% vs C = 4.9 ± 1.4%, P < 0.001). Finally, fractalkine receptor (CX3CR1) expression on M2-Advanced cells was increased when treated with LPS in controls but not in IBS (P < 0.001). Conclusions The initial phase of monocyte/macrophage maturation appears to be more advanced in IBS compared to controls. However, the decreased CX3CR1 in patients with IBS, compared to controls, when stimulated with LPS suggests a state of immune activation in IBS.

The study of the effector mechanisms of T helper cells has revealed different phenotypic characteristics that can be manipulated for designing new therapeutic schemes in different pathological scenarios. Ion channels are significant targets in T lymphocyte modulation since they are closely related to their effector activity. Remarkably, some toxins produced by scorpions specifically affect the function of these membrane proteins. For that reason, these toxins are important candidates in the search for new immunomodulators. Here, the effect of two venom fractions of the scorpion Centruroides limpidus was assessed on T lymphocyte proliferation and cytokine production. The venom fractions ClF8 and ClF9 were separated by reversed-phase high-performance liquid chromatography (RP-HPLC) and cultured at 25 and 35 µg/ml with murine T lymphocytes. The results indicate that the fraction ClF8 increased both production and secretion levels of IFN-γ, IL-4, IL-17A and IL-10 by CD4+ T cells at 24 h. In contrast, fraction ClF9 only promoted the secretion of IL-17A and IL-10 at its highest concentration (35 µg/ml). Both fractions did not show any effect on T cell proliferation. Subsequent analyses by liquid chromatography-tandem mass spectrometry (LC-MS/MS) revealed seventeen toxins in the fraction ClF8 and five toxins in the fraction ClF9, most of them with voltage-gated sodium (NaScTx) and potassium (KScTx) channels as molecular targets. These toxins might probably interact with ion channels involved in T lymphocyte activity. Our findings suggest that the difference in composition between the two fractions could be related to the observed effects, and the components identified could be isolated to search for possible immunomodulatory molecules.

Recent studies have shown that P-selectin promotes the early formation of atherosclerotic plaque. The aim of the present study was to evaluate whether the SELP gene single nucleotide polymorphisms (SNPs) are associated with presence of acute coronary syndrome (ACS) and with plasma P-selectin levels in a case-control association study. The sample size was estimated for a statistical power of 80%. We genotyped three SELP (SELP Ser290Asn, SELP Leu599Val, and SELP Thr715Pro) SNPs using 5’ exonuclease TaqMan assays in 625 patients with ACS and 700 healthy controls. The associations were evaluated with logistic regressions under the co-dominant, dominant, recessive, over-dominant and additive inheritance models. The genotype contribution to the plasma P-selectin levels was evaluated by a Student’s t-test. Under different models, the SELP Ser290Asn (OR = 0.59, pCCo-Dominant = 0.047; OR = 0.59, pCDominant = 0.014; OR = 0.58, pCOver-Dominant = 0.061, and OR = 0.62, pCAdditive = 0.015) and SELP Thr715Pro (OR = 0.61, pCDominant = 0.028; OR = 0.63, pCOver-Dominant = 0.044, and OR = 0.62, pCAdditive = 0.023) SNPs were associated with a lower risk of ACS. In addition, these SNPs were associated with low plasma P-selectin levels. In summary, this study established that the SELP Ser290Asn and SELP Thr715Pro SNPs are associated with a lower risk of developing ACS and with decreased P-selectin levels in plasma in a Mexican population.

Aim: Glucose intolerance associates with M1/M2 macrophage unbalance. We thus wanted to examine the effect of M2 macrophage administration on mouse model of glucose intolerance. Materials & methods: C57BL/6 mice fed a high-fat diet (HFD) for 12 weeks and then received thrice 20 mg/kg streptozotocin (HFD-GI). Bone marrow-derived stem cells were collected from donor mice and differentiated/activated into M2 macrophages for intraperitoneal administration into HFD-GI mice. Results: M2 macrophage treatment abolished glucose intolerance independently of obesity. M2 macrophage administration increased IL-10 in visceral adipose tissue and serum, but showed no effect on serum insulin. While nitric oxide synthase-2 and arginase-1 remained unaltered, M2 macrophage treatment restored AKT phosphorylation in visceral adipose tissue. Conclusion: M2 macrophage treatment abolishes glucose intolerance by increasing IL-10 and phosphorylated AKT.

Background Acute myocardial infarction (AMI) is a leading cause of death in Mexico. Atherogenic lipid profile is a key component in AMI. Thus, it is imperative to find drug therapies able to reduce atherogenic lipids in AMI patients and prevent subsequent myocardial infarctions. Aim of the study. To investigate the effect of polypill (Sincronium®) alone or combined with beta blockers (BB) and/or thiazide diuretics (TD) on total cholesterol, triglycerides, low-density lipoproteins (LDL), high-density lipoproteins (HDL), and cardiovascular risk markers in a Mexican population with AMI. Methods Secondary AMI-prevention patients (n = 256) were included in the study and categorized into three groups depending on the drug scheme, as follows: polypill (n = 150), polypill+BB (n = 91), and polypill + BB + TD (n = 15). Lipid profile and cardiovascular risk markers were evaluated in each patient before and 6 months after drug therapy. Results The Wilcoxon-matched pairs signed rank test showed significant ∼25–30% reductions in total cholesterol, triglycerides, and LDL in the polypill group as compared to polypill + BB and polypill + BB + TD groups. On the contrary, HDL was significantly increased in polypill and polypill + BB groups. Polypill therapy showed more marked reductions in blood pressure, atherogenic index, Framingham risk score, and vascular age with respect to polypill + BB and polypill + BB + TD groups. Conclusion This study demonstrates for the first time that polypill therapy without being combined with BB and TD is effective to improve the atherogenic lipid profile and cardiovascular risk markers in AMI patients. Further studies are needed to examine the efficacy of polypill in reducing the occurrence of a second AMI in the Mexican population.

Emerging data suggest that elevated glucose may promote inflammatory activation of monocytic lineage cells with the ability to injure vascular endothelial tissue of diabetic patients, however evidence in primary human monocytes and macrophages is still insufficient. We investigated the effect of high glucose concentration on the inflammatory capacity of human macrophages in vitro and examined whether similar responses were detectable in circulating monocytes from prediabetic patients. Primary monocytes were isolated from healthy blood donors and differentiated into macrophages. Differentiated macrophages were exposed to normal levels of glucose (NG), high glucose (HG) or high mannitol as osmotic pressure control (OP) for three days. Using PCR, ELISA and flow cytometry, we found that HG macrophages showed overexpression of CD11c and inducible nitric oxide synthase as well as down-regulation of arginase-1 and interleukin (IL)-10 with respect to NG and OP macrophages. Consistent with in vitro results, circulating monocytes from hyperglycemic patients exhibited higher levels of CD11c and lower expression of CD206 than monocytes from normoglycemic controls. In subjects with hyperglycemia, elevation in CD11c(+) monocytes was associated with increased obesity, insulin resistance, and triglyceridemia as well as low serum IL-10. Our data suggest that human monocytes and macrophages undergo M1-like inflammatory polarization when exposed to high levels of glucose on in vitro culture conditions and in patients with hyperglycemia. These results demonstrate that excess glucose has direct effects on macrophage activation though the molecular mechanisms mediating such a response remain to be elucidated.

Nowadays, it is well established that biopsy is the gold standard for medical diagnosis of liver disease; however, recent studies have shown numerous discrepancies in biopsy assessment, even when it is evaluated by senior pathologists. Fluorescence spectroscopy is a tool that has been of utility in the diagnosis of different diseases based on biopsy analysis. Thus, fluorescence study of liver samples with five different degrees of fibrosis is presented. Paraffin-preserved human liver tissue was provided on white plastic cassettes by the Hospital General de Mexico “Dr. Eduardo Liceaga”. Specimens were diagnosed by two independent-senior pathologists in a double-blind test and classified into five different groups: F0, F1, F2, F3, and F4, according to the METAVIR scale for liver fibrosis. Fluorescence spectroscopy measurements were performed using three different excitation wavelengths: 385, 405, and 450 nm. Besides, diffuse reflectance spectroscopy (DRS) measurements were taken with white light to determine morphological changes in the tissue and to compare the results with medical diagnosis. The spectral analysis at excitation wavelengths of 385 nm and 405 nm showed poor correlation with medical diagnosis. Likewise, in order to discard all possible error-sources involved in the measurements, an exhaustive study was carried out; it included the determination of the fluorescence noise produced by paraffin, cassette, and the tissue itself. At 450 nm excitation wavelength, no fluorescence by the cassette was detected and noise-subtraction methods were not required, this allows a high correlation of hepatic fibrosis stages between pathological diagnosis and spectroscopic analysis. For this excitation wavelength, 89.87% correlation with DRS measurements and 82.00% with medical diagnosis were obtained. This work demonstrates that fluorescence spectroscopy using 450 nm excitation wavelength might work as a complementary tool to grade hepatic fibrosis in human liver specimens.

Objective: Growth hormone (GH) deficiency has been associated with increased steatosis but the molecular mechanism has not been fully elucidated. We investigated the effect of GH on lipid accumulation of HepG2 cells cultured on an in vitro steatosis model and examined the potential involvement of insulin-like growth factor 1 (IGF-1) as well as lipogenic and lipolytic molecules. Methods: Control and steatosis conditions were induced by culturing HepG2 cells with 5.5 or 25 mmol/l glucose for 24 h, respectively. Afterward, cells were exposed to 0, 5, 10 or 20 ng/ml GH for another 24 h. Lipid content was quantified as well as mRNA and protein levels of IGF-1, carbohydrate responsive element-binding protein (ChREBP), sterol regulatory element-binding protein 1c (SREBP1c), fatty acid synthase (FAS), carnitine palmitoyltransferase 1A (CPT1A), and peroxisome proliferator-activated receptor alpha (PPAR-alpha) by qPCR and western blot, respectively. Data were analyzed by one-way ANOVA and the Games-Howell post-hoc test. Results: In the steatosis model, HepG2 hepatocytes showed a significant 2-fold increase in lipid amount as compared to control cells. IGF-1 mRNA and protein levels were significantly increased in control cells exposed to 10 ng/ml GH, whereas high glucose abolished this effect. High glucose also significantly increased both mRNA and protein of ChREBP and FAS without having effect on SREBP1c, CPT1A and PPAR-alpha. However, GH inhibited ChREBP and FAS production, even in HepG2 hepatocytes cultured under steatosis conditions. Conclusions: Growth hormone ameliorates high glucose-induced steatosis in HepG2 cells by suppressing de novo lipogenesis via ChREBP and FAS down-regulation.

This paper presents the first results of the combination of optical techniques, through fluorescence images captured by endoscopic techniques, and imaging processing methods to give a quantitative result that will be useful to physicians to observing and following up Photodynamic Therapy (PDT) for liver cancer. The experiment was applied to an animal model using δ-aminolevulinic acid (ALA) as a photosensitizing agent, red light for the application of PDT, white light for diffuse reflectance and light of 405 nm for the capture of fluorescence photographs with endoscopic procedures on the surface of the liver. As part of the image processing, metrics such as the Euclidean distance were used and the RGB color composition components.

Introduction and Objectives: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in children and it is more prevalent in Hispanic males. The gender differences can be explained by body fat distribution, lifestyle, or sex hormone metabolism. We evaluated anthropometric and metabolic differences by gender in children with and without NAFLD. Methods: We included 194 participants (eutrophic, overweight, and individuals with obesity). The presence of NAFLD was determined using ultrasonography, and we evaluated the association between this disease with metabolic and anthropometric variables by gender. Results: The mean age was 10.64 ± 2.54 years. The frequency of NAFLD in boys was 24.51% and in girls was 11.96% (OR = 2.39; 95%CI = 1.10–5.19; p = 0.025). For girls, NAFLD was significantly associated with triglycerides (p = 0.012), homeostatic model assessment of insulin resistance (HOMA-IR) (p = 0.048), and the visceral adiposity index (VAI) (p = 0.024). The variables related to NAFLD in a gender-specific manner were body mass index (BMI) (p = 0.001), waist circumference (WC) (p

The aim of this study was to evaluate the association of rs1805193, rs5361, and rs5355 E-selectin gene single nucleotide polymorphisms (SNPs) with the risk of developing subclinical atherosclerosis (SA) in a group of Mexicans individuals. SNPs were determined by TaqMan genotyping assays in a group of 287 individuals with SA and 688 healthy controls. Under different models, the T allele of the 5′UTR G98 T (rs1805193) (OR = 1.71, 95%CI: 1.00–2.93, pCCo-dominant = 0.0006, OR = 2.02, 95%CI: 1.21–3.38, pCDominant = 0.004, and OR = 2.14, 95%CI: 1.34–3.44, pCAdditive = 0.0015) and the C allele of the Ser128Arg A561C (rs5361) (OR = 1.60, 95%CI: 0.92–2.79, pCCo-dominant = 0.012, OR = 1.78, 95%CI: 1.04–3.06, pCDominant = 0.038, and OR = 1.87, 95%CI: 1.13–3.11, pCAdditive = 0.016) polymorphisms were associated with an increased risk of development of SA. In the same way, under co-dominant model, the CT genotype of the Leu575Phe C1880T (rs5355) polymorphism was associated with an increased risk of SA as compared to CC genotype (OR = 2.34, 95%CI: 1.33–4.11, pC = 0.0035). All models were adjusted by traditional cardiovascular risk factors. In summary, this study demonstrates that the 5′UTR G98 T, Ser128Arg A561C, and Leu575Phe C1880T polymorphisms are associated with an increased risk of developing SA.

It is well known that sex hormones play an important role during Taenia solium infection; however, to our knowledge no studies exist concerning the immune response following complete or lobe-specific removal of the pituitary gland during T. solium infection. Thus, the aim of this work was to analyze in hamsters, the effects of lack of pituitary hormones on the duodenal immune response, and their impact on T. solium establishment and development. Thus, in order to achieve this goal, we perform anterior pituitary lobectomy (AL, n = 9), neurointermediate pituitary lobectomy (NIL, n = 9) and total hypophysectomy (HYPOX, n = 8), and related to the gut establishment and growth of T. solium, hematoxylin-eosin staining of duodenal tissue and immunofluorescence of duodenal cytokine expression and compared these results to the control intact (n = 8) and control infected group (n = 8). Our results indicate that 15 days post-infection, HYPOX reduces the number and size of intestinally recovered T. solium adults. Using semiquantitative immunofluorescent laser confocal microscopy, we observed that the mean intensity of duodenal IFN-γ and IL-12 Th1 cytokines was mildly expressed in the infected controls, in contrast with the high level of expression of these cytokines in the NIL infected hamsters. Likewise, the duodenum of HYPOX animals showed an increase in the expression of Th2 cytokines IL-5 and IL-6, when compared to control hamsters. Histological analysis of duodenal mucosa from HYPOX hamsters revealed an exacerbated inflammatory infiltrate located along the lamina propria and related to the presence of the parasite. We conclude that lobe-specific pituitary hormones affect differentially the T. solium development and the gut immune response.

Design of non-invasive and accurate novel methods for liver fibrosis diagnosis has gained growing interest. Different stages of liver fibrosis were induced in Wistar rats by intraperitoneally administering different doses of carbon tetrachloride. The liver fibrosis degree was conventionally determined by means of histological examination. An open-photoacoustic-cell (OPC) technique for the assessment of liver fibrosis was developed and is reported here. The OPC technique is based on the fact that the thermal diffusivity can be accurately measured by photoacoustics taking into consideration the photoacoustic signal amplitude versus the modulation frequency. This technique measures directly the heat generated in a sample, due to non-radiative de-excitation processes, following the absorption of light. The thermal diffusivity was measured with a home-made open-photoacoustic-cell system that was specially designed to perform the measurement from ex vivo liver samples. The human liver tissue showed a significant increase in the thermal diffusivity depending on the fibrosis stage. Specifically, liver samples from rats exhibiting hepatic fibrosis showed a significantly higher value of the thermal diffusivity than for control animals.

Morbid obesity has been shown to increase the risk to develop hepatic steatosis, also referred to as non-alcoholic fatty liver disease (NAFLD). Emerging evidence suggests that the severity of NAFLD may associate with increased serum levels of inflammatory markers as well as decreased concentration of mediators with anti-inflammatory actions, such as tumor necrosis factor alpha (TNF-α) and interleukin (IL) 10, respectively. We thus examined the serum levels of TNF-α and IL-10 in 102 morbidly obese women and men (body mass index 40 kg/m(2)), exhibiting different grades of NAFLD. Blood glucose, glycated hemoglobin, insulin, the homeostatic model assessment of insulin resistance (HOMA-IR), total cholesterol, triglycerides, high- and low-density lipoproteins, parameters of liver function, TNF-α, and IL-10 were measured in each subject. The stage of NAFLD was estimated by abdominal ultrasound imaging. In comparison with morbidly obese subjects without steatosis, morbidly obese patients with NAFLD showed increased age (39.23 ± 9.80 years), HOMA-IR (6.74 ± 1.62), total cholesterol (219.7 ± 9.58 mg/dl), aspartate aminotransferase (36.25 ± 3.24 UI/l), gamma-glutamyl transpeptidase (37.12 ± 3.41 UI/l), and TNF-α (37.41 ± 1.72 pg/ml) as well as decreased serum levels of IL-10 (61.05 ± 2.43 pg/ml). Interestingly, the systemic levels of TNF-α increased, while IL-10 decreased in accordance with the severity of NAFLD, which supports a role for systemic inflammatory mediators in promoting steatosis progression. Further clinical prospective studies need to be addressed to elucidate the role of TNF-α and IL-10 in the development of NAFLD while also establishing their clinical utility in the assessment of morbidly obese patients at higher risk to develop severe steatosis.

To examine the relationship of uric acid levels with parameters of systemic inflammation, metabolic dysfunction as well as anthropometric parameters and liver function tests in subjects with morbid obesity.C-reactive protein (CRP), tumour necrosis factor-alpha, and interleukin 10 (IL-10) were analyzed in 49 women and men with morbid obesity, relating these markers with uric acid, hepatic function tests, anthropometric and metabolic parameters. Metabolic parameters as serum glucose level, glycosylated hemoglobin, total cholesterol, triglycerides, high density lipoprotein and low density lipoprotein (c-LDL) as well as hepatic function parameters were measured in all subjects.-Comparing subjects with morbid obesity without hyperuricemia versus subjects with morbid obesity and hyperuricemia, an increase of total bilirubin values and gamma glutamil trans peptidase (GGT) was observed, suggesting hyperuricemia as associated with alteration of hepatic metabolism. Serum uric acid levels were statistically correlated with c-LDL, total bilirubin, albumin, GGT and CRP suggesting hyperuricemia could be associated with a dyslipidemic state, hepatic damage and increase in acute pro-inflammatory phase markers. In addition, a multiple linear regression analysis revealed that GGT and IL-10 were better predictors of the behavior of uric acid in the study population.These results suggest an -interdependent relationship among serum uric acid, CRP and IL-10 levels, which could be related to early hepatic -damage.

Background Human Pegivirus (HPgV) may have a beneficial effect on HIV disease progression in co-infected patients; however, the virologic characteristics of this infection are not well defined. In this study, we determined HPgV viremia prevalence in Mexico and provide new insights to understand HPgV infection and HPgV/HIV co-infection. Methods We analyzed and quantified 7,890 serum samples for HPgV viremia by One-Step RT-Real-Time PCR, 6,484 from healthy blood donors and 1,406 from HIV-infected patients. Data on HIV progression were obtained from patients’ records. HPgV genotyping was performed in 445 samples by nested PCR of the 5’URT region. Finite Mixture Models were used to identify clustering patterns of HPgV viremia in blood donors and co-infected antiretroviral (ART)-naive patients. Results HPgV was detected in 2.98% of blood donors and 33% of HIV patients, with a wide range of viral loads. The most prevalent genotypes were 3 (58.6%)and 2 (33.7%). HPgV viral loads from healthy blood donors and HPgV/HIV+ ART-naive co-infected patients were clustered into two component distributions, low and high, with a cut-off point of 5.07log10 and 5.06log10, respectively. High HPgV viremia was associated with improved surrogate markers of HIV infection, independent of the estimated duration of HIV infection or HIV treatment. Conclusions HPgV prevalence in Mexico was similar to that reported for other countries. The prevalent genotypes could be related to Mexico’s geographic location and ethnicity, since genotype 2 is frequent in the United States and Europe and genotype 3 in Asia and Amerindian populations. HPgV viral load demonstrated two patterns of replication, low and high. The more pronounced beneficial response observed in co-infected patients with high HPgV viremia may explain discrepancies found between other studies. Mechanisms explaining high and low HPgV replication should be explored to determine whether the persistently elevated replication depends on host or viral factors.

Recent studies have shown that P-selectin promotes the early formation of atherosclerotic plaque. The aim of the present study was to evaluate whether the SELP gene single nucleotide polymorphisms (SNPs) are associated with presence of acute coronary syndrome (ACS) and with plasma P-selectin levels in a case-control association study. The sample size was estimated for a statistical power of 80%. We genotyped three SELP (SELP Ser290Asn, SELP Leu599Val, and SELP Thr715Pro) SNPs using 5&rsquo, exonuclease TaqMan assays in 625 patients with ACS and 700 healthy controls. The associations were evaluated with logistic regressions under the co-dominant, dominant, recessive, over-dominant and additive inheritance models. The genotype contribution to the plasma P-selectin levels was evaluated by a Student&rsquo, s t-test. Under different models, the SELP Ser290Asn (OR = 0.59, pCCo-Dominant = 0.047, OR = 0.59, pCDominant = 0.014, OR = 0.58, pCOver-Dominant = 0.061, and OR = 0.62, pCAdditive = 0.015) and SELP Thr715Pro (OR = 0.61, pCDominant = 0.028, OR = 0.63, pCOver-Dominant = 0.044, and OR = 0.62, pCAdditive = 0.023) SNPs were associated with a lower risk of ACS. In addition, these SNPs were associated with low plasma P-selectin levels. In summary, this study established that the SELP Ser290Asn and SELP Thr715Pro SNPs are associated with a lower risk of developing ACS and with decreased P-selectin levels in plasma in a Mexican population.

Background: Hepatic osteodystrophy is any bone disease in patients with chronic liver disease. To measure bone mineral density (BMD) T-score by bone densitometry (BD) is used, classifying the disease in osteopenia, osteoporosis and severe osteoporosis. There are not criteria for monitoring and detection of osteodystrophy in cases of non-cholestasic cirrhosis. To determine the risk of fracture at 10 years, Fracture Risk Assessment Tool (FRAX), could be useful. Objectives: Determine the frequency of hepatic osteodystrophy in cirrhotic patients according to BD and FRAX and identify associated risk factors. Patients and methods: An observational, analytic, cross-sectional study. We included cirrhotic patients with report of DO and FRAX. Results: 52 patients were included, 38 were female (73.1%). The mean age was 12.29 ± 55.46 year-old, MELD 4.14 ± 11.71. In cholestatic etiology Mayo Score was 2.9 ± 3.31. The BMD was 0.756 ± 0.1896 mg/ cm 2 and T-score -2.34 ± 1.0. Of all patients, 26 (50%) had ranges of osteopenia and 21 (40.4%) of osteoporosis. Fracture risk with FRAX 10-year was 7.77 ± 6,713, and when we added the value of T-score fracture risk was 13.72 ± 12. Higher prevalence of cholestatic diseases in women and viral etiology in men (P = 0.006) was observed. There was significant relationship between cholestatic etiology T-score, alkaline phosphatase, and elderly and FRAXS with T-score (P =

We examined the effects of oestradiol (E2) and progesterone (P4) on cytoskeletal protein expression in the helminth Taenia crassiceps - specifically actin, tubulin and myosin. These proteins assemble into flame cells, which constitute the parasite excretory system. Total protein extracts were obtained from E2- and P4-treated T. crassiceps cysticerci and untreated controls, and analysed by one- and two-dimensional protein electrophoresis, flow cytometry, immunofluorescence and videomicroscopy. Exposure of T. crassiceps cysticerci to E2 and P4 induced differential protein expression patterns compared with untreated controls. Changes in actin, tubulin and myosin expression were confirmed by flow cytometry of parasite cells and immunofluorescence. In addition, parasite morphology was altered in response to E2 and P4 versus controls. Flame cells were primarily affected at the level of the ciliary tuft, in association with the changes in actin, tubulin and myosin. We conclude that oestradiol and progesterone act directly on T. crassiceps cysticerci, altering actin, tubulin and myosin expression and thus affecting the assembly and function of flame cells. Our results increase our understanding of several aspects of the molecular crosstalk between host and parasite, which might be useful in designing anthelmintic drugs that exclusively impair parasitic proteins which mediate cell signaling and pathogenic reproduction and establishment.

Background: The parasympathetic nervous system modulates the immune response in the abdominal-pelvic gut through the vagus nerve, which releases acetylcholine. This endogenous ligand acts on a7 nicotinic receptors expressed on immune cells. Objective: To study the mechanism of the production and regulation of cytokines in parasympathectomized and control hamsters during the development of amoebic liver abscesses (ALA) caused by Entamoeba histolytica.Methodology: Six- to 8-week-old male hamsters with and without vagotomy were used in a model of ALA. The animals were infected with trophozoites (350,000; HM1:IMSS strain) via the intrahepatic route and sacrificed at 6, 12, and 24 h and at 2, 4, and 7 days postinfection. Immune parameters were recorded at each time point using morphometric techniques including immunofluorescence and immunohistochemistry assays. These parameters included signal transducer and activator of transcription 3 (STAT3) levels, pro- and anti-inflammatory cytokine levels, and nuclear factor-γB (NFγB) activation in neutrophils and macrophages. Results: Compared to the control groups, the vagotomized (VAG) hamsters showed a significant increase in NFγB activation in neutrophils and macrophages, and higher levels of interleukin (IL)-1ß, IL-6, interferon-γ, and tumor necrosis factor-a. VAG hamsters showed an increase in the expression of IL-8 and phosphorylated STAT3 during the first 24 h postinfection as well as slightly increased levels of transforming growth factor-ß on days 2-7 postinfection. No significant differences were demonstrated in the levels of IL-10. Conclusions: These results suggest that the vagus nerve plays an important role in the regulation of inflammation during ALA formation.

AIM:It has recently been reported that the sterol regulatory element-binding transcription factors (SREBF-1c, and -2) contribute to the variation in the plasma lipids levels, which have an important role in the atherosclerotic plaque development. The aim of the present study was to evaluate whether the SREBF1c and SREBF2 gene single nucleotide polymorphisms (SNPs) are associated with plasma lipids levels and ACS susceptibility in a case-control association study. MATERIAL AND METHODS:A case-control study was carried out in 625 patients with ACS (82% men and 18% women, with a mean age of 57.97 ± 10.5 years) and 700 healthy controls (66% men and 34% women, with a mean age of 54.37 ± 7.65 years). The sample size was calculated for a statistical power of 80%. We genotyped three SREBF1c (rs2297508, rs11656665 and rs11868035) and three SREBF2 (rs2267439, rs2267443, and rs2228314) gene polymorphisms by 5' exonuclease TaqMan assays. The associations were evaluated by logistic regression under the co-dominant, dominant, recessive, over-dominant and additive inheritance models. The contribution of the genotypes on the plasma lipids levels was evaluated by Student's t-test. RESULTS:Under different models, the SREBF1c rs2297508 (OR = 1.50, pCRes = 0.03), SREBF1c rs11656665 (OR = 1.35, pCDom = 0.02 and OR = 1.26, pCAdd = 0.02) and SREBF2 rs2228314 (OR = 1.78, pCRes = 0.03, OR = 1.27, pCAdd = 0.04) SNPs were associated with higher risk of ACS. On the other hand, the SREBF1c rs11868035 SNP was associated with lower risk of ACS (OR = 0.49, pCCo-dom = 0.001, OR = 0.66, pCDom = 0.003, OR = 0.57, PRes = 0.003 and OR = 0.71, pCAdd = 0.001). There was a statistically significant association of both SREBF1c rs11656665 and rs11868035 polymorphisms with plasma triglyceride levels. CONCLUSIONS:In summary, our data suggest the association of the SREBF1c and SREBF2 SNPs with risk of developing ACS and with triglyceride levels in a Mexican population.

Aim Liver fibrosis results in a disproportion of the hepatic composition and architecture, characterized by a progressive accumulation of fibrillar proteins at the liver parenchyma. Modulated-differential scanning calorimetry (mDSC) is an experimental methodology able to determine the specific thermal signature from any biological substance, based on the variation in heat flow and heat capacity. As these physicochemical properties are directly influenced by compositional and structural changes, we decided to study the thermal behavior of the liver during fibrosis using mDSC. Methods Liver fibrosis was induced in rats by bile duct ligation or carbon tetrachloride administration. Degree of liver fibrosis was determined by histological examination using the Masson-trichrome stain, accompanied by hepatic expression of α-smooth muscle actin. The thermal analysis was performed in a modulated-differential scanning calorimeter using 20 mg of fresh liver mass. Results The liver showed a characteristic thermal signature in control animals, which progressively differed among mild (F1), moderate (F2) and advanced (F3-F4) liver fibrosis. For heat flow, the hepatic thermal signature from F3-F4 rats exhibited significant differences when compared with F1, F2 and controls. In terms of heat capacity, liver specimens provided a specific thermal signature for each stage of disease, characterized by a transition temperature onset at 95°C for controls, whereas in F1, F2 and F3-F4 animals this temperature significantly decreased to 93°C, 84°C and 75°C, respectively. Conclusion Because the liver shows a differential thermal signature according to the degree of fibrosis, mDSC could be a novel tool in the study of liver fibrosis progression.

Nonalcoholic fatty liver disease (NAFLD) ranges from steatosis to nonalcoholic steatohepatitis and cirrhosis. Liver biopsy, considered the gold standard to diagnose NAFLD, shows significantly high rates of interobserver variability. Thus there is a need to develop tools that accurately categorize mild and advanced grades of steatosis in order to identify patients at higher risk of developing chronic liver disease. Diffuse reflectance spectroscopy (DRS) has proved to be useful in grading liver fibrosis and cirrhosis, without having been implemented for steatosis. We aim to categorize early and advanced stages of liver steatosis in a methionine-choline deficient (MCD) mouse model. C57bl/6 mice are fed either methionine-choline control or MCD diet during 2 or 8 weeks to induce mild and advanced steatosis. Liver samples are obtained and steatosis is evaluated by oil red O staining. Diffuse reflectance spectra are directly measured on ex vivo liver specimens, in a wavelength range of 400 to 800 nm. DRS is able to discriminate between early or advanced steatosis and healthy hepatic tissue with negligible error while showing high average sensitivity and specificity (0.94 and 0.95, respectively). Our results suggest that liver steatosis can be accurately evaluated by DRS, highlighting the importance of applied spectroscopic methods in assessing NAFLD.