Crystal Structure, Synthesis and Biological Activity of Ether and Ester <i>Trans</i>-Ferulic Acid Derivatives

The structures of methoxymethyl (E)-3-(4-hydroxy-3-methoxyphenyl)acrylate, 2;(E)-3-(3-methoxy-4-(methoxymethoxy)phenyl)acrylic acid, 3;methyl (E)- 3-(4-(benzyloxy)-3-methoxyphenyl)acrylate, 4;benzyl (E)-3-(4-(benzyloxy)- 3-methoxyphenyl)acrylate, 6;and (E)-3-(4-(benzyloxy)-3-methoxyphenyl)- acrylic acid, 7;were established by spectroscopic and X-ray diffraction studies. Structure 2 is a new com-pound. Compounds with free phenolic hydroxyls v.gr. methyl (E)-3-(4-hydroxy-3-methoxyphenyl)acrylate 1, 2 and ben-zyl(E)-3-(4-hydroxy-3-methoxyphenyl)acrylate 5, showed scavenging free- radical and antioxidant activity while moderate scavenging free-radical was observed in compound 3. Moderate inhibition of lipid peroxidation was observed for 7. Compound 5 exerted significant inhibition of cell growth in PC-3, K562 tumor cell lines and 4 exhibited the largest cytotoxic effect upon the K562 cell line.

Cytokine release syndrome induced by anti-programmed death-1 treatment in a psoriasis patient:A dark side of immune checkpoint inhibitors

In recent years,cancer immunotherapy has introduced novel treatments,such as monoclonal antibodies,which have facilitated targeted therapies against tumor cells.Programmed death-1(PD-1)is an immune checkpoint expressed in T cells that regulates the immune system’s activity to prevent over-activation and tissue damage caused by inflammation.However,PD-1 is also expressed in tumor cells and functions as an immune evasion mechanism,making it a therapeutic target to enhance the immune response and eliminate tumor cells.Consequently,immune checkpoint inhibitors(ICIs)have emerged as an option for certain tumor types.Nevertheless,blocking immune checkpoints can lead to immune-related adverse events(irAEs),such as psoriasis and cytokine release syndrome(CRS),as exemp-lified in the clinical case presented by Zhou et al involving a patient with adva-nced gastric cancer who received sintilimab,a monoclonal antibody targeting PD-1.Subsequently,the patient experienced exacerbation of psoriasis and CRS.The objective of this editorial article is to elucidate potential immunologic mechanisms that may contribute to the development of CRS and psoriasis in patients receiving ICIs.It is crucial to acknowledge that while ICIs offer superior safety and efficacy compared to conventional therapies,they can also manifest irAEs affecting the skin,gastrointestinal tract,or respiratory system.In severe cases,these irAEs can lead to life-threatening complications such as circulatory shock or multiorgan failure.Consequently,it is recommended that patients receiving ICIs undergo regular monitoring to identify and manage these adverse events effectively.

How inflammation influences psychiatric disease

Recent studies highlight the strong correlation between infectious diseases and the development of neuropsychiatric disorders.In this editorial,we comment on the article“Anti-infective therapy durations predict psychological stress and laparoscopic surgery quality in pelvic abscess patients”by Zhang et al,published in the recent issue of the World Journal of Psychiatry 2023;13(11):903-911.Our discussion highlighted the potential consequences of anxiety,depression,and psychosis,which are all linked to bacterial,fungal,and viral infections,which are relevant to the impact of inflammation on the sequelae in mental health as those we are observing after the coronavirus disease 2019 pandemic.We focus specifically on the immune mechanisms triggered by inflammation,the primary contributor to psychiatric complications.Importantly,pathophysiological mechanisms such as organ damage,post-injury inflammation,and infectioninduced endocrine alterations,including hypocortisolism or autoantibody formation,significantly contribute to the development of chronic low-grade inflammation,promoting the emergence or development of psychiatric alterations in susceptible individuals.As inflammation can have long-term effects on patients,a multidisciplinary treatment plan can avoid complications and debilitating health issues,and it is crucial to recognize and address the mental health implications.

Morphological and biochemical effects of weekend alcohol consumption in rats: Role of concentration and gender

AIM To examine the association between weekend alcohol consumption and the biochemical and histological alterations at two different concentrations of alcohol in both genders in rats.METHODS Wistar rats weighing 170-200 g were divided into groups as follows:(1) Control groups; and(2) weekend alcohol-consumption group: 2 d/weekly per 12 wk, at two different concentrations:(1) Group of males or females with a consumption of a solution of alcohol at 40%; and(2) group of males or females with a consumption of a solution of alcohol at 5%. At the end of the experiment, serum and liver samples were obtained. The following enzymes and metabolites were determined in serum: Alanine Aminotransferase(ALT), Aspartate Aminotransferase(AST), Lactate Dehydrogenase, and Gamma-Glutamyltransferase, and glucose, triglycerides, cholesterol, bilirubin, and albumin. Liver samples from each group were employed to analyze morphological abnormalities by light microscopy.RESULTS In all of the weekend alcohol-consumption groups, AST activity presented a significant, 10-fold rise. Regarding ALT activity, the groups with weekend alcohol consumption presented a significant increase that was six times greater. Bilirubin levels increased significantly in both groups of females. We observed a significant increase in the parameters of fatty change and inflammation due to weekend alcohol consumption. Only the group of females that consumed alcohol at 40% presented slight hepatocel ular disorganization CONCLUSION The results obtained herein provide solid evidence that weekend alcohol consumption gives rise to liver damage, demonstrated by biochemical and histological alterations, first manifested acutely, and prolonged weekend alcohol consumption can cause greater, irreversible damage.

Evaluation of Morphological Changes of <i>Aeromonas caviae</i>Sch3 Biofilm Formation under Optimal Conditions

Aeromonas is a Gram-negative bacterium that lives in aquatic habitats. It can be infective in humans. One of its remarkable attributes is the ability of biofilm formation. Many factors are involved in the construction of biofilms as has been described for Pseudomonas, Klebsiella, and Vibrio, among others. The aim of this work was to study the bacterial morphology during the establishment of biofilm through scanning electron microscopy (SEM) and transmission electron microscopy (TEM) with a modified microtiter plate assay and to determine the best conditions for the establishment of Aeromonas caviae Sch3 biolfilm in vitro. We observed several phenotypic changes, including surface appearance, size, presence of extracellular vesicles from 100 to 250 nm in diameter, and flagella. The best conditions for biofilm formation were to grow cultures at 28℃ at pH 6, as determined by the crystal violet assay. This is, to the best of our knowledge, the first study that describes the cell’s biological events involved in the establishment of biofilm formation of Aeromonas caviae Sch3 in vitro.

Multiphasic characterization of a plant growth promoting bacterial strain, Burkholderia sp.7016 and its effect on tomato growth in the field

Aiming at searching for plant growth promoting rhizobacteria (PGPR), a bacterium strain coded as 7016 was isolated from soybean rhizosphere and was characterized in the present study. It was identiifed as Burkholderia sp. based on 16S rDNA sequence analysis, as wel as phenotypic and biochemical characterizations. This bacterium presented nitrogenase activity, 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase activity and phosphate solubilizing ability;inhibited the growth of Sclerotinia sclerotiorum, Gibberel a zeae and Verticil ium dahliae;and produced smal quantities of indole acetic acid (IAA). In green house experiments, signiifcant increases in shoot height and weight, root length and weight, and stem diameter were observed on tomato plants in 30 d after inoculation with strain 7016. Result of 16S rDNA PCR-DGGE showed that 7016 survived in the rhizosphere of tomato seedlings. In the ifeld experiments, Burkholderia sp. 7016 enhanced the tomato yield and signiifcantly promoted activities of soil urease, phosphatase, sucrase, and catalase. Al these results demonstrated Burkholderia sp. 7016 as a valuable PGPR and a candidate of biofertilizer.

Cancer stem cell impact on clinical oncology

Cancer is a widespread worldwide chronic disease. In most cases, the high mortality rate from cancer correlates with a lack of clear symptoms, which results in late diagnosis for patients, and consequently, advanced tumor disease with poor probabilities for cure, since many patients will show chemo-and radio-resistance. Several mechanisms have been studied to explain chemo-and radio-resistance to anti-tumor therapies, including cell signaling pathways, anti-apoptotic mechanisms, stemness, metabolism, and cellular phenotypes. Interestingly, the presence of cancer stem cells(CSCs), which are a subset of cells within the tumors, has been related to therapy resistance. In this review, we focus on evaluating the presence of CSCs in different tumors such as breast cancer, gastric cancer, lung cancer, and hematological neoplasias, highlighting studies where CSCs were identified in patient samples. It is evident that there has been a great drive to identify the cell surface phenotypes of CSCs so that they can be used as a tool for anti-tumor therapy treatment design. We also review the potential effect of nanoparticles, drugs, natural compounds, aldehyde dehydrogenase inhibitors, cell signaling inhibitors, and antibodies to treat CSCs from specific tumors. Taken together, we present an overview of the role of CSCs in tumorigenesis and how research is advancing to target these highly tumorigenic cells to improve oncology patient outcomes.

Review of natural products with hepatoprotective effects

The liver is one of the most important organs in the body,performing a fundamental role in the regulationof diverse processes,among which the metabolism,secretion,storage,and detoxification of endogenous and exogenous substances are prominent.Due to these functions,hepatic diseases continue to be among the main threats to public health,and they remain problems throughout the world.Despite enormous advances in modern medicine,there are no completely effective drugs that stimulate hepatic function,that offer complete protection of the organ,or that help to regenerate hepatic cells.Thus,it is necessary to identify pharmaceutical alternatives for the treatment of liver diseases,with the aim of these alternatives being more effective and less toxic.The use of some plants and the consumption of different fruits have played basic roles in human health care,and diverse scientific investigations have indicated that,in those plants and fruits so identified,their beneficial effects can be attributed to the presence of chemical compounds that are called phytochemicals.The present review had as its objective the collecting of data based on research conducted into some fruits(grapefruit,cranberries,and grapes)and plants[cactus pear(nopal)and cactus pear fruit,chamomile,silymarin,and spirulina],which are consumed frequently by humans and which have demonstrated hepatoprotective capacity,as well as an analysis of a resin(propolis)and some phytochemicals extracted from fruits,plants,yeasts,and algae,which have been evaluated in different models of hepatotoxicity.

Soil total organic carbon/total nitrogen ratio as a key driver deterministically shapes diazotrophic community assemblages during the succession of biological soil crusts

The diazotrophic community in biological soil crusts(biocrusts)is the key supplier of nitrogen in dryland.To date,there is still limited information on how biocrust development influences the succession of diazotrophic community,and what are the most important factors mediating diazotrophic communities during biocrust succession.Using the high throughput nifH amplicon sequencing,the diazotrophs in soils at different developmental stages of biocrust were comparatively studied.The results evidenced the decreases of TOC/TN ratio and pH value with biocrust development.Nostoc and Scytonema were the most dominant diazotrophic genera at all biocrust stages,while Azospirillum and Bradyrhizobium were abundant only in bare soil.Diazotrophic co-occurrence networks tended to be less complex and less connected with biocrust succession.The soil TOC/TN ratio was the most dominant factor mediating diazotrophic diversity,community composition and assembly processes,while diazotrophic-diversity and NO3–-N/NH4+-N ratio were positively correlated with the nitrogenase activity during biocrust succession.This study provided novel understandings of nitrogen fixation and succession patterns of diazotrophic community,by showing the effects of biocrust succession on diazotrophic diversity,community composition,community assembly and co-occurrence networks,and recognizing TOC/TN ratio as the most dominant factor mediating diazotrophs during biocrust succession.

Hepatoprotective effect of Geranium schiedeanum against ethanol toxicity during liver regeneration

AIM: To evaluate the effect of an extract of Geranium schiedeanum(Gs) as a hepatoprotective agent against ethanol(Et OH)-induced toxicity in rats. METHODS: Male Wistar rats weighing 200-230 g were subjected to a 70% partial hepatectomy(PH); they were then divided into three groups(groups 1-3). During the experiment, animals in group 1 drank only water. The other two groups(2-3) drank an aqueous solution of Et OH(40%, v/v). Additionally, rats in group 3 received a Gs extract daily at a dose of 300 mg/kg body weight intragastically. Subsequently, to identify markers of liver damage in serum, alanine aminotransferase, aspartate aminotransferase, albumin and bilirubin were measured by colorimetric methods. Glucose, triglyceride and cholesterol concentrations were also determined. In addition, oxidative damage was estimated by measuring lipid peroxidation [using thiobarbituric-acid reactive substances(TBARS)] in both plasma and the liver and by measuring the total concentration of antioxidants in serum and the total antioxidant capacity in the liver. In addition, a liver mass gain assessment, total DNA analysis and a morpho-histological analysis of the liver from animals in all three groups were performed and compared. Finally, the number of deaths observed in the three groups was analyzed.RESULTS: Administration of the Geranium shiedeanum extract significantly reduced the unfavorable effect of ethanol on liver regeneration(restitution liver mass: PHEt OH group 60.68% vs PH-Gs-Et OH group 69.22%). This finding was congruent with the reduced levels of hepatic enzymes and the sustained or increased levels of albumin and decreased bilirubin in serum. The extract also modified the metabolic processes that regulate glucose and lipid levels, as observed from the serum measurements. Lower antioxidant levels and the liver damage induced by Et OH administration appeared to be mitigated by the extract, as observed from the TBARs(PH-Et OH group 200.14 mmol/mg vs PH-Gs-Et OH group 54.20 mmol/mg; P < 0.05), total status of antioxidants(PH-Et OH group 1.43 mmol/L vs PH-Gs-Et OH group 1.99 mmol/L; P < 0.05), total antioxidant capacity values, liver mass gain and total DNA determination(PH-Et OH group 4.80 mg/g vs PH-Gs-Et OH 9.10 mg/g; P < 0.05). Overall, these processes could be related to decreased mortality in these treated animals.CONCLUSION: The administered extract showed a hepatoprotective effect, limiting the Et OH-induced hepatotoxic effects. This effect can be related tomodulating oxido-reduction processes.

HP0953-hypothetical virulence factor overexpresion and localization during Helicobacter pylori infection of gastric epithelium

BACKGROUND The high prevalence and persistence of Helicobacter pylori(H. pylori) infection, as well as the diversity of pathologies related to it, suggest that the virulence factors used by this microorganism are varied. Moreover, as its proteome contains 340hypothetical proteins, it is important to investigate them to completely understand the mechanisms of its virulence and survival. We have previously reported that the hypothetical protein HP0953 is overexpressed during the first hours of adhesion to inert surfaces, under stress conditions, suggesting its role in the environmental survival of this bacterium and perhaps as a virulence factor.AIM To investigate the expression and localization of HP0953 during adhesion to an inert surface and against gastric(AGS) cells.METHODS Expression analysis was performed for HP0953 during H. pylori adhesion. HP0953 expression at 0,3, 12, 24, and 48 h was evaluated and compared using the Kruskal-Wallis equality-of-populations rank test. Recombinant protein was produced and used to obtain polyclonal antibodies for immunolocalization. Immunogold technique was performed on bacterial sections during adherence to inert surfaces and AGS cells, which was analyzed by transmission electron microscopy. HP0953 protein sequence was analyzed to predict the presence of a signal peptide and transmembrane helices, both provided by the ExPASy platform, and using the GLYCOPP platform for glycosylation sites. Different programs, via, I-TASSER, RaptorX, and HHalign-Kbest, were used to perform three-dimensional modeling.RESULTS HP0953 exhibited its maximum expression at 12 h of infection in gastric epithelium cells.Immunogold technique revealed HP0953 localization in the cytoplasm and accumulation in some peripheral areas of the bacterial body, with greater expression when it is close to AGS cells.Bioinformatics analysis revealed the presence of a signal peptide that interacts with the transmembrane region and then allows the release of the protein to the external environment. The programs also showed a similarity with the Tip-alpha protein of H. pylori. Tip-alpha is an exotoxin that penetrates cells and induces tumor necrosis factor alpha production, and HP0953 could have a similar function as posttranslational modification sites were found;modifications in turn require enzymes located in eukaryotic cells. Thus, to be functional, HP0953 may necessarily need to be translocated inside the cell where it can trigger different mechanisms producing cellular damage.CONCLUSION The location of HP0953 around infected cells, the probable posttranslational modifications, and its similarity to an exotoxin suggest that this protein is a virulence factor.

Cerebral dopamine neurotrophic factor transfection in dopamine neurons using neurotensin-polyplex nanoparticles reverses 6-hydroxydopamine-induced nigrostriatal neurodegeneration

Overexpression of neurotrophic factors in nigral dopamine neurons is a promising approach to reverse neurodegeneration of the nigrostriatal dopamine system,a hallmark in Parkinson's disease.The human cerebral dopamine neurotrophic factor(h CDNF)has recently emerged as a strong candidate for Parkinson's disease therapy.This study shows that h CDNF expression in dopamine neurons using the neurotensinpolyplex nanoparticle system reverses 6-hydroxydopamine-induced morphological,biochemical,and behavioral alterations.Three independent electron microscopy techniques showed that the neurotensin-polyplex nanoparticles containing the h CDNF gene,ranging in size from 20 to 150 nm,enabled the expression of a secretable h CDNF in vitro.Their injection in the substantia nigra compacta on day 21 after the 6-hydroxydopamine lesion resulted in detectable h CDNF in dopamine neurons,whose levels remained constant throughout the study in the substantia nigra compacta and striatum.Compared with the lesioned group,tyrosine hydroxylase-positive(TH^(+))nigral cell population and TH+fiber density rose in the substantia nigra compacta and striatum after h CDNF transfection.An increase inβIII-tubulin and growth-associated protein 43 phospho-S41(GAP43 p)followed TH^(+)cell recovery,as well as dopamine and its catabolite levels.Partial reversal(80%)of drugactivated circling behavior and full recovery of spontaneous motor and non-motor behavior were achieved.Brain-derived neurotrophic factor recovery in dopamine neurons that also occurred suggests its participation in the neurotrophic effects.These findings support the potential of nanoparticle-mediated h CDNF gene delivery to develop a disease-modifying treatment against Parkinson's disease.The Institutional Animal Care and Use Committee of Centro de Investigación y de Estudios Avanzados approved our experimental procedures for animal use(authorization No.162-15)on June 9,2019.

Polyphenol Oxidase Inactivation by Microwave Oven and Its Effect on Phenolic Profile of Loquat (<i>Eriobotrya japonica</i>) Fruit

The objective of this research was investigated the effect of polyphenol oxidase microwave treatment on phenolic composition, antioxidant activity and microstructure of loquat fruit. Phenolic profile of methanolic extracts prepared from fresh, and microwave-treated samples were analyzed. Antioxidant activity was also evaluated by 2,2’-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS?+) and 1,1-diphenyl-2-picrylhydrazyl (DPPH+) methods. In addition, polyphenol oxidase inactivation was carried out using a response surface methodology to establish the optimal conditions of treatment. The phenolic content of fresh mesocarp was 311 ± 0.60 mg gallic acid equivalents (GAE)/100g dry weight (DW) and that of microwave-treated mesocarp was 1230 ± 0.36 mg GAE/100g DW. Total phenolic content of water/ methanol extract significantly increases after microwave treatment rather than methanolic extract of fresh loquat. Five glycoside phenolics were identified by HPLC-DAD-MS as 3-caffeoylquinic acid, 3-p-coumaroylquinic acid, 5-caffeoylquinic acid and quercetin-3-O-sambubioside. Methanolic extract of microwave-treated mesocarp showed higher antioxidant activity than that of fresh mesocarp. Thus, polyphenol oxidase inactivation by microwave energy preserved the integrity of phenolic compounds as well as antioxidant activity in mesocarp extracts prepared from loquat fruit. It was also noted that phenolics were more abundant in the microwaved samples than in the fresh samples.

Biocompatibility and electrochemical evaluation of ZrO_(2) thin films deposited by reactive magnetron sputtering on MgZnCa alloy

Biodegradable magnesium alloys are promising candidates for temporary fracture fixation devices in orthopedics;nevertheless,its fast degradation rate at the initial stage after implantation remains as one of the main challenges to be resolved.ZrO_(2)-based coatings to reduce the degradation rate of the Mg-implants are an attractive solution since they show high biocompatibility and stability.In this work,the degradation,cytotoxicity,and antibacterial performance of ZrO_(2)thin films deposited by magnetron sputtering on a Mg-Zn-Ca alloy was evaluated.Short-term degradation of ZrO_(2)-coated and uncoated samples was assessed considering electrochemical techniques and H_(2)evolution(gas chromatography).Additionally,long term degradation was assessed by mass-loss measurements.The results showed that a 380 nm ZrO_(2)coating reduces the degradation rate and H_(2)evolution of the alloy during the initial 3 days after immersion but allows the degradation of the bare alloy for the long-term.The ZrO_(2)coating does not compromise the biocompatibility of the alloy and permits better cell adhesion and proliferation of mesenchymal stem cells directly on its surface,in comparison to the bare alloy.Finally,the ZrO_(2)coating prevents the adhesion and biofilm formation of S.aureus.

Chemical Characterisation of the Industrial Residues of the Pineapple (Ananas comosus)

In Mexico pineapple processing produces industrial residues with a high concentration of dietary fibre. The aim of this study was to quantify the constituents of the fibrous residues from the industrial processing of pineapples which exhibited low concentrations of lignin.

Serum levels of chemokines in adolescents with major depression treated with fluoxetine

BACKGROUND Major depressive disorder(MDD)is a global health issue that affects 350 million people of all ages.Although between 2%and 5.6%of affected individuals are adolescents,research on young patients is limited.The inflammatory response contributes to the onset of depression,and in adult MDD patients,symptom severity has been linked to chemokine levels.AIM To determine the differences in circulatory levels of chemokines in healthy volunteers(HVs)and adolescents with MDD,and assess the changes induced by fluoxetine consume.METHODS The 22 adolescents with MDD were monitored during the first 8 wk of clinical follow-up and clinical psychiatric evaluation was done using the Hamilton depresión rating scale(HDRS).The serum levels of monocyte chemoattractant protein-1(MCP-1),macrophage inflammatory protein(MIP)-1α,MIP-1β,interleukin(IL)-8,interferon gamma-induced protein(IP)-10,and eotaxin were measured in patients and HVs.RESULTS In all cases,significant differences were detected in circulating chemokine levels between patients before treatment and HVs(P<0.0001).All chemokines decreased at 4 wk,but only MCP-1 and IL-8 significantly differed(P<0.05)between 0 wk and 4 wk.In the patients,all chemokines rose to their initial concentrations by 8 wk vs 0 wk,but only IP-10 did so significantly(P<0.05).All patients experienced a significant decrease in HDRS scores at 4 wk(P<0.0001)and 8 wk(P<0.0001)compared with 0 wk.CONCLUSION Despite the consumption of fluoxetine,patients had significantly higher chemokine levels,even after considering the improvement in HDRS score.The high levels of eotaxin,IP-10,and IL-8 partially explain certain aspects that are affected in MDD such as cognition,memory,and learning.

Lima Bean(Phaseolus lunatus)Protein Hydrolysates with ACE-I Inhibitory Activity

Several protein sources can be used to produce bioactive peptides with angiotensin I-converting enzyme (ACE) inhibittory activity. Protein concentrates from ungerminated and germinated lima bean Phaseolus lunatus seed flours were hydrolyzed with Alcalase 2.4 L or pepsin-pancreatin sequential hydrolysis, and ACE inhibitory activity measured in the different hydrolysis treatments. Protein hydrolysate production was analyzed with a 23 factorial design with four replicates of the central treatment. Evaluated factors were protein concentrate source (ungerminated seeds, PC1;germinated seeds, PC2), enzyme/substrate ratio E/S (1/50 or 1/10) and hydrolysis time (0.5 or 2.0 h for Alcalase;1 or 3 h for pepsin-pancreatin). Degree of hydrolysis (DH) was high for the Alcalase hydrolysates (24.12% 58.94%), but the pepsin-pancreatin hydrolysates exhibited the highest ACE inhibitory activity (IC50 = 0.250 0.692 mg/mL). Under the tested conditions, the hydrolysates with the highest ACE inhibitory activity were produced with sequential pepsin-pancreatin using either PC1 at 1 h hydrolysis time and a 1/10 E/S ratio or PC2 at 1 h hydrolysis time and a 1/50 E/S ratio. Lima bean protein hydrolysates prepared with Alcalase or pepsin-pancreatin are a potential ingredient in the production of physiologically functional foods with antihypertensive activity.

Atypical antipsychotics, more than just an antipsychotic

Antipsychotics are the prescribed drugs for schizophrenia.The first substance used for antipsychotic purposes appeared in 1952 and it was a general anesthetic:chlorpromazine.The use of this drug was mainly because of its effects on violent behavior instead of sedation in patients,which“controls”the psychotic episodes and prevents psychosis relapse.Since then,pharmaceutical antipsychotics have been developed,producing second-generation or atypical drugs.These drugs arose with the synthesis of clozapine in the late‘50s,which represented(and still represent)the“guide molecule”for the development of these substances,because of its effectiveness on the symptomatology of the disease.

Microwave Dried Carrot Pomace as a Source of Fiber and Carotenoids

Carrot pomace is a major by-product obtained during the industrial juice extraction process, which is discarded contributing to environmental pollution. This residue is rich in fiber, and contains high amounts of carotenoids and phenolic compounds that could contribute to its application as functional ingredient, improving the quality of foods and helping to reduce the environmental problem. In this study, carrot pomace powders obtained by microwave or hot air drying were incorporated into cookies in order to improve their phytochemical content. Cookies were prepared using a traditional cookie recipe substituting 30% of the wheat flour for either of the carrot pomace powders. Fiber, carotenoids and phenolic compounds were determined;image analysis and acceptability of the cookies were also conducted. The substitution of 30% of wheat flour for carrot pomace powders increased 3.7 fold the total dietary fiber of cookies, from 7.13 g/100gto26.44 g/100g;accounting the 7.4% of fiber daily intake with the consumption of one cookie (7 g). A similar pattern was found in the content of carotenoids and phenolic compounds. Carrot pomace dried with microwaves had the highest amount of these bioactive compounds. β-carotene, epicatechin, gallic and ferulic acids were identified in cookies with microwave carrot pomace powder. The cookies incorporated with carrot pomace powders exhibited improved antioxidant properties because of the increase in the phytochemical content. Acceptable cookies with appealing orange color were obtained. The results indicated that the replacement of wheat flour for carrot pomace powders yielded dietary fiber enriched cookies with improved carotenoid content.

Genome-wide comparison inferred the origin and evolution of B-cell epitopes on the proteins of human influenza A virus

The novel strain H1N1 caused the outbreak of first pandemic influenza in 21 century. Now it is a common component of current seasonal influenza viruses. The recent transmission and plentiful genome sequences available provided a good opportunity to study the origin and evolution of epitopes on the proteins of human influenza virus. In the present study, the B-cell epitope compositions in the pandemic strains, circulating traditional seasonal strains, swine strains as well as highly virulent avian strain H5N1 were identified with the aid of the Immune Epitope DataBase (IEDB) and were compared at genomic level. A total of 14210 distinct sequences down-loaded from NCBI database were used for analysis. Some epitopes on proteins HA or NA, not conserved in recent seasonal strains, were found in 2009 pandemic strains but existed in the early human strains (1919-1935). The pandemic strain shared higher conserved epitopes with “bird flu” virus H5N1than classic human seasonal strains. The epitopes that could exist at common antigenic regions of HA protein are needed to further identify. The genetic exchanges between human and swine population by transmission was very active but the princepal side of the transmission could be from swine to human. These results provided valuable information on influenza A virus evolution and transmission by means of epitope analysis at genomic level.