The MAHA clue - A case report

Microangiopathic hemolytic anemia (MAHA), is one of the causes of extra vascular hemolysis. It is seen in settings with pathologically altered small blood vessels. Disseminated carcinomas may rarely present as MAHA. A case of a 28 year old female with carcinoma stomach, who presented with MAHA as a first manifestation is reported. Acute onset of MAHA, may be the first manifestation of malignancy. In the absence of relatively common causes like disseminated intravascular coagulation,/Hemolytic uremic syndrome/thrombotic thrombocytopenic purpura, MAHA warrants extensive rapid investigations including bone marrow aspiration for possible metastatic deposits

Physicochemical and sensorial properties of grapefruit jams as affected by processing

Jam is an effective and tasty way of preserving fruit. Jam processing procedures as well as storage conditions and duration are important factors for jam quality. Traditional jam processing involves the application of severe thermal treatments that imply undesirable changes in the product quality characteristics such as colour, texture, flavour and nutritional and functional value. In this work, osmotic dehydration (OD) and/or microwave energy (MW) was proven as adequate to obtain jam with the typical characteristics of water content, degree Brix, pH and water activity of jam obtained by conventional thermal heating. The sensory evaluation carried out to compare the product showed that samples submitted to more intense heating treatments (conventional or MW) had significantly higher scores in colour saturation, brightness, grapefruit taste and extensibility than OD or OD+MW ones. As deduced from the obtained results, OD treatment prevents grapefruit colour changes, and mild MW heating contributes to increase the consistency and decrease the extensibility of the obtained jam. In this way, OD+MW jam was preferred by assessors mainly due to its higher consistency. The sample obtained by this procedure was stable during storage.The authors would like to thank the Ministerio de Educacion y Ciencia for the financial support given throughout the Project AGL 2005-05994. The language revision of this paper was funded by the Universidad Politecnica de Valencia, Spain.Igual Ramo, M.; García Martínez, EM.; Camacho Vidal, MM.; Martínez Navarrete, N. (2013). Physicochemical and sensorial properties of grapefruit jams as affected by processing. Food and Bioprocess Technology. 6(1):177-185. https://doi.org/10.1007/s11947-011-0696-2S17718561AENOR (2009). Sensory analysis. Methodology. Paired comparison test. UNE-EN-ISO 5495.AOAC. (2000). 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Lebensmittel-Wissenschaft und Technologie, 35, 389–392.Contreras, C., Martín-Esparza, M.-E., Martínez-Navarrete, N., & Chiralt, A. (2008). Influence of microwave application on convective drying: effects on drying kinetics, and optical and mechanical properties of apple and strawberry. Journal of Food Engineering, 88, 55–64.Dervisi, P., Lamb, J., & Zabetakis, I. (2001). High pressure processing in jam manufacture: effects on textural and color properties. Food Chemistry, 73, 85–91.Deyhim, F., Garica, K., Lopez, E., Gonzalez, J., Ino, S., Garcia, M., et al. (2006). Citrus juice modulates bone strength in male senescent rat model of osteoporosis. Nutrition, 22(5), 559–563.García-Martínez, E., Ruiz-Diaz, G., Martínez-Monzó, J., Camacho, M.-M., Martínez-Navarrete, N., & Chiralt, A. (2002). Jam manufacture with osmodehydrated fruit. Food Research International, 35, 301–306.Igual, M., García-Martínez, E., Camacho, M.-M., & Martínez-Navarrete, N. (2010a). 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Variation in the content of bioactive flavonoid in different brands of orange and grapefruit juices. Journal of Food Composition and Analysis, 19(2–3), 157–166.Wicklund, T., Rosenfeld, H.-J., Martinsen, B.-K., Sundførb, M.-W., Lea, P., Bruun, T., et al. (2005). Antioxidant capacity and colour of strawberry jam as influenced by cultivar and storage conditions. LWT-Food Science and Technology, 38(4), 387–391.Yu, L.-L., Zhou, K.-K., & Parry, J. (2005). Antioxidant properties of cold-pressed black caraway, carrot, cranberry, and hemp seed oils. Food Chemistry, 91, 723–729

Sustained proliferation in cancer: mechanisms and novel therapeutic targets

Proliferation is an important part of cancer development and progression. This is manifest by altered expression and/or activity of cell cycle related proteins. Constitutive activation of many signal transduction pathways also stimulates cell growth. Early steps in tumor development are associated with a fibrogenic response and the development of a hypoxic environment which favors the survival and proliferation of cancer stem cells. Part of the survival strategy of cancer stem cells may manifested by alterations in cell metabolism. Once tumors appear, growth and metastasis may be supported by overproduction of appropriate hormones (in hormonally dependent cancers), by promoting angiogenesis, by undergoing epithelial to mesenchymal transition, by triggering autophagy, and by taking cues from surrounding stromal cells. A number of natural compounds (e.g., curcumin, resveratrol, indole-3-carbinol, brassinin, sulforaphane, epigallocatechin-3-gallate, genistein, ellagitannins, lycopene and quercetin) have been found to inhibit one or more pathways that contribute to proliferation (e.g., hypoxia inducible factor 1, nuclear factor kappa B, phosphoinositide 3 kinase/Akt, insulin-like growth factor receptor 1, Wnt, cell cycle associated proteins, as well as androgen and estrogen receptor signaling). These data, in combination with bioinformatics analyses, will be very important for identifying signaling pathways and molecular targets that may provide early diagnostic markers and/or critical targets for the development of new drugs or drug combinations that block tumor formation and progression

Resveratrol Suppresses Constitutive Activation of AKT via Generation of ROS and Induces Apoptosis in Diffuse Large B Cell Lymphoma Cell Lines

BACKGROUND: We have recently shown that deregulation PI3-kinase/AKT survival pathway plays an important role in pathogenesis of diffuse large B cell lymphoma (DLBCL). In an attempt to identify newer therapeutic agents, we investigated the role of Resveratrol (trans-3,4', 5-trihydroxystilbene), a naturally occurring polyphenolic compound on a panel of diffuse large B-cell lymphoma (DLBCL) cells in causing inhibition of cell viability and inducing apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the action of Resveratrol on DLBCL cells and found that Resveratrol inhibited cell viability and induced apoptosis by inhibition of constitutively activated AKT and its downstream targets via generation of reactive oxygen species (ROS). Simultaneously, Resveratrol treatment of DLBCL cell lines also caused ROS dependent upregulation of DR5; and interestingly, co-treatment of DLBCL with sub-toxic doses of TRAIL and Resveratrol synergistically induced apoptosis via utilizing DR5, on the other hand, gene silencing of DR5 abolished this effect. CONCLUSION/SIGNIFICANCE: Altogether, these data suggest that Resveratrol acts as a suppressor of AKT/PKB pathway leading to apoptosis via generation of ROS and at the same time primes DLBCL cells via up-regulation of DR5 to TRAIL-mediated apoptosis. These data raise the possibility that Resveratrol may have a future therapeutic role in DLBCL and possibly other malignancies with constitutive activation of the AKT/PKB pathway

Action Mechanism of Inhibin α-Subunit on the Development of Sertoli Cells and First Wave of Spermatogenesis in Mice

Inhibin is an important marker of Sertoli cell (SC) activity in animals with impaired spermatogenesis. However, the precise relationship between inhibin and SC activity is unknown. To investigate this relationship, we partially silenced both the transcription and translation of the gene for the α-subunit of inhibin, Inha, using recombinant pshRNA vectors developed with RNAi-Ready pSIREN-RetroQ-ZsGreen Vector (Clontech Laboratories, Mountain View, Calif). We found that Inha silencing suppresses the cell-cycle regulators Cyclin D1 and Cyclin E and up-regulates the cell-cycle inhibitor P21 (as detected by Western blot analysis), thereby increasing the number of SCs in the G1 phase of the cell cycle and decreasing the amount in the S-phase of the cell cycle (as detected by flow cytometry). Inha silencing also suppressed Pdgfa, Igf1, and Kitl mRNA levels and up-regulated Tgfbrs, Inhba, Inhbb, Cyp11a1, Dhh, and Tjp1 mRNA levels (as indicated by real-time polymerase chain reaction [PCR] analysis). These findings indicate that Inha has the potential to influence the availability of the ligand inhibin and its antagonist activin in the SC in an autocrine manner and inhibit the progression of SC from G1 to S. It may also participate in the development of the blood–testis barrier, Leydig cells, and spermatogenesis through its effect on Dhh, Tjp1, Kitl, and Pdgfa. Real-time PCR and Western blot analyses of Inha, Inhba, and Inhbb mRNA and Inha levels over time show that Inha plays an important role in the formation of round spermatid during the first wave of spermatogenesis in mice

Computational analysis of expression of human embryonic stem cell-associated signatures in tumors

<p>Abstract</p> <p>Background</p> <p>The cancer stem cell model has been proposed based on the linkage between human embryonic stem cells and human cancer cells. However, the evidences supporting the cancer stem cell model remain to be collected. In this study, we extensively examined the expression of human embryonic stem cell-associated signatures including core genes, transcription factors, pathways and microRNAs in various cancers using the computational biology approach.</p> <p>Results</p> <p>We used the class comparison analysis and survival analysis algorithms to identify differentially expressed genes and their associated transcription factors, pathways and microRNAs among normal vs. tumor or good prognosis vs. poor prognosis phenotypes classes based on numerous human cancer gene expression data. We found that most of the human embryonic stem cell- associated signatures were frequently identified in the analysis, suggesting a strong linkage between human embryonic stem cells and cancer cells.</p> <p>Conclusions</p> <p>The present study revealed the close linkage between the human embryonic stem cell associated gene expression profiles and cancer-associated gene expression profiles, and therefore offered an indirect support for the cancer stem cell theory. However, many interest issues remain to be addressed further.</p

Gut microbiota and sirtuins in obesity-related inflammation and bowel dysfunction

Obesity is a chronic disease characterized by persistent low-grade inflammation with alterations in gut motility. Motor abnormalities suggest that obesity has effects on the enteric nervous system (ENS), which controls virtually all gut functions. Recent studies have revealed that the gut microbiota can affect obesity and increase inflammatory tone by modulating mucosal barrier function. Furthermore, the observation that inflammatory conditions influence the excitability of enteric neurons may add to the gut dysfunction in obesity. In this article, we discuss recent advances in understanding the role of gut microbiota and inflammation in the pathogenesis of obesity and obesity-related gastrointestinal dysfunction. The potential contribution of sirtuins in protecting or regulating the circuitry of the ENS under inflamed states is also considered

Assessment of Phenotypic and Genotypic Diversity in Elite Temperate and Tropical Sweet Sorghum Cultivars

Sweet sorghum is one of the many types of cultivated sorghums and is a promising multipurpose biofuel feedstock. The objective of this study was to assess phenotypic and genotypic diversity among 75 selected diverse sweet sorghum genotypes available at ICRISAT-Patancheru. Genotyping-by-sequencing generated 135,162 SNPs having minor allele frequencies > 0.20. Cluster analysis grouped the genotypes into three distinct clusters, with some of the sweet sorghum lines falling in distinct clusters. This grouping pattern was in conformity with available race and pedigree information. Mean performance and analysis of variance for sugar yield-related traits shows considerable variability. The results also revealed close genetic relationships between elite genotypes such as ICSV 25316, ICSV 25311, SSV 74 and ICSV 25300 that are superior for various sugar yield-associated traits like plant height, biomass, juice yield and sugar content. Not surprisingly given their pedigrees, these elite materials grouped together tightly in a single sub-cluster

Perinatal Bisphenol A Exposure Induces Chronic Inflammation in Rabbit Offspring via Modulation of Gut Bacteria and Their Metabolites

Bisphenol A (BPA) accumulates in the maturing gut and liver in utero and is known to alter gut bacterial profiles in offspring. Gut bacterial dysbiosis may contribute to chronic colonic and systemic inflammation. We hypothesized that perinatal BPA exposure-induced intestinal (and liver) inflammation in offspring is due to alterations in the microbiome and colonic metabolome. The 16S rRNA amplicon sequencing analysis revealed differences in beta diversity with a significant reduction in the relative abundances of short-chain fatty acid (SCFA) producers such as Oscillospira and Ruminococcaceae due to BPA exposure. Furthermore, BPA exposure reduced fecal SCFA levels and increased systemic lipopolysaccharide (LPS) levels. BPA exposure-increased intestinal permeability was ameliorated by the addition of SCFA in vitro. Metabolic fingerprints revealed alterations in global metabolism and amino acid metabolism. Thus, our findings indicate that perinatal BPA exposure may cause gut bacterial dysbiosis and altered metabolite profiles, particularly SCFA profiles, leading to chronic colon and liver inflammation. IMPORTANCE Emerging evidence suggests that environmental toxicants may influence inflammation-promoted chronic disease susceptibility during early life. BPA, an environmental endocrine disruptor, can transfer across the placenta and accumulate in fetal gut and liver. However, underlying mechanisms for BPA-induced colonic and liver inflammation are not fully elucidated. In this report, we show how perinatal BPA exposure in rabbits alters gut microbiota and their metabolite profiles, which leads to colonic and liver inflammation as well as to increased gut permeability as measured by elevated serum lipopolysaccharide (LPS) levels in the offspring. Also, perinatal BPA exposure leads to reduced levels of gut bacterial diversity and bacterial metabolites (short-chain fatty acids [SCFA]) and elevated gut permeability-three common early biomarkers of inflammation-promoted chronic diseases. In addition, we showed that SCFA ameliorated BPA-induced intestinal permeability in vitro. Thus, our study results suggest that correcting environmental toxicant-induced bacterial dysbiosis early in life may reduce the risk of chronic diseases later in life