scholarly journals Intestinal Absorption Profile of Three Polygala Oligosaccharide Esters in Polygalae Radix and the Effects of Other Components in Polygalae Radix on Their Absorption

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
YinYing Ba ◽  
MengLin Wang ◽  
KunFeng Zhang ◽  
QiJun Chen ◽  
JiaJia Wang ◽  
...  
Keyword(s):  
Future Research ◽  
Active Components ◽  
Sodium Caprate ◽  
P Glycoprotein ◽  
Paracellular Absorption ◽  
Underlying Mechanisms ◽  
The Relationship ◽  
Rat Gut ◽  
Human Nervous System

Oligosaccharide esters, which are among the main active components of Polygalae Radix (PR), demonstrate significant pharmacological activities in the human nervous system. In our previous research, some other constituents in PR were able to improve the bioavailability of oligosaccharide esters such as sibiricose A5 (SA5), sibiricose A6 (SA6), and 3,6′-disinapoyl sucrose (DISS), but the related components and their underlying mechanisms remain unknown. The present study aimed to investigate the intestinal absorptive profile of SA5, SA6, and DISS and the absorptive behavior influenced by the coadministration of polygalaxanthone III and total saponins of PR (TS) using an in vitro everted rat gut sac model, along with the possible mechanisms that may influence absorption. The results showed that TS could significantly enhance the absorption of SA5, SA6, and DISS monomers. Verapamil, a P-glycoprotein inhibitor, was able to elevate the absorption of SA5 and SA6, and an absorption experiment using Rho123 led us to conclude that TS influenced the absorption of SA5 and SA6 in a manner similar to that of a P-glycoprotein inhibitor. Sodium caprate, a paracellular absorption enhancer, was found to increase the absorption of SA5, SA6, and DISS. Results showed that the absorption mechanisms of SA5 and SA6 may combine active transport with paracellular passive penetration, while DISS’s absorption was dominated by paracellular passive penetration. However, the relationship between polygala saponins and the absorption of SA5, SA6, and DISS by paracellular passive penetration remain to be examined. This is the direction of our future research.

scholarly journals Role of interleukins in the pathogenesis of pulmonary fibrosis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yi Xin She ◽  
Qing Yang Yu ◽  
Xiao Xiao Tang
Keyword(s):  
Pulmonary Fibrosis ◽  
Therapeutic Strategy ◽  
Future Directions ◽  
Regulation Mechanisms ◽  
Underlying Mechanisms ◽  
Multiple Cells ◽  
The Relationship

AbstractInterleukins, a group of cytokines participating in inflammation and immune response, are proved to be involved in the formation and development of pulmonary fibrosis. In this article, we reviewed the relationship between interleukins and pulmonary fibrosis from the clinical, animal, as well as cellular levels, and discussed the underlying mechanisms in vivo and in vitro. Despite the effects of interleukin-targeted treatment on experimental pulmonary fibrosis, clinical applications are lacking and unsatisfactory. We conclude that intervening in one type of interleukins with similar functions in IPF may not be enough to stop the development of fibrosis as it involves a complex network of regulation mechanisms. Intervening interleukins combined with other existing therapy or targeting interleukins affecting multiple cells/with different functions at the same time may be one of the future directions. Furthermore, the intervention time is critical as some interleukins play different roles at different stages. Further elucidation on these aspects would provide new perspectives on both the pathogenesis mechanism, as well as the therapeutic strategy and drug development.

scholarly journals CSF1R-related leukoencephalopathy

Neurology ◽  
2018 ◽  
Vol 91 (24) ◽  
pp. 1092-1104 ◽  
Author(s):  
Takuya Konno ◽  
Koji Kasanuki ◽  
Takeshi Ikeuchi ◽  
Dennis W. Dickson ◽  
Zbigniew K. Wszolek
Keyword(s):  
White Matter ◽  
Cultured Cells ◽  
Clinical Symptoms ◽  
Current Knowledge ◽  
Gene Mutations ◽  
Future Research ◽  
Primary Role ◽  
Extrapyramidal Signs ◽  
Underlying Mechanisms

Since the discovery of CSF1R gene mutations in families with hereditary diffuse leukoencephalopathy with spheroids in 2012, more than 70 different mutations have been identified around the world. Through the analyses of mutation carriers, CSF1R-related leukoencephalopathy has been distinctly characterized clinically, radiologically, and pathologically. Typically, patients present with frontotemporal dementia-like phenotype in their 40s–50s, accompanied by motor symptoms, including pyramidal and extrapyramidal signs. Women tend to develop the clinical symptoms at a younger age than men. On brain imaging, in addition to white matter abnormalities, thinning of the corpus callosum, diffusion-restricted lesions in the white matter, and brain calcifications are hallmarks. Primary axonopathy followed by demyelination was suggested by pathology. Haploinsufficiency of colony-stimulating factor-1 receptor (CSF1R) is evident in a patient with a frameshift mutation, facilitating the establishment of Csf1r haploinsufficient mouse model. These mice develop clinical, radiologic, and pathologic phenotypes consistent with those of human patients with CSF1R mutations. In vitro, perturbation of CSF1R signaling is shown in cultured cells expressing mutant CSF1R. However, the underlying mechanisms by which CSF1R mutations selectively lead to white matter degeneration remains to be elucidated. Given that CSF1R mainly expresses in microglia, CSF1R-related leukoencephalopathy is representative of primary microgliopathies, of which microglia have a pivotal and primary role in pathogenesis. In this review, we address the current knowledge of CSF1R-related leukoencephalopathy and discuss the putative pathophysiology, with a focus on microglia, as well as future research directions.

scholarly journals Antioxidant Activity of Metabolites from Coleonema Album (Rutaceae)

2006 ◽  
Vol 1 (5) ◽  
pp. 1934578X0600100 ◽  
Author(s):  
Lindy L. Esterhuizen ◽  
Riaan Meyer ◽  
Ian A. Dubery
Keyword(s):  
Antioxidant Activity ◽  
South African ◽  
Structural Information ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Reducing Power ◽  
Active Components ◽  
Bioassay Guided Fractionation ◽  
The Relationship

Coleonema album, a member of the South African ‘Fynbos’ biome, was evaluated for its antioxidant and free radical scavenging activity. Ethanol- and acetone-based extracts from plant material obtained from two different geographical areas were analysed. A bioassay-guided fractionation methodology was followed for screening of active compounds. The 1,1-diphenyl-2-picrylhydrazyl (DPPH)-TLC method revealed the presence of a number of antioxidants which were quantified by the DPPH-spectrophotometric assay and the oxygen radical absorbance capacity (ORAC) assay. The C. album extracts possessed significant in vitro antioxidant activity, a large portion of which appeared to be contributed by the phenolic compounds. In contrast, the reducing power of the extracts could not be correlated with the observed antioxidant activity. Identification and structural information of the active components were obtained by a combination of preparative TLC and LC-MS which revealed the presence of coumarin aglycones and glycosides. The results of this study indicate that C. album contains strong antioxidants that warrant further investigation into the relationship between the structure and activity of the active coumarin metabolites.

scholarly journals The emerging role of lactate as a mediator of exercise-induced appetite suppression

2020 ◽  
Vol 319 (4) ◽  
pp. E814-E819
Author(s):  
Seth F. McCarthy ◽  
Hashim Islam ◽  
Tom J. Hazell
Keyword(s):  
Overweight And Obesity ◽  
Future Research ◽  
Ghrelin Receptor ◽  
Cellular Models ◽  
Regulatory Molecule ◽  
Blood Lactate Accumulation ◽  
Underlying Mechanisms ◽  
Exercise Induced

Lactate, a molecule originally considered metabolic waste, is now associated with a number of important physiological functions. Although the roles of lactate as a signaling molecule, fuel source, and gluconeogenic substrate have garnered significant attention in recent reviews, a relatively underexplored and emerging role of lactate is its control of energy intake (EI). To expand our understanding of the physiological roles of lactate, we present evidence from early infusion studies demonstrating the ability of lactate to suppress EI in both rodents and humans. We then discuss findings from recent human studies that have utilized exercise intensity and/or sodium bicarbonate supplementation to modulate endogenous lactate and examine its impact on appetite regulation. These studies consistently demonstrate that greater blood lactate accumulation is associated with greater suppression of the hunger hormone ghrelin and subjective appetite, thereby supporting a role of lactate in the control of EI. To stimulate future research investigating the role of lactate as an appetite-regulatory molecule, we also highlight potential underlying mechanisms explaining the appetite-suppressive effects of lactate using evidence from rodent and in vitro cellular models. Specifically, we discuss the ability of lactate to 1) inhibit the secretory function of ghrelin producing gastric cells, 2) modulate the signaling cascades that control hypothalamic neuropeptide expression/release, and 3) inhibit signaling through the ghrelin receptor in the hypothalamus. Unravelling the role of lactate as an appetite-regulatory molecule can shed important insight into the regulation of EI, thereby contributing to the development of interventions aimed at combatting overweight and obesity.

Conclusions and recommendations from the Helene Harris Memorial Trust Fourth Biennial International Forum on Ovarian Cancer 11–14 May 1993, Toronto, Canada

1994 ◽  
Vol 4 (2) ◽  
pp. 135-143 ◽  
Author(s):  
T. Blackett ◽  
F. Sharp
Keyword(s):  
Ovarian Cancer ◽  
Tumor Suppressor Genes ◽  
Malignant Tumors ◽  
Full Range ◽  
Brca1 Gene ◽  
Future Research ◽  
Relationship Of ◽  
The Relationship

The Helene Harris Memorial Trust organizes biennial international meetings of leading clinicians and scientists to discuss progress in the understanding and treatment of ovarian cancer. The conclusions of this meeting, together with recommendations for future research are published as a guide to others working in this field.The 107 conclusions and recommendations presented cover the full range of current topics in ovarian cancer research including the biology of early and borderline tumors, the relationship of benign to malignant tumors,in vitromodels, the role of cytokines, genetic epidemiology, oncogenes and tumor suppressor genes, allele loss, localization of the BRCA1 gene, DNA ploidy in prognosis, the therapeutic use of interferon, platinum and taxoid drugs, screening with panels of tumor antigensm immunotherapy and potenial for gene therapy.

scholarly journals Dose-Dependent Beneficial Effects of Tryptophan and Its Derived Metabolites on Akkermansia In Vitro: A Preliminary Prospective Study

2021 ◽  
Vol 9 (7) ◽  
pp. 1511
Author(s):  
Jia Yin ◽  
Yujie Song ◽  
Yaozhong Hu ◽  
Yuanyifei Wang ◽  
Bowei Zhang ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Physiological Function ◽  
Tryptophan Metabolism ◽  
Future Research ◽  
Beneficial Effects ◽  
First Time ◽  
The Relationship ◽  
Dose Dependent ◽  
Indole 3 Acetic Acid

Akkermansia muciniphila, a potential probiotic, has been proven to lessen the effects of several diseases. As established, the relative abundance of Akkermansia is positively correlated with tryptophan metabolism. However, the reciprocal interaction between tryptophan and Akkemansia is still unclear. Herein, for the first time, the possible effects of tryptophan and its derived metabolites on A. muciniphila were preliminarily investigated, including growth, physiological function, and metabolism. Obtained results suggested that 0.4 g/L of tryptophan treatment could significantly promote the growth of A. muciniphila. Notably, when grown in BHI with 0.8 g/L of tryptophan, the hydrophobicity and adhesion of A. muciniphila were significantly improved, potentially due to the increase in the rate of cell division. Furthermore, A. muciniphila metabolized tryptophan to indole, indole-3-acetic acid, indole-3-carboxaldehyde, and indole-3-lactic acid. Indoles produced by gut microbiota could significantly promote the growth of A. muciniphila. These results could provide a valuable reference for future research on the relationship between tryptophan metabolism and A. muciniphila.

scholarly journals Complete genomes of the eukaryotic poultry parasite Histomonas meleagridis: linking sequence analysis with virulence / attenuation

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Nicola Palmieri ◽  
Marcelo de Jesus Ramires ◽  
Michael Hess ◽  
Ivana Bilic
Keyword(s):  
Trichomonas Vaginalis ◽  
Sequence Data ◽  
Protozoan Parasite ◽  
Whole Genome Sequence ◽  
Future Research ◽  
Specific Gene ◽  
Base Level ◽  
Virulence Attenuation ◽  
Underlying Mechanisms

Abstract Background Histomonas meleagridis is a protozoan parasite and the causative agent of histomonosis, an important poultry disease whose significance is underlined by the absence of any treatment and prophylaxis. The recent successful in vitro attenuation of the parasite urges questions about the underlying mechanisms. Results Whole genome sequence data from a virulent and an attenuated strain originating from the same parental lineage of H. meleagridis were recruited using Oxford Nanopore Technology (ONT) and Illumina platforms, which were combined to generate megabase-sized contigs with high base-level accuracy. Inspecting the genomes for differences identified two substantial deletions within a coding sequence of the attenuated strain. Additionally, one single nucleotide polymorphism (SNP) and indel targeting coding sequences caused the formation of premature stop codons, which resulted in the truncation of two genes in the attenuated strain. Furthermore, the genome of H. meleagridis was used for characterizing protein classes of clinical relevance for parasitic protists. The comparative analysis with the genomes of Trichomonas vaginalis, Tritrichomonas foetus and Entamoeba histolytica identified ~ 2700 lineage-specific gene losses and 9 gene family expansions in the H. meleagridis lineage. Conclusions Taken as a whole, the obtained data provide the first hints to understand the molecular basis of attenuation in H. meleagridis and constitute a genomics platform for future research on this important poultry pathogen.

scholarly journals Physiological Correlates of Maternal Responsivity in Mothers of Preschoolers With Fragile X Syndrome

2016 ◽  
Vol 121 (2) ◽  
pp. 111-120 ◽  
Author(s):  
Ashley N. Robinson ◽  
Jane E. Roberts ◽  
Nancy C. Brady ◽  
Samuel D. McQuillin ◽  
Steven F. Warren
Keyword(s):  
Fragile X Syndrome ◽  
Family Cohesion ◽  
Fragile X ◽  
Child Outcomes ◽  
Age Effect ◽  
Future Research ◽  
Maternal Responsiveness ◽  
Maternal Responsivity ◽  
Underlying Mechanisms ◽  
The Relationship

Abstract The present study examined the relationship between salivary cortisol and maternal responsiveness in mothers of boys with fragile X syndrome (FXS). Maternal responsivity is strongly associated with child outcomes, and children with FXS are at risk for compromised development due to intellectual disability and problem behavior. Increased understanding of the nature and underlying mechanisms of maternal responsivity in FXS is important to optimize outcomes in children with FXS and contribute to improved family cohesion. Data from 36 mother-child dyads indicated a complex age effect with elevated cortisol levels associated with high maternal responsivity scores when children are young and low responsivity scores when children are older. Implications of these findings and directions for future research are discussed.

scholarly journals Contrasting multilevel relationships between behavior and body mass in blue tit nestlings

2020 ◽  
Vol 31 (3) ◽  
pp. 702-710 ◽  
Author(s):  
Barbara Class ◽  
Jon Brommer
Keyword(s):  
Body Mass ◽  
Future Research ◽  
Blue Tit ◽  
Environmental Correlations ◽  
Underlying Mechanisms ◽  
Opposing Effects ◽  
And Behavior ◽  
The Relationship ◽  
Genetic Integration ◽  
Different Levels

Abstract Repeatable behaviors (i.e., animal personality) are pervasive in the animal kingdom and various mechanisms have been proposed to explain their existence. Genetic and nongenetic mechanisms, which can be equally important, predict correlations between behavior and body mass on different levels (e.g., genetic and environmental) of variation. We investigated multilevel relationships between body mass measured on weeks 1, 2, and 3 and three behavioral responses to handling, measured on week 3, which form a behavioral syndrome in wild blue tit nestlings. Using 7 years of data and quantitative genetic models, we find that all behaviors and body mass on week 3 are heritable (h2 = 0.18–0.23) and genetically correlated, whereas earlier body masses are not heritable. We also find evidence for environmental correlations between body masses and behaviors. Interestingly, these environmental correlations have different signs for early and late body masses. Altogether, these findings indicate genetic integration between body mass and behavior and illustrate the impacts of early environmental factors and environmentally mediated growth trajectory on behaviors expressed later in life. This study, therefore, suggests that the relationship between personality and body mass in developing individuals is due to various underlying mechanisms, which can have opposing effects. Future research on the link between behavior and body mass would benefit from considering these multiple mechanisms simultaneously.

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