Miracle-dz/UniFAR-FTUs huggingface dataset:
Kaempferol Alleviates Oxidative Stress and Apoptosis Through Mitochondria-dependent Pathway During Lung Ischemia-Reperfusion Injury

In previous study, we reported that kaempferol ameliorates significantly lung ischemia-reperfusion injury (LIRI), and may be achieved by targeting the SIRT 1 pathway. This study further explored the anti-LIRI mechanism of kaempferol. In vitro, the rat alveolar epithelial cells L2 was cultured and subjected to anoxia/reoxygenation (A/R) insult. In vivo, SD rats were operated to establish LIRI model. The related indicators of oxidative stress and apoptosis in L2 cells and rats lung tissues were detected. Results showed that kaempferol pre-treatment significantly increased the cell viability, improved mitochondrial membrane potential, inhibited the opening of mitochondrial permeability transition pores, reduced the levels of oxidative stress and apoptosis, increased the expressions of Bcl-2 and mitochondrial cytochrome c, and decreased the expressions of Bax and cytoplasmic cytochrome c in L2 cells after A/R insult. In vivo, kaempferol improved the pathological injury, inhibited the levels of oxidative stress and apoptosis, increased the expressions of Bcl-2 and mitochondrial cytochrome c, and decreased the expressions of Bax and cytoplasmic cytochrome c in rats lung tissues after I/R. However, the aforementioned effects of kaempferol were significantly attenuated by the SIRT 1 inhibitor EX527 or the PGC-1α inhibitor SR-18292. What’s more, SR-18292 has not reversed the effect of kaempferol on increasing the protein activity of SIRT 1. Above results suggest that kaempferol ameliorates LIRI by improving mitochondrial function, reducing oxidative stress and inhibiting cell apoptosis. Its molecular mechanism of action includes the SIRT 1/PGC-1α/mitochondria signaling pathway.
Storytelling on Oral Grounds: Viewpoint Alignment and Perspective Taking in Narrative Discourse

In this paper, we seek to explain the power of perspective taking in narrative discourse by turning to research on the oral foundations of storytelling in human communication and language. We argue that narratives function through a central process of alignment between the viewpoints of narrator, hearer/reader, and character and develop an analytical framework that is capable of generating general claims about the processes and outcomes of narrative discourse while flexibly accounting for the great linguistic variability both across and within stories. The central propositions of this viewpoint alignment framework are that the distance between the viewpoints of participants in the narrative construal – narrator, character, reader – is dynamic and regulated by linguistic choices as well as contextual factors. Fundamentally, viewpoint alignment is grounded in oral narrative interaction and, from this conversation, transferred to the written narrative situation, varying between demonstration and invasion of the narrative subjects and guiding readers’ route of processing the narrative (experiential versus reflective). Our claim is that variations in viewpoint alignment are functional to the communicative context and intended outcomes of narratives. This is illustrated with the analysis of a corporate journalistic narrative that comprises both interactional and non-interactional aspects of storytelling. The concept of viewpoint alignment further explains the oral fundaments of narrative discourse in conversational storytelling and poses new questions on the relation between the dynamic processing of stories on the one hand and their static outcomes on the other.
Polyphosphazenes as Adjuvants for Animal Vaccines and Other Medical Applications

Polyphosphazenes are a class of experimental adjuvants that have shown great versatility as vaccine adjuvants in many animal species ranging from laboratory rodents to large animal species. Their adjuvant activity has shown promising results with numerous viral and bacterial antigens, as well as with crude and purified antigens. Vaccines adjuvanted with polyphosphazenes can be delivered via systemic and mucosal administration including respiratory, oral, rectal, and intravaginal routes. Polyphosphazenes can be used in combination with other adjuvants, further enhancing immune responses to antigens. The mechanisms of action of polyphosphazenes have not fully been defined, but several systematic studies have suggested that they act primarily by activating innate immunity. In the present review, we will highlight progress in the development of polyphosphazenes as adjuvants in animals and their other medical applications.
Comparative Study of Free-Roaming Domestic Dog Management and Roaming Behavior Across Four Countries: Chad, Guatemala, Indonesia, and Uganda

Dogs play a major role in public health because of potential transmission of zoonotic diseases, such as rabies. Dog roaming behavior has been studied worldwide, including countries in Asia, Latin America, and Oceania, while studies on dog roaming behavior are lacking in Africa. Many of those studies investigated potential drivers for roaming, which could be used to refine disease control measures. However, it appears that results are often contradictory between countries, which could be caused by differences in study design or the influence of context-specific factors. Comparative studies on dog roaming behavior are needed to better understand domestic dog roaming behavior and address these discrepancies. The aim of this study was to investigate dog demography, management, and roaming behavior across four countries: Chad, Guatemala, Indonesia, and Uganda. We equipped 773 dogs with georeferenced contact sensors (106 in Chad, 303 in Guatemala, 217 in Indonesia, and 149 in Uganda) and interviewed the owners to collect information about the dog [e.g., sex, age, body condition score (BCS)] and its management (e.g., role of the dog, origin of the dog, owner-mediated transportation, confinement, vaccination, and feeding practices). Dog home range was computed using the biased random bridge method, and the core and extended home range sizes were considered. Using an AIC-based approach to select variables, country-specific linear models were developed to identify potential predictors for roaming. We highlighted similarities and differences in term of demography, dog management, and roaming behavior between countries. The median of the core home range size was 0.30 ha (95% range: 0.17–0.92 ha) in Chad, 0.33 ha (0.17–1.1 ha) in Guatemala, 0.30 ha (0.20–0.61 ha) in Indonesia, and 0.25 ha (0.15–0.72 ha) in Uganda. The median of the extended home range size was 7.7 ha (95% range: 1.1–103 ha) in Chad, 5.7 ha (1.5–27.5 ha) in Guatemala, 5.6 ha (1.6–26.5 ha) in Indonesia, and 5.7 ha (1.3–19.1 ha) in Uganda. Factors having a significant impact on the home range size in some of the countries included being male dog (positively), being younger than one year (negatively), being older than 6 years (negatively), having a low or a high BCS (negatively), being a hunting dog (positively), being a shepherd dog (positively), and time when the dog was not supervised or restricted (positively). However, the same outcome could have an impact in a country and no impact in another. We suggest that dog roaming behavior is complex and is closely related to the owner's socioeconomic context and transportation habits and the local environment. Free-roaming domestic dogs are not completely under human control but, contrary to wildlife, they strongly depend upon humans. This particular dog–human bound has to be better understood to explain their behavior and deal with free-roaming domestic dogs related issues.
Adsorption of the antibiotic pharmaceutical compound sulfapyridine by a long-term differently fertilized loess Chernozem

Residues of antibiotic pharmaceutical compounds (APCs) found in the environment are suspected to be translocated into the food chain and to provoke the formation of resistant microorganisms. However, the behavior of APCs in soils is largely unknown. In the present study batch experiments were carried out with sulfapyridine (SPY) and p-aminobenzoic acid (ABA) amended to two loess Chernozem samples. Due to different fertilization in the course of a long-term field experiment samples differed substantially in the concentration of organic carbon (Corg 1.6 and 2.4%) and composition of soil organic matter (SOM). APCs in soil extracts were analyzed by high performance liquid chromatography. The KF values of the Freundlich isotherm for SPY were 2.2 (1.6% Corg) and 5.5 (2.4% Corg). The Koc values were 101 and 308. The different Koc values indicated that not only the quantity but also the composition of SOM affected the SPY adsorption. Adsorption of SPY was substantially higher in moist than in air-dry soil. ABA, consisting of a carboxyl group instead of the sulfonamide group substituted with a N-heterocycle, was much less adsorbed than SPY (KF 0.2). From this it was concluded that the N-heterocycle significantly contributed to the adsorption of SPY. Adsorption des pharmazeutischen Antibiotikums Sulfapyridin an langjahrig unterschiedlich gedungten Loss-Tschernosem Ruckstande pharmazeutischer Antibiotika wurden bereits in der Umwelt nachgewiesen und stehen in dem Verdacht, in die Nahrungskette uberzugehen sowie die Bildung resistenter Mikroorganismenstamme zu induzieren. Das Verhalten dieser Substanzen in Boden ist jedoch weitgehend unbekannt. In der vorliegenden Arbeit wurden Batch-Versuche mit Sulfapyridin (SPY) und p-Aminobenzoesaure (ABA) durchgefuhrt. Die Substanzen wurden zu zwei Proben eines Loss-Tschernosem zugegeben. Aufgrund einer langjahrig unterschiedlichen Dungung unterschieden sich die Proben in den Gehalten an organischem Kohlenstoff (Corg) und der Zusammensetzung der organischen Bodensubstanz (OBS). Die Antibiotika wurden in Bodenextrakten mittels Hochleistungs-Flussigkeitschromatographie (HPLC) bestimmt. Fur SPY wurden KF-Werte der Freundlich Isotherme von 2,2 (1,6% Corg) bzw. 5,5 (2,4% Corg) ermittelt; die Koc-Werte lagen bei 101 und 308. Die unterschiedlichen Koc-Werte deuteten nicht nur auf einen Einfluss der Quantitat, sondern auch der Zusammensetzung der OBS auf die SPY-Adsorption hin. Die adsorbierten Gehalte von SPY waren in feuchtem Boden wesentlich hoher als in lufttrockenem. ABA wurde im Vergleich zu SPY deutlich geringer adsorbiert (KF 0,2). Das Molekul weist anstelle des an die Sulfonamidgruppe substituierten N-Heterocyclen eine Carboxylgruppe auf. Daraus wurde geschlossen, dass der N-Heterocyclus signifikant zur Adsorption von SPY beitragt.
Formation and stability kinetics of calcium phosphate–fetuin-A colloidal particles probed by time-resolved dynamic light scattering

Fetuin-A/α2-HS glycoprotein is a major systemic inhibitor of unwanted calcium phosphate deposition in the soft tissue. Fetuin-A mediates the formation of initially ∼100 nanometre sized colloidal protein–mineral particles, denoted as calciprotein particles. After a lag period, these particles rapidly grow to elongated particles of about twice the initial size. Similar particles can be generated with other acidic macromolecules as well. However, fetuin-A is more potent regarding activity and specificity of inhibition. Given the widely recognized physiological relevance of fetuin-A as an inhibitor of pathological mineralization both in vitro, in cells, in animals and in humans, and its ready availability in large quantities, fetuin-A is a prototypic model protein to investigate protein–calcium phosphate interactions and mineral colloid stabilization, respectively. Several studies have concentrated on the pathophysiological relevance and the structural details of particle formation and mineral ripening. The principles governing calciprotein particle formation and ripening are nevertheless poorly understood. Here we present a systematic and quantitative investigation by time-resolved dynamic light scattering of the three major parameters: fetuin-A concentration, mineral ion concentration and temperature. Changes in temperature had only a weak effect on calciprotein particle size. Increased mineral ion concentrations and especially increased fetuin-A concentration led to smaller particles. An increased temperature, mineral ion concentration and a reduced fetuin-A concentration, respectively, all accelerated the particle ripening process. Our investigation demonstrates that calciprotein particle formation and ripening are two separate and successive processes and that particle ripening follows Arrhenius law. Furthermore it provides concepts to control the particle size and stability.
Neutrophils: Many Ways to Die

Neutrophils or polymorphonuclear leukocytes (PMN) are key participants in the innate immune response for their ability to execute different effector functions. These cells express a vast array of membrane receptors that allow them to recognize and eliminate infectious agents effectively and respond appropriately to microenvironmental stimuli that regulate neutrophil functions, such as activation, migration, generation of reactive oxygen species, formation of neutrophil extracellular traps, and mediator secretion, among others. Currently, it has been realized that activated neutrophils can accomplish their effector functions and simultaneously activate mechanisms of cell death in response to different intracellular or extracellular factors. Although several studies have revealed similarities between the mechanisms of cell death of neutrophils and other cell types, neutrophils have distinctive properties, such as a high production of reactive oxygen species (ROS) and nitrogen species (RNS), that are important for their effector function in infections and pathologies such as cancer, autoimmune diseases, and immunodeficiencies, influencing their cell death mechanisms. The present work offers a synthesis of the conditions and molecules implicated in the regulation and activation of the processes of neutrophil death: apoptosis, autophagy, pyroptosis, necroptosis, NETosis, and necrosis. This information allows to understand the duality encountered by PMNs upon activation. The effector functions are carried out to eliminate invading pathogens, but in several instances, these functions involve activation of signaling cascades that culminate in the death of the neutrophil. This process guarantees the correct elimination of pathogenic agents, damaged or senescent cells, and the timely resolution of the inflammation that is essential for the maintenance of homeostasis in the organism. In addition, they alert the organism when the immunological system is being deregulated, promoting the activation of other cells of the immune system, such as B and T lymphocytes, which produce cytokines that potentiate the microbicide functions.
Editorial: Natural Product Epigenetic Modulators and Inhibitors

Molecular Simulations Laboratory, Department of Chemistry, University of Buea, Buea, Cameroon, Institute of Pharmacy, Martin-Luther University of Halle-Wittenberg, Halle (Saale), Germany, Institute of Botany, Technical University Dresden, Dresden, Germany, Department of Pharmaceutical Chemistry, Istanbul University Istanbul, Istanbul, Turkey, Department of Drug Chemistry and Technologies, Faculty of Pharmacy and Medicine, Sapienza University of Rome, Rome, Italy, Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
RNA-Seq Analysis Reveals the Role of Omp16 in Brucella-Infected RAW264.7 Cells

Brucellosis is an endemic zoonotic infectious disease in the majority of developing countries, which causes huge economic losses. As immunogenic and protective antigens at the surface of Brucella spp. , outer membrane proteins (Omps) are particularly attractive for developing vaccine and could have more relevant role in host–pathogen interactions. Omp16, a homolog to peptidoglycan-associated lipoproteins (Pals), is essential for Brucella survival in vitro. At present, the functions of Omp16 have been poorly studied. Here, the gene expression profile of RAW264.7 cells infected with Brucella suis vaccine strain 2 (B. suis S2) and ΔOmp16 was analyzed by RNA-seq to investigate the cellular response immediately after Brucella entry. The RNA-sequence analysis revealed that a total of 303 genes were significantly regulated by B. suis S2 24 h post-infection. Of these, 273 differentially expressed genes (DEGs) were upregulated, and 30 DEGs were downregulated. These DEGs were mainly involved in innate immune signaling pathways, including pattern recognition receptors (PRRs), proinflammatory cytokines, and chemokines by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In ΔOmp16-infected cells, the expression of 52 total cells genes was significantly upregulated and that of 9 total cells genes were downregulated compared to B. suis S2-infected RAW264.7 cells. The KEGG pathway analysis showed that several upregulated genes were proinflammatory cytokines and chemokines, such as interleukin (IL)-6, IL-11, IL-12β, C–C motif chemokine (CCL2), and CCL22. All together, we clearly demonstrate that ΔOmp16 can alter macrophage immune-related pathways to increase proinflammatory cytokines and chemokines, which provide insights into illuminating the Brucella pathogenic strategies.
Prostate-Specific Membrane Antigen (PSMA) Promotes Angiogenesis of Glioblastoma Through Interacting With ITGB4 and Regulating NF-κB Signaling Pathway

Background Glioblastoma multiforme (GBM) is the most common primary malignant tumor in the central nervous system (CNS), causing the extremely poor prognosis. Combining the role of angiogenesis in tumor progression and the role of prostate-specific membrane antigen (PSMA) in angiogenesis, this study aims to explore the functions of PSMA in GBM. Methods Clinical GBM specimens were collected from 60 patients who accepted surgical treatment in Fudan University Shanghai Cancer Center between January 2018 and June 2019. Immunohistochemical staining was used to detect PSMA and CD31 expression in GBM tissues. Prognostic significance of PSMA was evaluated by bioinformatics. Human umbilical vein endothelial cells (HUVECs) transfected with PSMA overexpression plasmids or cultured with conditioned medium collected based on GBM cells, were used for CCK8, Transwell and tube formation assays. High-throughput sequencing and immunoprecipitation were used to explore the underlying mechanism. Furthermore, the in vivo experiment had been also conducted. Results We demonstrated that PSMA was abundantly expressed in endothelium of vessels of GBM tissues but not in vessels of normal tissues, which was significantly correlated with poor prognosis. Overexpression of PSMA could promotes proliferation, invasion and tube formation ability of human umbilical vein endothelial cells (HUVECs). Moreover, U87 or U251 conditioned medium could upregulated PSMA expression and induce similar effects on phenotypes of HUVECs, all of which could be partially attenuated by 2-PMPA treatment. The mechanistic study revealed that PSMA might promote angiogenesis of GBM through interacting with Integrin β4 (ITGB4) and activating NF-κB signaling pathway. The in vivo growth of GBM could be alleviated by the treatment of 2-PMPA. Conclusion This study identified PSMA as a critical regulator in angiogenesis and progression of GBM, which might be a promising therapeutic target for GBM treatment.
Abnormal Rat Cortical Development Induced by Ventricular Injection of rHMGB1 Mimics the Pathophysiology of Human Cortical Dysplasia

Cortical dysplasia (CD) is a common cause of drug-resistant epilepsy. Increasing studies have implicated innate immunity in CD with epilepsy. However, it is unclear whether innate immune factors induce epileptogenic CD. Here, we injected recombinant human high mobility group box 1 (rHMGB1) into embryonic rat ventricles to determine whether rHMGB1 can induce epileptogenic CD with pathophysiological characteristics similar to those of human CD. Compared with controls and 0.1 μg rHMGB1-treated rats, the cortical organization was severely disrupted in the 0.2 μg rHMGB1-treated rats, and microgyria and heterotopia also emerged; additionally, disoriented and deformed neurons were observed in the cortical lesions and heterotopias. Subcortical heterotopia appeared in the white matter and the gray–white junction of the 0.2 μg rHMGB1-treated rats. Moreover, there was decreased number of neurons in layer V–VI and an increased number of astrocytes in layer I and V of the cortical lesions. And the HMGB1 antagonist dexmedetomidine alleviated the changes induced by rHMGB1. Further, we found that TLR4 and NF-κB were increased after rHMGB1 administration. In addition, the excitatory receptors, N-methyl-D-aspartate receptor 1 (NR1), 2A (NR2A), and 2B (NR2B) immunoreactivity were increased, and immunoreactivity of excitatory amino acid transporter 1 (EAAT1) and 2 (EAAT2) were reduced in 0.2 μg rHMGB1-treated rats compared with controls. While there were no differences in the glutamic acid decarboxylase 65/67 (GAD65/67) immunoreactivity between the two groups. These results indicate that the excitation of cortical lesions was significantly increased. Furthermore, electroencephalogram (EEG) showed a shorter latency of seizure onset and a higher incidence of status epilepticus in the 0.2 μg rHMGB1-treated rats; the frequency and amplitude of EEG were higher in the treated rats than controls. Intriguingly, spontaneous electrographic seizure discharges were detected in the 0.2 μg rHMGB1-treated rats after 5 months of age, and spike-wave discharges of approximately 8 Hz were the most significantly increased synchronous propagated waves throughout the general brain cortex. Taken together, these findings indicate that rHMGB1 exposure during pregnancy could contribute to the development of epileptogenic CD, which mimicked some pathophysiological characteristics of human CD.