23 research outputs found
Mechanisms for Colonic Mucosal Wound Repair
No full textThe studies outlined in this thesis provide several new insights into mesenchymal and epithelial pathways necessary for colonic mucosal repair. We found that maximal expression of Ptgs2 in mesenchymal stromal cells was required for epithelial restitution and smooth muscle survival after colonic biopsy injury. We screened and identified Igf2bp1 as a novel Ptgs2 mRNA-binding protein required for maximal Ptgs2 expression. We next determined that the prostaglandin PGI2 was necessary to prevent smooth muscle necrosis. PGI2 functioned in our model by stimulating angiogenesis and preventing wound bed hypoxia. To rescue the angiogenesis and muscle loss defects in PGI2 receptor-deficient mice, we systemically and locally injected colonic mesenchymal stem cells. In contrast with systemically-injected cells, locally-injected MSCs migrated to wounds and stimulated repair. We next screened wound-associated epithelial cells and identified mesothelin as an epithelial gene expressed only after biopsy injury. We found that mesothelin was required for granulation tissue formation after colonic biopsy injury and was required for maximal polyp growth in APCMin/+ mice. Overall, this work describes mesenchymal- and epithelial-derived factors that are important for wound repair after colonic mucosal injury. Understanding the complex interactions for colonic wound repair will lead to better treatments for intestinal diseases such as inflammatory bowel disease
Infanzia e guerra: Kadono Eiko
No full textL’articolo fa una panoramica della letteratura giapponese per l’infanzia legata alla Seconda Guerra Mondiale, presentando i vari filoni in cui la produzione viene suddivisa dagli studiosi che parlano di sensō jidōbungaku, letteratura di guerra per l’infanzia, termine usato a proposito delle opere pacifiste e contro la guerra, includendo tematiche come i bombardamenti aerei, in particolare quelli su Tokyo nel marzo del 1945, lo sfollamento dei bambini, la vita nei territori stranieri occupati dai giapponesi, l’assalto a Okinawa e la convivenza con le forze alleate e, naturalmente, la bomba atomica che, lasciata in disparte subito dopo la sconfitta per problemi di censura, (Hasegawa, 2017, 20) appare poi in modo significativo negli anni successivi senza determinare però un filone a se stante come accade nella produzione per adulti.
Lo studio si concentra quindi su Kadono Eiko (1935-), pluripremiata scrittrice per l’infanzia, vincitrice dell’Hans Christian Andersen Author Award (2018), nota al grande pubblico per il romanzo Majo no takkyūbin (Kiki consegne a domicilio, 1985) di cui la trasposizione cinematografica è uscita nel 1989 a opera di Miyazaki Hayao (1941-). In particolare viene preso in considerazione il romanzo Tonneru no mori 1945 (Il tunnel attraverso la foresta 1945, 2015), mai tradotto all’estero, basato sull’esperienza di Kadono nel periodo della guerra, allo scopo di comprendere cosa l’abbia spinta a scrivere su questo tema allontanandosi dalle storie allegre e fantastiche che avevano caratterizzato la maggior parte della sua produzione.
L’analisi dell’opera mostra gli aspetti legati alla tradizione giapponese sottolineando il rapporto speciale con la natura ricordata spesso dall’autrice. Inoltre ne vengono evidenziati la posizione e il valore all’interno della produzione di sensō jidōbungaku rifiorita in anni recenti dopo il triplice disastro del Tohoku del 2011, in risposta alle scelte politiche e alla paura dell’oblio dei fatti accaduti. Consapevole della potenzialità della letteratura di trasmettere la memoria degli avvenimenti passati con più forza rispetto ai libri di storia e quindi di avere il dovere di farlo nei confronti delle generazioni future. Kadono rientra fra gli autori in età avanzata che, da testimoni, si sentono in dovere di raccontare della propria esperienza, perché non si ripeta nuovamente quello che è successo ad altri bambini
Mesenchymal stem cell therapy of intestinal disease: are their effects systemic or localized?
No full textIL-6 stimulates intestinal epithelial proliferation and repair after injury
No full textIL-6 is a pleiotropic cytokine often associated with inflammation. Inhibition of this pathway has led to successful treatment of rheumatoid arthritis, but one unforeseen potential complication of anti-IL-6 therapy is bowel perforation. Within the intestine, IL-6 has been shown to prevent epithelial apoptosis during prolonged inflammation. The role of IL-6 in the intestine during an initial inflammatory insult is unknown. Here, we evaluate the role of IL-6 at the onset of an inflammatory injury. Using two murine models of bowel injury - wound by biopsy and bacterial triggered colitis - we demonstrated that IL-6 is induced soon after injury by multiple cell types including intraepithelial lymphocytes. Inhibition of IL-6 resulted in impaired wound healing due to decreased epithelial proliferation. Using intestinal tissue obtained from patients who underwent surgical resection of the colon due to traumatic perforation, we observed cells with detectable IL-6 within the area of perforation and not at distant sites. Our data demonstrate the important role of IL-6 produced in part by intraepithelial lymphocytes at the onset of an inflammatory injury for epithelial proliferation and wound repair
The Role of Prosody in Making Presentations
No full textBakalaura darbā aplūkota prosodijas loma biznesa prezentāciju veidošanā. Šī darba mērķis bija pētīt retorikas un prozodijas elementu klātbūtni un pielietojumu pārliecinošā lietišķā prezentācijā. Pētījumā tika analizēta atbilstoša literatūra par prezentāciju kā žanru un runas prozodiju, atlasīta viena lietišķa prezentācija, analizētas retoriskās un prozodiskās iezīmes un to ietekme uz pārliecinātības līmeni dotajā prezentācijā. Izpētes rezultātā tika atklāts, ka analizētajā prezentācijā prezentētājs pārsvarā izmantojis augstos krītošos toņus, prasmīgi pielietojis ritmu, dažādu garumu pauses un dinamisku tempu. Prezentācijas analīze ļāva darba autorei secināt, ka prozodijas un retorikas elementu prasmīgs pielietojums būtiski ietekmē runātāja prezenēšanas manieri pasniedzot tēmu pārliecinošā veidā.The present bachelor thesis deals with the role of prosody in making business presentations. The aim of the paper was to study the presence and the application of both rhetoric and prosodic elements in a persuasive business presentation. The research was carried out by reading relevant literature on presentation as a genre and prosody of speech, selecting one business presentation, analysing the prosodic features and their impact on the level of persuasiveness in the given presentation. The results of the research revealed that, in the presentation analysed, the presenter has mainly used high falling tones, skillfully applied rhythm, pauses of various lengths and dynamic tempo. The analysis of the presentation allowed the author of the present paper to conclude that the skillful application of the prosodic and rhetoric features have a major impact on the presenter’s manner of presenting the subject matter in a persuasive way
IL-6 expression was increased in human colons at sites of perforation.
No full text<p>Tissue that was surgically resected from patients who suffered large bowel perforation was evaluated for IL-6 expression by <i>in situ</i> hybridization. Eleven cases were evaluated (8 males with trauma due to gun-shot wounds, ages 16–33; 1 female surgical trauma, age 45; and 2 females with diverticulitis, ages 72 and 79). (A) Representative staining from a patient with diverticulitis is shown at 20X and 100X, respectively. Bars = 100 µm. Arrows indicate IL-6+ cells with lymphocyte morphology. (B) Four high-powered fields with well-oriented crypts were evaluated for IL-6+ cells in the epithelial layer at the site of perforation and at the distal resection margin. The average ratio of IL-6+ cells in the perforation versus distal site ± SEM was shown. An unpaired student's t-test was used for statistical analysis; *, <i>P</i> = 0.02.</p
IL-6 promoted intestinal epithelial proliferation in wound biopsy model.
No full text<p>(A) WT mice were biopsy injured in the distal colon. Plot of the relative levels of IL-6 mRNA expression in the wound bed (relative to uninjured tissue) for various times after injury. N = 2–3 WT mice with a total of 4-6 wounds/time point. Data were shown as average ± SEM. One-way analysis of variance: F = 5.68, <i>P</i><0.01 (B) Cartoon depicting the microanatomy of a wound at day six post-biopsy; AC = adjacent crypts (green area); WC = wound channels (blue area); WAE = wound-associated epithelium overlying the wound bed (pink area). (C) Colonic sections of wounds from <i>IL-6<sup>+/−</sup></i> and <i>IL-6<sup>-/-</sup></i> mice at day six post-injury stained with mAb to BrdU (labels S-phase cells, red), mAb to β-catenin (labels epithelium, green), and bis-benzimide (nuclei, blue). Bars = 500 µm. (D) Quantification of the number of BrdU positive cells/wound adjacent crypts. Data were graphed as average ± SEM. One way analysis of variance: F = 10.5, p<0.0001. Means with different letters are significantly different by Bonferroni's multiple comparison test.</p
Inhibition of IL-6 resulted in more severe colitis and inhibition of intestinal epithelial proliferation.
No full text<p>Colitis was induced in <i>dnKO</i> and <i>IL-10rb<sup>+/-</sup></i> littermate controls by co-housing. On day zero and three times weekly, mice were injected intraperitoneally with 500 µg of either anti-IL-6 mAb or control IgG mAb. Two independent experiments were performed with 8-9 mice/group. (A) Plot of the average percent of starting weight ± SEM shown for indicated groups of mice. Mice were weighed every three days. (B) Representative H+E stained sections of descending colons at day 9 post co-housing. Bars = 500 µm. Black dotted lines outline remaining crypts in the <i>dnKO</i> anti-IL-6 mAb treated mouse histology. (C) Graph of the average number of descending colonic crypts per high-powered field ± SEM. (D) At day 9 post-co-housing, mice were injected with BrdU one hour before sacrifice. Representative colonic sections stained with mAb to BrdU and detected with fluorescently conjugated antibodies were shown. The white dotted lines delineate crypts. Bars = 100 µm. (E) Graph of the average number ± SEM of BrdU positive cells per crypt. (F) Graph of the average ± SEM number of apoptotic bodies/crypt. One-way analysis of variance: (A) F = 3.5, <i>P</i><0.05 (for day 9 weights); (C) F = 57.36, <i>P</i><0.0001; (E) F = 17.92, <i>P</i><0.0001; (F) F = 10.87, <i>P</i><0.0001. Means with different letters are significantly different by Bonferroni's multiple comparison test.</p
JNK-mediated disruption of bile acid homeostasis promotes intrahepatic cholangiocarcinoma
No full textFull author list omitted for brevity. For the full list of authors, see article.Metabolic stress causes activation of the cJun NH2-terminal kinase (JNK) signal transduction pathway. It is established that one consequence of JNK activation is the development of insulin resistance and hepatic steatosis through inhibition of the transcription factor PPARalpha. Indeed, JNK1/2 deficiency in hepatocytes protects against the development of steatosis, suggesting that JNK inhibition represents a possible treatment for this disease. However, the long-term consequences of JNK inhibition have not been evaluated. Here we demonstrate that hepatic JNK controls bile acid production. We found that hepatic JNK deficiency alters cholesterol metabolism and bile acid synthesis, conjugation, and transport, resulting in cholestasis, increased cholangiocyte proliferation, and intrahepatic cholangiocarcinoma. Gene ablation studies confirmed that PPARalpha mediated these effects of JNK in hepatocytes. This analysis highlights potential consequences of long-term use of JNK inhibitors for the treatment of metabolic syndrome
Intraepithelial lymphocytes were a source of IL-6 early after injury.
No full text<p>(A) Biopsy of the colon mucosa was performed in WT mice to create small wounds. IL-6 expression in the wound bed and adjacent tissue was evaluated by <i>in situ</i> hybridization one day after biopsy. Representative images were shown. Bars = 200 µm. Colored bars above wound images indicate areas of the wound bed as depicted in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0114195#pone-0114195-g004" target="_blank">Figure 4B</a>. (B) Co-localization by immunofluorescence was performed for IL-6 (red), CD3ε (green), and bis-benzimide (blue) on colon tissue from <i>dnKO</i> mice at day 6 after co-housing. Representative staining was shown at 63X. Bar = 200 µm. (C) Epithelial cells were harvested from <i>dnKO</i> mice on day 6 after co-housing, stained for T cell markers and IL-6, and assessed by flow cytometry. Representative dot plots were shown. (D, E) CD3+ CD4- CD8- IELs were harvested from WT mice and stimulated <i>ex vivo</i> with 10 ng/ml PMA and 1 µg/ml ionamycin for 5 hours. (D) RNA was collected and evaluated by qRT-PCR for IL-6 expression. (E) Culture supernatants were harvested and evaluated for secreted IL-6 by electrochemilluminescence. Data were shown as the average IL-6 expression or protein ± SEM. A paired student's t-test was used to determine significance; *, <i>P</i><0.05.</p
