| 1. |
- Chen, Ying, et al.
(författare)
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Enhanced colonic tumorigenesis in alkaline sphingomyelinase (NPP7) knockout mice.
- 2015
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Ingår i: Molecular Cancer Therapeutics. - 1538-8514. ; 14:1, s. 259-267
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Tidskriftsartikel (refereegranskat)abstract
- Intestinal alkaline sphingomyelinase (alk-SMase) generates ceramide and inactivates platelet-activating factor (PAF) and is previously suggested to have anticancer properties. The direct evidence is still lacking. We studied colonic tumorigenesis in alk-SMase knockout (KO) mice. Formation of aberrant crypt foci (ACF) was examined after azoxymethane (AOM) injection. Tumor was induced by AOM alone, a conventional AOM/dextran sulfate sodium (DSS) treatment, and an enhanced AOM/DSS method. beta-catenin was determined by immunohistochemistry, PAF levels by ELISA and sphingomyelin metabolites by mass spectrometry. Without treatment, spontaneous tumorigenesis was not identified but the intestinal mucosa appeared thicker in KO than in wild type (WT) littermates. AOM alone induced more ACF in KO mice but no tumors 28 weeks after injection. However, combination of AOM/DSS treatments induced colonic tumors and the incidence was significantly higher in KO than in WT mice. By the enhanced AOM/DSS method tumor number per mouse increased 4.5 times and tumor size 1.8 times in KO compared to WT mice. While all tumors were adenomas in WT mice, 32% were adenocarcinomas in KO mice. Compared to WT mice, cytosol expression of beta-catenin was significantly decreased and nuclear translocation in tumors was more pronounced in KO mice. Lipid analysis showed decreased ceramide in small intestine and increased sphingosine-1-phosphate in both small intestine and colon in nontreated KO mice. PAF levels in feces were significantly higher in the KO mice after AOM/DSS treatment. In conclusion lack of alk-SMase markedly increases AOM/DSS induced colonic tumorigenesis associated with decreased ceramide and increased sphingosine-1-phosphate and PAF levels.
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| 2. |
- Cheng, Xiaowen, et al.
(författare)
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A novel serotonin-containing tuft cell subpopulation in mouse intestine
- 2019
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Ingår i: Cell and Tissue Research. - : Springer Science and Business Media LLC. - 0302-766X .- 1432-0878. ; 376:2, s. 189-197
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Tidskriftsartikel (refereegranskat)abstract
- In this study, a novel subset of doublecortin-like kinase 1 (DCLK1)-immunoreactive (IR) tuft cells that also contain serotonin (5-hydroxytryptamine, 5HT) is described, in terms of their number, regional distribution, possible synthesis or reuptake of 5HT and proximity to 5-HT-containing enterochromaffin (EC) cells. The small intestine from C57BL/6J mice was divided into five segments while the large intestine was kept undivided. Double immunostaining was used to estimate numbers and topographic distribution of 5HT-IR (DCLK1/5HT) tuft cells and their possible expression of tryptophan hydroxylase (TPH) and serotonin transporter (SERT). Also, possible contacts between tuft cells and 5HT-IR EC cells were studied. In the small intestine, up to 80% of all tuft cells were identified as DCLK1/5HT-IR; in the large intestine, such cells were rare. The highest number of DCLK1/5HT-IR cells was found in the upper small intestine. The numbers of DCLK1/5HT-IR cells gradually decreased distally. DCLK1-IR tuft cells were not found to contain TPH, the rate-limiting enzyme in 5HT synthesis. SERT, the selective transporter for 5HT reuptake, could not convincingly be demonstrated in tuft cells. In villi and crypts, 3% and 10%, respectively, of all DCLK1-IR cells were in close proximity to EC cells. EC cells in close proximity to DCLK1-IR cells were, in villi and crypts, 3 and 8%, respectively. We conclude that DCLK1/5HT-IR cells constitute a novel subset of tuft cells that may have unique roles in the GI tract.
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| 3. |
- Cheng, Xiaowen, et al.
(författare)
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Focal, but not global, cerebral ischaemia causes loss of myenteric neurons and upregulation of vasoactive intestinal peptide in mouse ileum
- 2018
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Ingår i: International Journal of Experimental Pathology. - : Wiley. - 0959-9673. ; 99:1, s. 38-45
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Tidskriftsartikel (refereegranskat)abstract
- Reduced blood flow to the brain induces cerebral ischaemia, potentially causing central injury and peripheral complications including gastrointestinal (GI) dysfunction. The pathophysiology behind GI symptoms is suspected to be neuropathy in the enteric nervous system (ENS), which is essential in regulating GI function. This study investigates if enteric neuropathy occurs after cerebral ischaemia, by analysing neuronal survival and relative numbers of vasoactive intestinal peptide (VIP) and neuronal nitric oxide synthase (nNOS) expressing neurons in mouse ileum after three types of cerebral ischaemia. Focal cerebral ischaemia, modelled by permanent middle cerebral artery occlusion (pMCAO) and global cerebral ischaemia, modelled with either transient occlusion of both common carotid arteries followed by reperfusion (GCIR) or chronic cerebral hypoperfusion (CCH) was performed on C56BL/6 mice. Sham-operated mice for each ischaemia model served as control. Ileum was collected after 1–17 weeks, depending on model, and analysed using morphometry and immunocytochemistry. For each group, intestinal mucosa and muscle layer thicknesses, neuronal numbers and relative proportions of neurons immunoreactive (IR) for nNOS or VIP were estimated. No alterations in mucosa or muscle layer thicknesses were noted in any of the groups. Loss of myenteric neurons and an increased number of VIP-IR submucous neurons were found in mouse ileum 7 days after pMCAO. None of the global ischaemia models showed any alterations in neuronal survival or relative numbers of VIP- and nNOS-IR neurons. We conclude that focal cerebral ischaemia and global cerebral ischaemia influence enteric neuronal survival differently. This is suggested to reflect differences in peripheral neuro-immune responses.
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| 4. |
- Cheng, Xiaowen, et al.
(författare)
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Galectin-3 causes enteric neuronal loss in mice after left sided permanent middle cerebral artery occlusion, a model of stroke
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- In addition to brain injury stroke patients often suffer gastrointestinal complications. Neuroimmune interactions involving galectin-3, released from microglia in the brain, mediates the post-stroke pro-inflammatory response. We investigated possible consequences of stroke on the enteric nervous system and the involvement of galectin-3. We show that permanent middle cerebral artery occlusion (pMCAO) induces loss of enteric neurons in ileum and colon in galectin-3 +/+, but not in galectin-3 mice. In vitro we show that serum from galectin-3 +/+, but not from galectin-3 mice subjected to pMCAO, caused loss of C57BL/6J myenteric neurons, while myenteric neurons derived from TLR4 mice were unaffected. Further purified galectin-3 (10 6 M) caused loss of cultured C57BL/6J myenteric neurons. Inhibitors of transforming growth factor β-activated kinase 1 (TAK1) or AMP activated kinase (AMPK) counteracted both the purified galectin-3 and the galectin-3 +/+ pMCAO serum-induced loss in vitro. Combined we show that stroke (pMCAO) triggers central and peripheral galectin-3 release causing enteric neuronal loss through a TLR4 mediated mechanism involving TAK1 and AMPK. Galectin-3 is suggested a target for treatment of post-stroke complications.
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| 5. |
- Cheng, Xiaowen, et al.
(författare)
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Tuft cells : Distribution and connections with nerves and endocrine cells in mouse intestine
- 2018
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Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827. ; 369:1, s. 105-111
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Tidskriftsartikel (refereegranskat)abstract
- Tuft cells are gastrointestinal (GI) sensory cells recognized by their characteristic shape and their microvilli “tuft”. Aims of the present study were to elucidate their regional distribution and spatial connections with satiety associated endocrine cells and nerve fibers throughout the intestinal tract. C57BL/6 J mice were used in the experiments. The small intestine was divided into five segments, and the large intestine was kept undivided. The segments were coiled into “Swiss rolls”. Numbers and topographic distribution of tuft cells and possible contacts with endocrine cells and nerve fibers were estimated in the different segments, using immunocytochemistry. Tuft cells were found throughout the intestines; the highest number was in proximal small intestine. Five percent of tuft cells were found in close proximity to cholecystokinin-immunoreactive (IR) endocrine cells and up to 10% were in contact with peptide YY- and glucagon-like peptide-1-IR endocrine cells. Sixty percent of tuft cells in the small intestine and 40% in the large intestine were found in contact with nerve fibers. Calcitonin gene-related peptide-IR fibers constituted one-third of the fiber-contacts in the small intestine and two-thirds in the large intestine. These observations highlight the possibility of tuft cells as modulators of GI activities in response to luminal signaling.
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| 6. |
- Ekblad, Lars, et al.
(författare)
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Anti- or pro-proliferation - Conditional options for TGF-α and cetuximab in head and neck squamous cell carcinoma.
- 2015
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Ingår i: Oral Oncology. - : Elsevier BV. - 1879-0593 .- 1368-8375. ; 51:1, s. 46-52
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Tidskriftsartikel (refereegranskat)abstract
- Cetuximab is an epidermal growth factor receptor (EGFR)-targeting drug that has shown effects in head and neck squamous cell carcinoma (HNSCC). The effects are, however, small and have mainly been proven in a subset of patients, and the cost-effectiveness has been questioned. For this reason, we need to know more about the basic mechanisms controlling the effect of EGFR signalling on tumour growth.
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| 7. |
- Jolayemi, Okanlawon Lekan, et al.
(författare)
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Fysiologisk utveckling hos den unga sockerbetan - växtbaserade protein som en biostimulant
- 2019
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Ingår i: LTV-fakultetens faktablad.
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Annan publikation (populärvet., debatt m.m.)abstract
- Växtbaserade proteiner från potatis och vete kan användas som biostimulanter vid odling av unga sockerbetor. Tillväxten hos sockerbetorna ökar vid en låg tillsats av dessa biostimulanter. Den fysiologiska förklaringen till denna ökning är idag oklar och behöver utredas vidare. En tidig utveckling och etablering av tillväxten hos sockerbetan kan ha en inverkan på den slutgiltiga avkastningen (rot- och sockeravkastning) hos sockerbetan.
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| 8. |
- Jönsson, Anette, et al.
(författare)
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Long‑term follow‑up of buserelin‑induced enteric neuropathy in rats.
- 2016
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-3004 .- 1791-2997. ; 13:4, s. 3507-3513
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Tidskriftsartikel (refereegranskat)abstract
- A few patients have been shown to develop severe abdominal pain and gastrointestinal dysmotility during treatment with gonadotropin‑releasing hormone (GnRH) analogs. A rat model of enteric neuropathy has been developed by administration of the GnRH analog buserelin to rats. Loss of enteric neurons and ganglioneuritis throughout the gastrointestinal tract has been described, without other histopathological changes. The aim of the present study was to investigate the long‑term effects of this rat model on body weight, and on morphology and inflammatory changes in the gastrointestinal tract. Rats were administered subcutaneous injections of buserelin or saline once daily for 5 days and allowed to recover for 3 weeks. This regimen was repeated four times. The rats were weighed weekly and were sacrificed 16 weeks after the fourth treatment. The bowel wall was measured by morphometry, and the presence of enteric neurons, mast cells, eosinophils and T‑lymphocytes was evaluated. Buserelin‑treated rats were shown to have a lower body weight at sacrifice, as compared with the controls (P<0.05). Compared with controls, buserelin treatment caused loss of myenteric neurons in the ileum and colon (P<0.01), a thinner circular muscle layer in ileum (P<0.05) and longitudinal muscle layer in colon (P<0.05), increased number of eosinophils in the submucosa of the ileum (P<0.05), and an increased number of T‑lymphocytes in the submucosa and circular muscle layer of the fundus (P<0.01 and P<0.05, respectively) and circular muscle layer of the colon (P<0.05). Mast cells were equally distributed in the two groups. Thus, long‑term follow‑up of buserelin‑induced enteric neuropathy reveals reduced body weight, loss of myenteric neurons, thinning of muscle layers, and increased numbers of eosinophils and T‑lymphocytes in the gastrointestinal tract.
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| 9. |
- Mccourt, Andy, et al.
(författare)
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Characterization of Gastric Mucosa Biopsies Reveals Alterations in Huntington's Disease.
- 2015
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Ingår i: PLoS Currents. - : Public Library of Science (PLoS). - 2157-3999. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Weight loss is an important complication of Huntington's disease (HD), however the mechanism for weight loss in HD is not entirely understood. Mutant huntingtin is expressed in the gastrointestinal (GI) tract and, in HD mice, mutant huntingtin inclusions are found within the enteric nervous system along the GI tract. A reduction of neuropeptides, decreased mucosal thickness and villus length, as well as gut motility impairment, have also been shown in HD mice. We therefore set out to study gastric mucosa of patients with HD, looking for abnormalities of mucosal cells using immunohistochemistry. In order to investigate possible histological differences related to gastric acid production, we evaluated the cell density of acid producing parietal cells, as well as gastrin producing cells (the endocrine cell controlling parietal cell function). In addition, we looked at chief cells and somatostatin-containing cells. In gastric mucosa from HD subjects, compared to control subject biopsies, a reduced expression of gastrin (a marker of G cells) was found. This is in line with previous HD mouse studies showing reduction of GI tract neuropeptides.
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| 10. |
- Olsson, Jan-Eric, et al.
(författare)
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Psychometric analysis of the Swedish version of the General Medical Council's multi source feedback questionnaires
- 2017
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Ingår i: International Journal of Medical Education. - : International Journal of Medical Education. - 2042-6372. ; 8, s. 252-261
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To determine the internal consistency and the underlying components of our translated and adapted Swedish version of the General Medical Council's multisource feedback questionnaires (GMC questionnaires) for physicians and to confirm which aspects of good medical practice the latent variable structure reflected.Methods: From October 2015 to March 2016, residents in family medicine in Sweden were invited to participate in the study and to use the Swedish version to perform self-evaluations and acquire feedback from both their patients and colleagues. The validation focused on internal consistency and construct validity. Main outcome measures were Cronbach’s alpha coefficients, Principal Component Analysis, and Confirmatory Factor Analysis indices.Results: A total of 752 completed questionnaires from patients, colleagues, and residents were analysed. Of these, 213 comprised resident self-evaluations, 336 were feedback from residents’ patients, and 203 were feedback from residents’ colleagues. Cronbach’s alpha coefficients of the scores were 0.88 from patients, 0.93 from colleagues, and 0.84 in the self-evaluations. The Confirmatory Factor Analysis validated two models that fit the data reasonably well and reflected important aspects of good medical practice. The first model had two latent factors for patient-related items concerning empathy and consultation management, and the second model had five latent factors for colleague-related items, including knowledge and skills, attitude and approach, reflection and development, teaching, and trust.Conclusions: The current Swedish version seems to be a reliable and valid tool for formative assessment for resident physicians and their supervisors. This needs to be verified in larger samples.
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