| 1. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 6. |
- Zaborowski, AM, et al.
(författare)
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Microsatellite instability in young patients with rectal cancer: molecular findings and treatment response
- 2022
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Ingår i: The British journal of surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 109:3, s. 251-255
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Tidskriftsartikel (refereegranskat)abstract
- In this study of 400 patients with early-onset rectal cancer, 12.5 per cent demonstrated microsatellite instability (MSI). MSI was associated with a reduced likelihood of nodal positivity, an increased rate of pathological complete response, and improved disease-specific survival.
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| 10. |
- Carmona-Gutierrez, D, et al.
(författare)
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The flavonoid 4,4'-dimethoxychalcone promotes autophagy-dependent longevity across species
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 651-
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Tidskriftsartikel (refereegranskat)abstract
- Ageing constitutes the most important risk factor for all major chronic ailments, including malignant, cardiovascular and neurodegenerative diseases. However, behavioural and pharmacological interventions with feasible potential to promote health upon ageing remain rare. Here we report the identification of the flavonoid 4,4′-dimethoxychalcone (DMC) as a natural compound with anti-ageing properties. External DMC administration extends the lifespan of yeast, worms and flies, decelerates senescence of human cell cultures, and protects mice from prolonged myocardial ischaemia. Concomitantly, DMC induces autophagy, which is essential for its cytoprotective effects from yeast to mice. This pro-autophagic response induces a conserved systemic change in metabolism, operates independently of TORC1 signalling and depends on specific GATA transcription factors. Notably, we identify DMC in the plant Angelica keiskei koidzumi, to which longevity- and health-promoting effects are ascribed in Asian traditional medicine. In summary, we have identified and mechanistically characterised the conserved longevity-promoting effects of a natural anti-ageing drug.
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| 14. |
- Castoldi, F, et al.
(författare)
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Autophagy-mediated metabolic effects of aspirin
- 2020
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Ingår i: Cell death discovery. - : Springer Science and Business Media LLC. - 2058-7716. ; 6:1, s. 129-
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Tidskriftsartikel (refereegranskat)abstract
- Salicylate, the active derivative of aspirin (acetylsalicylate), recapitulates the mode of action of caloric restriction inasmuch as it stimulates autophagy through the inhibition of the acetyltransferase activity of EP300. Here, we directly compared the metabolic effects of aspirin medication with those elicited by 48 h fasting in mice, revealing convergent alterations in the plasma and the heart metabolome. Aspirin caused a transient reduction of general protein acetylation in blood leukocytes, accompanied by the induction of autophagy. However, these effects on global protein acetylation could not be attributed to the mere inhibition of EP300, as determined by epistatic experiments and exploration of the acetyl-proteome from salicylate-treated EP300-deficient cells. Aspirin reduced high-fat diet-induced obesity, diabetes, and hepatosteatosis. These aspirin effects were observed in autophagy-competent mice but not in two different models of genetic (Atg4b−/− or Bcln1+/−) autophagy-deficiency. Aspirin also improved tumor control by immunogenic chemotherapeutics, and this effect was lost in T cell-deficient mice, as well as upon knockdown of an essential autophagy gene (Atg5) in cancer cells. Hence, the health-improving effects of aspirin depend on autophagy.
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| 21. |
- Frontali, A., et al.
(författare)
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Segmental Colectomy for Ulcerative Colitis: Is There a Place in Selected Patients Without Active Colitis? An International Multicentric Retrospective Study in 72 Patients
- 2020
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Ingår i: Journal of Crohn's & Colitis. - : OXFORD UNIV PRESS. - 1873-9946 .- 1876-4479. ; 14:12, s. 1687-1692
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: The aim of this study was to report a multicentric experience of segmental colectomy [SC] in ulcerative colitis [UC] patients without active colitis, in order to assess if SC can or cannot represent an alternative to ileal pouch-anal anastomosis [IPAA]. Methods: All UC patients undergoing SC were included. Postoperative complications according to Clavien-Dindos classification, long-term results, and risk factors for postoperative colitis and reoperation for colitis on the remnant colon, were assessed. Results: A total of 72 UC patients underwent: sigmoidectomy [n = 28], right colectomy [n = 24], proctectomy [n = 11], or left colectomy [n = 9] for colonic cancer [n = 27], diverticulitis [n = 17], colonic stenosis [n = 5], dysplasia or polyps [n = 8], and miscellaneous [n = 15]. Three patients died postoperatively and 5/69 patients [7%] developed early flare of UC within 3 months after SC. After a median follow-up of 40 months, 24/ 69 patients [35%] were reoperated after a median delay after SC of 19 months [range, 2-158 months]: 22/24 [92%] underwent total colectomy and ileorectal anastomosis [n = 9] or total coloproctectomy [TCP] [n = 13] and 2/24 [8%] an additional SC. Reasons for reoperation were: colitis [n = 14; 20%], cancer [n = 3] or dysplasia [n = 3], colonic stenosis [n = 1], and unknown reasons [n = 3]. Endoscopic score of colitis before SC was Mayo 23 in 5/5 [100%] patients with early flare vs 15/42 without early flare [36%; p = 0.0101] and in 9/12 [75%] patients with reoperation for colitis vs 11/35 without reoperation [31%; p = 0.016]. Conclusions: After segmental colectomy in UC patients, postoperative early colitis is rare [7%]. Segmental colectomy could possibly represent an alternative to IPAA in selected UC patients without active colitis.
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| 22. |
- Joseph, A, et al.
(författare)
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Metabolic and psychiatric effects of acyl coenzyme A binding protein (ACBP)/diazepam binding inhibitor (DBI)
- 2020
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Ingår i: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 11:7, s. 502-
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Tidskriftsartikel (refereegranskat)abstract
- Acyl coenzyme A binding protein (ACBP), also known as diazepam binding inhibitor (DBI) is a multifunctional protein with an intracellular action (as ACBP), as well as with an extracellular role (as DBI). The plasma levels of soluble ACBP/DBI are elevated in human obesity and reduced in anorexia nervosa. Accumulating evidence indicates that genetic or antibody-mediated neutralization of ACBP/DBI has anorexigenic effects, thus inhibiting food intake and inducing lipo-catabolic reactions in mice. A number of anorexiants have been withdrawn from clinical development because of their side effects including an increase in depression and suicide. For this reason, we investigated the psychiatric impact of ACBP/DBI in mouse models and patient cohorts. Intravenously (i.v.) injected ACBP/DBI protein conserved its orexigenic function when the protein was mutated to abolish acyl coenzyme A binding, but lost its appetite-stimulatory effect in mice bearing a mutation in the γ2 subunit of the γ-aminobutyric acid (GABA) A receptor (GABAAR). ACBP/DBI neutralization by intraperitoneal (i.p.) injection of a specific mAb blunted excessive food intake in starved and leptin-deficient mice, but not in ghrelin-treated animals. Neither i.v. nor i.p. injected anti-ACBP/DBI antibody affected the behavior of mice in the dark–light box and open-field test. In contrast, ACBP/DBI increased immobility in the forced swim test, while anti-ACBP/DBI antibody counteracted this sign of depression. In patients diagnosed with therapy-resistant bipolar disorder or schizophrenia, ACBP/DBI similarly correlated with body mass index (BMI), not with the psychiatric diagnosis. Patients with high levels of ACBP/DBI were at risk of dyslipidemia and this effect was independent from BMI, as indicated by multivariate analysis. In summary, it appears that ACBP/DBI neutralization has no negative impact on mood and that human depression is not associated with alterations in ACBP/DBI concentrations.
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