| 1. |
- Algaber, Anwar, et al.
(författare)
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MicroRNA-340-5p inhibits colon cancer cell migration via targeting of RhoA
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 16934-16934
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Tidskriftsartikel (refereegranskat)abstract
- Colon cancer is the third most common cancer and a significant cause of cancer-related deaths worldwide. Metastasis is the most insidious aspect of cancer progression. Convincing data suggest that microRNAs (miRs) play a key function in colon cancer biology. We examined the role of miR-340-5p in regulating RhoA expression as well as cell migration and invasion in colon cancer cells. Levels of miR-340-5p and RhoA mRNA varied inversely in serum-free and serum-grown HT-29 and AZ-97 colon cancer cells. It was found transfection with miR-340-5p not only decreased expression of RhoA mRNA and protein levels in HT-29 cells but also reduced colon cancer cell migration and invasion. Bioinformatics analysis predicted one putative binding sites at the 3'-UTR of RhoA mRNA. Targeting this binding site with a specific blocker reversed mimic miR-340-5p-induced inhibition of RhoA activation and colon cancer cell migration and invasion. These novel results suggest that miR-340-5p is an important regulator of colon cancer cell motility via targeting of RhoA and further experiments are warranted to evaluate the role of miR-340-5p in colon cancer metastasis.
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| 2. |
- Aurin, Johanna, et al.
(författare)
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Age at first childbirth and breast cancer survival : A prospective cohort study
- 2020
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Ingår i: BMC Research Notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Late age at first childbirth is a well-established risk factor for breast cancer. Previous studies have, however, shown conflicting results to whether late age at first childbirth also influences the prognosis of breast cancer survival. The aim of this study was to examine age at first birth in relation to survival after breast cancer diagnosis. Results: We used information from the Malmö Diet and Cancer study. At baseline 17,035 women were included. All women were followed from the year they developed breast cancer until they either died or until the end of follow-up. All women were asked how many children they had given birth to and were then divided into different groups, ≤ 20, > 20 to ≤ 25, > 25 to ≤ 30 and > 30. Nulliparous women form a separate group. Survival analyses were then performed using Cox proportional hazard survival analysis. Women in all age groups had a lower risk of breast cancer specific death as compared to the reference group ≤ 20, however non-significantly. Nulliparous women had a higher risk of breast cancer specific death as compared to the same reference group, however these results were not statistically significant. We could not see any negative effect of late first childbirth on breast cancer specific survival.
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| 3. |
- Ciuti, Gastone, et al.
(författare)
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Frontiers of robotic colonoscopy : A comprehensive review of robotic colonoscopes and technologies
- 2020
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Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 9:6
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Forskningsöversikt (refereegranskat)abstract
- Flexible colonoscopy remains the prime mean of screening for colorectal cancer (CRC) and the gold standard of all population-based screening pathways around the world. Almost 60% of CRC deaths could be prevented with screening. However, colonoscopy attendance rates are affected by discomfort, fear of pain and embarrassment or loss of control during the procedure. Moreover, the emergence and global thread of new communicable diseases might seriously affect the functioning of contemporary centres performing gastrointestinal endoscopy. Innovative solutions are needed: artificial intelligence (AI) and physical robotics will drastically contribute for the future of the healthcare services. The translation of robotic technologies from traditional surgery to minimally invasive endoscopic interventions is an emerging field, mainly challenged by the tough requirements for miniaturization. Pioneering approaches for robotic colonoscopy have been reported in the nineties, with the appearance of inchworm-like devices. Since then, robotic colonoscopes with assistive functionalities have become commercially available. Research prototypes promise enhanced accessibility and flexibility for future therapeutic interventions, even via autonomous or robotic-assisted agents, such as robotic capsules. Furthermore, the pairing of such endoscopic systems with AI-enabled image analysis and recognition methods promises enhanced diagnostic yield. By assembling a multidisciplinary team of engineers and endoscopists, the paper aims to provide a contemporary and highly-pictorial critical review for robotic colonoscopes, hence providing clinicians and researchers with a glimpse of the major changes and challenges that lie ahead.
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| 4. |
- Linders, Johan, et al.
(författare)
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Extracellular cold-inducible RNA-binding protein regulates neutrophil extracellular trap formation and tissue damage in acute pancreatitis
- 2020
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Ingår i: Laboratory Investigation. - : Elsevier BV. - 0023-6837. ; 100:12, s. 1618-1630
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Tidskriftsartikel (refereegranskat)abstract
- Neutrophil extracellular traps (NETs) play a key role in the development of acute pancreatitis (AP). In the present study, we studied the role of extracellular cold-inducible RNA-binding protein (eCIRP), a novel damage-associated-molecular-pattern molecule, in severe AP. C57BL/6 mice underwent retrograde infusion of taurocholate into the pancreatic duct. C23, an eCIRP inhibitor, was given 1 h prior to induction of AP. Pancreatic, lung, and blood samples were collected and levels of citrullinated histone 3, DNA-histone complexes, eCIRP, myeloperoxidase (MPO), amylase, cytokines, matrix metalloproteinase-9 (MMP-9), and CXC chemokines were quantified after 24 h. NETs were detected by electron microscopy in the pancreas and bone marrow-derived neutrophils. Amylase secretion was analyzed in isolated acinar cells. Plasma was obtained from healthy individuals and patients with mild and moderate severe or severe AP. Taurocholate infusion induced NET formation, inflammation, and tissue injury in the pancreas. Pretreatment with C23 decreased taurocholate-induced pancreatic and plasma levels of eCIRP and tissue damage in the pancreas. Blocking eCIRP reduced levels of citrullinated histone 3 and NET formation in the pancreas as well as DNA-histone complexes in the plasma. In addition, administration of C23 attenuated MPO levels in the pancreas and lung of mice exposed to taurocholate. Inhibition of eCIRP reduced pancreatic levels of CXC chemokines and plasma levels of IL-6, HMGB-1, and MMP-9 in mice with severe AP. Moreover, eCIRP was found to be bound to NETs. Coincubation with C23 reduced NET-induced amylase secretion in isolated acinar cells. Patients with severe AP had elevated plasma levels of eCIRP compared with controls. Our novel findings suggest that eCIRP is a potent regulator of NET formation in the inflamed pancreas. Moreover, these results show that targeting eCIRP with C23 inhibits inflammation and tissue damage in AP. Thus, eCIRP could serve as an effective target to attenuate pancreatic damage in patients with AP.
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| 5. |
- Verma, Vivek, et al.
(författare)
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α-Hemolysin of uropathogenic E. coli regulates NLRP3 inflammasome activation and mitochondrial dysfunction in THP-1 macrophages
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Hemolysin expressing UPEC strains have been associated with severe advanced kidney pathologies, such as cystitis and pyelonephritis, which are associated with an inflammatory response. Macrophages play an important role in regulating an inflammatory response during a urinary tract infection. We have studied the role of purified recombinant α-hemolysin in inducing inflammatory responses and cell death in macrophages. Acylation at lysine residues through HlyC is known to activate proHlyA into a fully functional pore-forming toxin, HlyA. It was observed that active α-hemolysin (HlyA) induced cleavage of caspase-1 leading to the maturation of IL-1β, while inactive α-hemolysin (proHlyA) failed to do so in THP-1 derived macrophages. HlyA also promotes deubiquitination, oligomerization, and activation of the NLRP3 inflammasome, which was found to be dependent on potassium efflux. We have also observed the co-localization of NLRP3 within mitochondria during HlyA stimulations. Moreover, blocking of potassium efflux improved the mitochondrial health in addition to a decreased inflammatory response. Our study demonstrates that HlyA stimulation caused perturbance in potassium homeostasis, which led to the mitochondrial dysfunction followed by an acute inflammatory response, resulting in cell death. However, the repletion of intracellular potassium stores could avoid HlyA induced macrophage cell death. The findings of this study will help to understand the mechanism of α-hemolysin induced inflammatory response and cell death.
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| 6. |
- Winsnes, Annika
(författare)
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Evaluating an experimental model consecutive to abdominal wall hernia repair outcome
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Abdominal wall hernia is a common surgically treated condition. Patients with primary umbilical hernia are operated with suture or mesh repair, but recurrence and complication rates have been debated.Larger abdominal wall hernias need implantation of reinforcing material for repair. Synthetic implants are dominating. In complex hernia cases neither synthetic nor biologic implants are optimal. A randomized controlled trial has revealed satisfactory results from autologous full thickness skin grafts (FTSGs) in onlay position. Further application intraperitoneally (IPOM) in laparoscopic surgery and for repair of parastomal hernia in humans, must be based on a translational concept including animal and morphologic studies since the IPOM position has not been evaluated systematically. This thesis aims to be a link in a translational chain, focused on establishing an experimental model for FTSG evaluation.Problem formulations: - Does synthetic mesh decrease the probability of recurrence and/or complications in primary umbilical hernia?- Can FTSG be evaluated for IPOM versus onlay position in a transgenic mouse model using luminescence from substrate activated by the enzyme luciferase expressed in donor tissue?- How does the FTSG in IPOM position perform compared to FTSG in onlay position?Results:Recurrence rate at a median of 6.8 years follow-up was 9% for suture- and 8% for mesh repair, odds ratio (OR) 0.9, 95% confidence interval (CI) 0.40-2.02, in 306 patients investigated patients. Surgical complications were in favor of suture repair, OR 6.6, 95% CI 2.29-20.38.In an experimental evaluation of FTSG, 20 mice received intervention with either onlay or IPOM graft. Survival of FTSG was revealed for 8 weeks by luminescence detection. All animals regained weight within 8 days in median. At sacrifice 8 weeks postoperatively, adhesions were evaluated by a modified Jenkins’ scale. No onlay mice displayed adhesions while two IPOM mice had firm and one dense adhesions. Inflammatory response evaluated in four animals expressing nuclear factor ĸB (NF-ĸB) showed a peak at day 2 and returned to stable low levels from day 5 until end of the 33-day follow up. FTSG in IPOM position showed similar morphology and immunohistochemistry stain patterns as controls in onlay position. There was a low expression of the inflammatory markers tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and myeloperoxidase. Vascular structures were visualized by von Willebrand factor-stain. In Picrosirius red stain, collagen bundles in dermis of FTSG in both IPOM and onlay position was thicker, compared to internal controls. FTSG extracellular matrix had metamorphosed mainly into thick collagen bundles, with partially degraded skin appendages. Matrix metalloproteinases (MMP)-stain from MMP-1, MMP-8 and MMP-9 were not co-distributed with their respective collagen substrates.Conclusions:Synthetic mesh does not decrease the probability of recurrence but significantly increase complications in repair of small umbilical hernia. FTSG can be evaluated in IPOM and onlay position in an experimental transgenic mouse model. The two positions were similar in terms of graft survival, few adhesions, micro-vessel formation, low grade inflammation, cyst formation and collagen distribution. FTSG implanted in IPOM position does not exhibit any systematic differences from onlay position, thus from this perspective no difference in biomechanical behavior can be anticipated.
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