scholarly journals The Aneugenicity of Ketone Bodies in Colon Epithelial Cells Is Mediated by Microtubule Hyperacetylation and Is Blocked by Resveratrol

2021 ◽  
Vol 22 (17) ◽  
pp. 9397
Author(s):  
Haruka Sudo ◽  
Akira Kubo
Keyword(s):  
Epithelial Cells ◽  
Ketone Bodies ◽  
Current Data ◽  
Colorectal Carcinogenesis ◽  
Fibroblast Cells ◽  
Oxygen Species ◽  
Histone Deacetylase 3 ◽  
Microtubule Severing ◽  
Diabetic Status ◽  
Increased Risk

Diabetes mellitus (DM) is considered to be associated with an increased risk of colorectal cancer. Recent studies have also revealed that tubulin hyperacetylation is caused by a diabetic status and we have reported previously that, under microtubule hyperacetylation, a microtubule severing protein, katanin-like (KL) 1, is upregulated and contributes to tumorigenesis. To further explore this phenomenon, we tested the effects of the ketone bodies, acetoacetate and β-hydroxybutyrate, in colon and fibroblast cells. Both induced microtubule hyperacetylation that responded differently to a histone deacetylase 3 knockdown. These two ketone bodies also generated intracellular reactive oxygen species (ROS) and hyperacetylation was commonly inhibited by ROS inhibitors. In a human fibroblast-based microtubule sensitivity test, only the KL1 human katanin family member showed activation by both ketone bodies. In primary cultured colon epithelial cells, these ketone bodies reduced the tau protein level and induced KL1- and α-tubulin acetyltransferase 1 (ATAT1)-dependent micronucleation. Resveratrol, known for its tumor preventive and tubulin deacetylation effects, inhibited this micronucleation. Our current data thus suggest that the microtubule hyperacetylation induced by ketone bodies may be a causal factor linking DM to colorectal carcinogenesis and may also represent an adverse effect of them that needs to be controlled if they are used as therapeutics.

Oxidative Stress Levels, JAK2V617F Mutational Status and Thrombotic Complications in Patients with Essential Thrombocythemia

2019 ◽  
Vol 70 (8) ◽  
pp. 2822-2825 ◽  
Author(s):  
Cornel Moisa ◽  
Mihnea Alexandru Gaman ◽  
Camelia Cristina Diaconu ◽  
Amelia Maria Gaman
Keyword(s):  
Oxidative Stress ◽  
Essential Thrombocythemia ◽  
Myeloproliferative Neoplasm ◽  
Oxygen Species ◽  
Mutational Status ◽  
Increased Risk ◽  
Stress Levels ◽  
Total Antioxidant ◽  
Thrombotic Complications ◽  
The Relationship

Essential thrombocythemia (ET) is a BCR-ABL1-negative myeloproliferative neoplasm associated with thrombotic and haemorrhagic complications. Reactive oxygen species (ROS) overexpression induces a growth advantage to JAK2V617F-positive clones and, in association with a higher number of immature platelets, leukocytosis, and additional cardiovascular risk factors, leads to an increased risk for thrombotic events. We evaluated oxidative stress by measuring ROS levels and the total antioxidant capacity (TAC) in 62 ET patients and investigated the relationship between oxidative stress, JAK2V617F mutational status and the development of thrombotic events. We found higher oxidative stress levels in JAK2V617F-positive vs. JAK2V617F-negative ET cases with no significant differences between homozygous and heterozygous genotypes. Increased ROS levels and thrombotic events were more frequent in ET patients with old age at diagnosis, higher haematocrit levels or leukocytosis.

Metabolic Complications and Kidney Transplantation: Focus on Glycaemia and Dyslipidaemia

2020 ◽  
Vol 18 (3) ◽  
pp. 273-281 ◽  
Author(s):  
Panagiotis Anagnostis ◽  
Stavroula Α. Paschou ◽  
Eleftherios Spartalis ◽  
Gerardo Sarno ◽  
Paride De Rosa ◽  
...  
Keyword(s):  
Graft Function ◽  
Current Data ◽  
Optimal Management ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Cvd Risk ◽  
Oral Hypoglycaemic Agents ◽  
Metabolic Complications ◽  
Increased Risk ◽  
Regimen Modification

Post-transplant diabetes mellitus (PTDM) and dyslipidaemia are the most common metabolic complications in kidney transplant recipients (KTR). They are associated with a higher risk of lower graft function and survival, as well as an increased risk of cardiovascular disease (CVD). The aim of this review is to provide current data on the epidemiology, pathophysiology and optimal management of these two principal metabolic complications in KTR. Several risk factors in this metabolic milieu are either already present or emerge after renal transplantation, such as those due to immunosuppressive therapy. However, the exact pathogenic mechanisms have not been fully elucidated. Awareness of these disorders is crucial to estimate CVD risk in KTR and optimize screening and therapeutic strategies. These include lifestyle (preferably according to the Mediterranean pattern) and immunosuppressive regimen modification, as well as the best available anti-diabetic (insulin or oral hypoglycaemic agents) and hypolipidaemic (e.g. statins) regimen according to an individual’s metabolic profile and medical history.

scholarly journals Surgical treatment of recalcitrant gastroesophageal reflux disease in patients with systemic sclerosis: a systematic review

2021 ◽  
Author(s):  
Alberto Aiolfi ◽  
Mario Nosotti ◽  
Kazuhide Matsushima ◽  
Carolina Perali ◽  
Cristina Ogliari ◽  
...  
Keyword(s):  
Systematic Review ◽  
Systemic Sclerosis ◽  
Surgical Treatment ◽  
Gastroesophageal Reflux Disease ◽  
Gastroesophageal Reflux ◽  
Reflux Disease ◽  
Current Data ◽  
Current Evidence ◽  
Increased Risk

Abstract Introduction Gastroesophageal reflux disease (GERD) is frequently seen in patients with systemic sclerosis (SSc). Long-standing GERD may cause esophagitis, long-segment strictures, and Barrett’s esophagus and may worsen pre-existing pulmonary fibrosis with an increased risk of end-stage lung disease. Surgical treatment of recalcitrant GERD remains controversial. The purpose of this systematic review was to summarize the current data on surgical treatment of recalcitrant GERD in SSc patients. Materials and methods A systematic literature review according to PRISMA and MOOSE guidelines. PubMed, EMBASE, and Web of Science databases were consulted. Results A total of 101 patients were included from 7 studies. The age ranged from 34 to 61 years and the majority were females (73.5%). Commonly reported symptoms were heartburn (92%), regurgitation (77%), and dysphagia (74%). Concurrent pulmonary disease was diagnosed in 58% of patients. Overall, 63 patients (62.4%) underwent open fundoplication, 17 (16.8%) laparoscopic fundoplication, 15 (14.9%) Roux en-Y gastric bypass (RYGB), and 6 (5.9%) esophagectomy. The postoperative follow-up ranged from 12 to 65 months. Recurrent symptoms were described in up to 70% and 30% of patients undergoing fundoplication and RYGB, respectively. Various symptoms were reported postoperatively depending on the type of surgical procedures, anatomy of the valve, need for esophageal lengthening, and follow-up. Conclusions The treatment of recalcitrant GERD in SSc patients is challenging. Esophagectomy should be reserved to selected patients. Minimally invasive RYGB appears feasible and safe with promising preliminary short-term results. Current evidence is scarce while a definitive indication about the most appropriate surgical treatment is lacking.

Cellular Samurai: katanin and the severing of microtubules

2000 ◽  
Vol 113 (16) ◽  
pp. 2821-2827 ◽  
Author(s):  
L. Quarmby
Keyword(s):  
Epithelial Cells ◽  
Essential Role ◽  
Aaa Atpase ◽  
C Elegans ◽  
Microtubule Severing ◽  
Biochemical Studies ◽  
New Evidence

Recent biochemical studies of the AAA ATPase, katanin, provide a foundation for understanding how microtubules might be severed along their length. These in vitro studies are complemented by a series of recent reports of direct in vivo observation of microtubule breakage, which indicate that the in vitro phenomenon of catalysed microtubule severing is likely to be physiological. There is also new evidence that microtubule severing by katanin is important for the production of non-centrosomal microtubules in cells such as neurons and epithelial cells. Although it has been difficult to establish the role of katanin in mitosis, new genetic evidence indicates that a katanin-like protein, MEI-1, plays an essential role in meiosis in C. elegans. Finally, new proteins involved in the severing of axonemal microtubules have been discovered in the deflagellation system of Chlamydomonas.

Localized activation of the metastatic phenotype within the perineural region in prostate cancer.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 253-253
Author(s):  
Mick D. Brown ◽  
Claire Alexandre Hart ◽  
Ashwin Sachdeva ◽  
Christian Faulkner ◽  
David Wedge ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Epithelial Cells ◽  
Pathological Finding ◽  
Clinical History ◽  
Metastatic Progression ◽  
Metastatic Phenotype ◽  
Increased Risk ◽  
Phenotypic Characterisation ◽  
Local Tumour ◽  
Tumour Lesion

253 Background: Perineural Invasion (PNI) is defined as malignant epithelial cell invasion of the perineural space and nerves. Despite widespread acknowledgement of the clinical significance of PNI as a PCa pathological finding associated with recurrence, increased risk of bone metastasis and poor survival, the molecular mechanism underlying this pathology is relatively unknown. The malignant epithelial cells within the PNI potentially provides a spatially defined “snapshot” of disease progression, as the cells switch to a more migrational phenotype associated with metastatic progression. Here we present the initial spatial PNI phenotypic characterisation in PCa. Methods: Archival FFPE blocks, with associated full clinical history, from patients who underwent a radical prostatectomy for prostate cancer were retrieved under research ethics REC#07/H1003/161+5 10_NOCL_02. Biomarkers EphA2, pEphA2s897, pMLC2, E-Cadherin, Vimentin, TOMM20, MTC01, NDUFB8, PTEN were assessed on 4µm serial sections stained using a multiplex TSA protocol, with S100, pan-cytokeratin and DAPI acting as landmarks, on a Ventana Discovery platform prior to scanning on a Versa 3 platform with Halo image analysis. Prostate zones were defined at 500µm intervals either side of the prostate capsule. Univariate and multivariate (hierarchical clustering, UMap clustering) expression analysis and correlation with clinic-pathological features was conducted within R. Results: The PNI epithelial cells within each spatial zone of the prostate are significantly different to each other (Kruskal-Wallis test p < 2.2x10−16 except for MTC01 p = 5.3x10−10). In comparison with the local tumour lesion, PNI epithelial cells localised within 1000µm of the prostate edge and outside the tumour lesion, have undergone a migrational switch, gaining features associated with an activated metastatic phenotype, with increased expression of amoeboid signalling (EphA2, pEphA2s897, pMLC2) and mitochondrial defects (loss of Complex I and IV, gain of mitochondrial mass (TOMM20)). Patients clustering by multivariate expression trends across the prostate regions showed 4 distinct patient groups, with PNI epithelial cells in patient group 1 & 2 displaying a more epithelial to mesenchymal (EMT) phenotype, especially in the first 1000µm inside the prostate organ. Conclusions: Cells within PNI close to the edge of the prostate have features consistent with a switch to migrational/metastatic activation in contrast to the more indolent cell type found deeper within the tumour. Further characterisation of this localised migrational upregulation will help in understanding the transition from a localised to a metastatic phenotype.

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