scholarly journals Mitochondrial Respiration in KRAS and BRAF Mutated Colorectal Tumors and Polyps

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 815 ◽  
Author(s):  
Egle Rebane-Klemm ◽  
Laura Truu ◽  
Leenu Reinsalu ◽  
Marju Puurand ◽  
Igor Shevchuk ◽  
...  
Keyword(s):  
Mitochondrial Respiration ◽  
Atp Synthesis ◽  
Colorectal Polyps ◽  
Metabolic Phenotype ◽  
Mitochondrial Outer Membrane ◽  
Control Group ◽  
Colon Polyps ◽  
Wild Type ◽  
Tissue Samples ◽  
Potential Component

This study aimed to characterize the ATP-synthesis by oxidative phosphorylation in colorectal cancer (CRC) and premalignant colon polyps in relation to molecular biomarkers KRAS and BRAF. This prospective study included 48 patients. Resected colorectal polyps and postoperative CRC tissue with adjacent normal tissue (control) were collected. Patients with polyps and CRC were divided into three molecular groups: KRAS mutated, BRAF mutated and KRAS/BRAF wild-type. Mitochondrial respiration in permeabilized tissue samples was observed using high resolution respirometry. ADP-activated respiration rate (Vmax) and an apparent affinity of mitochondria to ADP, which is related to mitochondrial outer membrane (MOM) permeability, were determined. Clear differences were present between molecular groups. KRAS mutated CRC group had lower Vmax values compared to wild-type; however, the Vmax value was higher than in the control group, while MOM permeability did not change. This suggests that KRAS mutation status might be involved in acquiring oxidative phenotype. KRAS mutated polyps had higher Vmax values and elevated MOM permeability as compared to the control. BRAF mutated CRC and polyps had reduced respiration and altered MOM permeability, indicating a glycolytic phenotype. To conclude, prognostic biomarkers KRAS and BRAF are likely related to the metabolic phenotype in CRC and polyps. Assessment of the tumor mitochondrial ATP synthesis could be a potential component of patient risk stratification.

scholarly journals Moderation of mitochondrial respiration mitigates metabolic syndrome of aging

2020 ◽  
Vol 117 (18) ◽  
pp. 9840-9850 ◽  
Author(s):  
Mojdeh Tavallaie ◽  
Ramouna Voshtani ◽  
Xinxian Deng ◽  
Yixue Qiao ◽  
Faqin Jiang ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Mitochondrial Respiration ◽  
Mitochondrial Dynamics ◽  
Atp Synthesis ◽  
Control Group ◽  
Standard Diet ◽  
Ros Production ◽  
Metabolic Complications ◽  
Age Related ◽  
Mitochondrial Functions

Deregulation of mitochondrial dynamics leads to the accumulation of oxidative stress and unhealthy mitochondria; consequently, this accumulation contributes to premature aging and alterations in mitochondria linked to metabolic complications. We postulate that restrained mitochondrial ATP synthesis might alleviate age-associated disorders and extend healthspan in mammals. Herein, we prepared a previously discovered mitochondrial complex IV moderate inhibitor in drinking water and orally administered to standard-diet-fed, wild-type C57BL/6J mice every day for up to 16 mo. No manifestation of any apparent toxicity or deleterious effect on studied mouse models was observed. The impacts of an added inhibitor on a variety of mitochondrial functions were analyzed, such as respiratory activity, mitochondrial bioenergetics, and biogenesis, and a few age-associated comorbidities, including reactive oxygen species (ROS) production, glucose abnormalities, and obesity in mice. It was found that mitochondrial quality, dynamics, and oxidative metabolism were greatly improved, resulting in lean mice with a specific reduction in visceral fat plus superb energy and glucose homeostasis during their aging period compared to the control group. These results strongly suggest that a mild interference in ATP synthesis through moderation of mitochondrial activity could effectively up-regulate mitogenesis, reduce ROS production, and preserve mitochondrial integrity, thereby impeding the onset of metabolic syndrome. We conclude that this inhibitory intervention in mitochondrial respiration rectified the age-related physiological breakdown in mice by protecting mitochondrial function and markedly mitigated certain undesired primary outcomes of metabolic syndrome, such as obesity and type 2 diabetes. This intervention warrants further research on the treatment of metabolic syndrome of aging in humans.

scholarly journals Prognostic Significance of DR-70 Levels in Dysplastic Colorectal Polyps

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Atakan Yesil ◽  
Gul Babacan Abanonu ◽  
Yasar Colak ◽  
Nurcan Paker ◽  
Can Gonen
Keyword(s):  
Prognostic Significance ◽  
Serum Levels ◽  
Colorectal Polyps ◽  
Adenomatous Polyps ◽  
Control Group ◽  
Low Grade ◽  
Colon Polyps ◽  
High Grade ◽  
Polyp Size ◽  
Potential Marker

Background. To investigate the relationship between DR-70 serum levels and dysplastic colon polyps.Materials and Methods. A total of 130 patients with adenomatous polyps detected by colonoscopy and divided into two groups including low versus high grade polyp, along with 50 healthy blood donors were included in the study. Blood samples from each participant were analyzed for serum CEA and DR-70 levels.Results. No statistically significant differences were observed between the two groups in terms of age or gender. The median DR-70 level was 0.5 μg/mL in the healthy control group and 1.1 μg/mL in group 1b (i.e., the high grade polyp) (P<0.001). DR-70 was higher in group 1b as compared to group 1a (P<0.001). However, the median DR-70 values for the low grade polyp group (i.e., group 1a) and the control group were similar (P=0.067). In order to determine independent predictors of high grade dysplasia, CEA, DR-70, polyp size, and age parameters were subjected to multiple logistical regression analyses via the Enter method; the model was statistically significant (P<0.001).Conclusions. DR-70, a marker used to measure FDP, which is generated by all major cancers, is a potential marker to identify patients with advanced adenomatous polyps, that is, precursors of colorectal cancer.

CLINICAL SIGNIFICANCE OF SERUM CAVEOLIN-1 LEVELS IN GASTRIC CANCER PATIENTS

2018 ◽  
Vol 40 (4) ◽  
pp. 323-327 ◽  
Author(s):  
F Tas ◽  
S Karabulut ◽  
K Erturk ◽  
D Duranyildiz
Keyword(s):  
Gastric Cancer ◽  
Cancer Patients ◽  
Histological Grade ◽  
Clinical Importance ◽  
Disease Stage ◽  
Control Group ◽  
Tissue Samples ◽  
Caveolin 1 ◽  
Study Results ◽  
Gastric Cancer Patients

Aim: Caveolin-1 plays a significant role in the pathogenesis of various carcinomas and its expression affects the survival of cancer patients. However, the molecular function of caveolin-1 and its possible clinical importance has remained uncertain in gastric cancer. No clinical trial has examined serum caveolin-1 levels in gastric cancer patients so far, instead all available results were provided from studies conducted on tissue samples. In the current study, we analyzed the soluble serum caveolin-1 levels in gastric cancer patients, and specified its associations with the clinical factors and prognosis. Material and Methods: Sixty-three patients with pathologically confirmed gastric cancer were enrolled into the trial. Serum caveolin-1 concentrations were detected by ELISA method. Thirty healthy subjects were also included in the study. Results: The median age of patients was 62 years, ranging from 28 to 82 years. The serum caveolin-1 levels in gastric cancer patients were significantly higher than those in control group (p < 0.001). The common clinical parameters including patient age, sex, lesion localization, histopathology, histological grade, disease stage, and various serum tumor markers (e.g. LDH, CEA, and CA 19.9) were not found to be associated with serum caveolin-1 levels (p > 0.05). Similarly, no correlation existed between serum caveolin-1 concentration and chemotherapy responsiveness (p = 0.93). Furthermore, serum caveolin-1 level was not found to have a prognostic role (p = 0.16). Conclusion: Even though it is neither predictive nor prognostic, serum caveolin-1 level may be a valuable diagnostic indicator in patients with gastric cancer. Key

scholarly journals Arginase Isoform Expression in Chronic Rhinosinusitis

2019 ◽  
Vol 8 (11) ◽  
pp. 1809 ◽  
Author(s):  
Diana Vlad ◽  
Silviu Albu
Keyword(s):  
Nitric Oxide ◽  
Chronic Rhinosinusitis ◽  
Defense Mechanisms ◽  
Upper Airway ◽  
Control Group ◽  
Mrna Levels ◽  
Tissue Samples ◽  
Endoscopic View ◽  
Important Regulator ◽  
Arginase I

Nitric oxide (NO) has emerged as an important regulator of upper airway inflammation, mainly as part of the local naso-sinusal defense mechanisms. Increased arginase activity can reduce NO levels by decreasing the availability of its precursor, L-arginine. Chronic rhinosinusitis (CRS) has been associated with low levels of nasal nitric oxide (nNO). Thus, the present study investigates the activity of arginase I (ARG1) and II (ARG2) in CRS and its possible involvement in the pathogenesis of this disease. Under endoscopic view, tissue samples of pathologic (n = 36) and normal (n = 29) rhinosinusal mucosa were collected. Arginase I and II mRNA levels were measured using real-time PCR. Our results showed low arginase I activity in all samples. The levels of ARG2 were significantly higher in patients with chronic rhinosinusitis compared to the control group (fold regulation (FR) 2.22 ± 0.42 vs. 1.31 ± 0.21, p = 0.016). Increased ARG2 expression was found in patients with CRS without nasal polyposis (FR 3.14 ± 1.16 vs. 1.31 ± 0.21, p = 0.0175), in non-allergic CRS (FR 2.55 ± 0.52 vs. 1.31 ± 0.21, p = 0.005), and non-asthmatic CRS (FR 2.42 ± 0.57 vs. 1.31 ± 0.21, p = 0.028). These findings suggest that the upregulation of ARG2 may play a role in the pathology of a distinctive phenotype of CRS.

scholarly journals The Effect of Zingiber officinale on the Spleen Tissue and Antibody Titer of Broiler Chickens

2019 ◽  
Vol 36 (01) ◽  
pp. 046-050
Author(s):  
Alireza Taghdisi ◽  
Sajjad Hejazi
Keyword(s):  
Broiler Chickens ◽  
Zingiber Officinale ◽  
Control Group ◽  
White Pulp ◽  
Broiler Chicks ◽  
Pulp Tissue ◽  
Tissue Samples ◽  
Serum Factors ◽  
Spleen Tissue ◽  
Significant Difference

Introduction Increasing the immune system's function of fighting infectious diseases is very important in the poultry industry. Ginger, scientifically known as Zingiber officinale, belongs to the Zingiberaceae family. The use of ginger in the diet of poultry increases serum levels of superoxide dismutase enzymes and glutathione peroxidase, which are considered to be important antioxidant enzymes. The main objective of the present study is to evaluate the effect of ginger on the spleen tissue of broiler chickens. Material and Methods The specimens comprised 2 groups of 20 Ross breed broiler chicks, for 42 days and were then, examined and tested. The diet was supplemented with 1 g/kg of ginger powder from the beginning of the rearing period. Blood samples of the chicks were randomly collected to measure the levels of hemagglutination (HI). The removed spleens were fixed with 10% formalin buffer. The specimens were cut in 5-micron diameters and stained with hematoxylin and eosin. Results and Conclusion There was a statistically significant difference in the mean of HI blood titers between the chicks in the growth period and final period groups (p < 0.05). The white-pulp tissue samples were more clearly seen in the treatment group than in the control group, and also, it was observed that the wall of the central artery of the white pulp was thicker in the ginger-treated group as compared with the control group. The nutritional value of ginger may vary. Thus, it is necessary to investigate the effect of this plant final on weight gain; the serum factors associated with the metabolic chart, and the response of the immune system to this plant.

scholarly journals Clip placement to prevent delayed bleeding after colonic endoscopic mucosal resection (CLIPPER): study protocol for a randomized controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ayla S. Turan ◽  
◽  
Leon M. G. Moons ◽  
Ramon-Michel Schreuder ◽  
Erik J. Schoon ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
The Netherlands ◽  
Endoscopic Mucosal Resection ◽  
Intervention Group ◽  
Proximal Colon ◽  
Control Group ◽  
Colon Polyps ◽  
Delayed Bleeding ◽  
Randomized Controlled ◽  
Mucosal Resection

Abstract Background Endoscopic mucosal resection (EMR) for large colorectal polyps is in most cases the preferred treatment to prevent progression to colorectal carcinoma. The most common complication after EMR is delayed bleeding, occurring in 7% overall and in approximately 10% of polyps ≥ 2 cm in the proximal colon. Previous research has suggested that prophylactic clipping of the mucosal defect after EMR may reduce the incidence of delayed bleeding in polyps with a high bleeding risk. Methods The CLIPPER trial is a multicenter, parallel-group, single blinded, randomized controlled superiority study. A total of 356 patients undergoing EMR for large (≥ 2 cm) non-pedunculated polyps in the proximal colon will be included and randomized to the clip group or the control group. Prophylactic clipping will be performed in the intervention group to close the resection defect after the EMR with a distance of < 1 cm between the clips. Primary outcome is delayed bleeding within 30 days after EMR. Secondary outcomes are recurrent or residual polyps and clip artifacts during surveillance colonoscopy after 6 months, as well as cost-effectiveness of prophylactic clipping and severity of delayed bleeding. Discussion The CLIPPER trial is a pragmatic study performed in the Netherlands and is powered to determine the real-time efficacy and cost-effectiveness of prophylactic clipping after EMR of proximal colon polyps ≥ 2 cm in the Netherlands. This study will also generate new data on the achievability of complete closure and the effects of clip placement on scar surveillance after EMR, in order to further promote the debate on the role of prophylactic clipping in everyday clinical practice. Trial registration ClinicalTrials.gov NCT03309683. Registered on 13 October 2017. Start recruitment: 05 March 2018. Planned completion of recruitment: 31 August 2021.

scholarly journals Expression of Estrogen Receptor α by Decidual Macrophages in Preeclampsia

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 191 ◽  
Author(s):  
Polina Vishnyakova ◽  
Anastasiya Poltavets ◽  
Maria Nikitina ◽  
Konstantin Midiber ◽  
Liudmila Mikhaleva ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Late Onset ◽  
Normal Pregnancy ◽  
Estrogen Receptor Α ◽  
Control Group ◽  
Tissue Fluid ◽  
Tissue Samples ◽  
Cultural Methods ◽  
Anti Inflammatory ◽  
Early Onset Preeclampsia

Preeclampsia is a gestation-associated hypertensive syndrome that threatens the life and health of the mother and the child. The condition is presumably caused by systemic failure with a strong involvement of innate immunity. In particular, it has been associated with flexible phenotypes of macrophages, which depend on the molecules circulating in the blood and tissue fluid, such as cytokines and hormones. This study aimed at a comparative evaluation of pro-inflammatory (TNFα) and anti-inflammatory (CD206, MMP9, HGF) markers, as well as the levels of estrogen receptor α, expressed by decidual macrophages in normal pregnancy and in patients with early- and late-onset preeclampsia. The tissue samples of decidua basalis were examined by immunohistochemistry and Western blotting. Isolation of decidual macrophages and their characterization were performed using cultural methods, flow cytometry and real-time PCR. Over 50% of the isolated decidual macrophages were positive for the pan-macrophage marker CD68. In the early-onset preeclampsia group, the levels of estrogen receptor α in decidua were significantly decreased. Furthermore, significantly decreased levels of HGF and CD206 were observed in both preeclampsia groups compared with the control group. The observed downregulation of estrogen receptor α, HGF and CD206 may contribute to the balance of pro- and anti-inflammatory macrophages and thereby to pathogenesis of preeclampsia.

scholarly journals Genes associated with inflammation and bone remodeling are highly expressed in the bone of patients with the early-stage cam-type femoroacetabular impingement

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Guanying Gao ◽  
Ruiqi Wu ◽  
Rongge Liu ◽  
Jianquan Wang ◽  
Yingfang Ao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Tissue ◽  
Bone Remodeling ◽  
Femoroacetabular Impingement ◽  
Early Stage ◽  
Control Group ◽  
Tissue Samples ◽  
Expression Levels ◽  
Normal Bone ◽  
Impingement Zone

Abstract Background Recent studies have shown high expression levels of certain inflammatory, anabolic, and catabolic genes in the articular cartilage from the impingement zone of the hips with femoroacetabular impingement (FAI), representing an increased metabolic state. Nevertheless, little is known about the molecular properties of bone tissue from the impingement zone of hips with FAI. Methods Bone tissue samples from patients with early-stage cam-type FAI were collected during hip arthroscopy for treatment of cam-type FAI. Control bone tissue samples were collected from six patients who underwent total hip replacement because of a femoral neck fracture. Quantitative real-time polymerase chain reaction (PCR) was performed to determine the gene expression associated with inflammation and bone remodeling. The differences in the gene expression in bone tissues from the patients with early-stage cam-type FAI were also evaluated based on clinical parameters. Results In all, 12 patients with early-stage cam-type FAI and six patients in the control group were included in this study. Compared to the control samples, the bone tissue samples from patients with FAI showed higher expression levels of interleukin-6 (IL-6), alkaline phosphatase (ALP), receptor activator of nuclear factor-kB ligand (RANKL), and osteoprotegerin (OPG) (P < 0.05). IL-1 expression was detected only in the control group. On the other hand, there was no significant difference in IL-8 expression between the patients with FAI and the control group. The patients with FAI having a body mass index (BMI) of >24 kg/m2 showed higher ALP expression (P < 0.05). Further, the expression of IL-6 and ALP was higher in the patients with FAI in whom the lateral center-edge angle was >30° (P < 0.05). Conclusions Our results indicated the metabolic condition of bone tissues in patients with early-stage cam-type FAI differed from that of normal bone in the femoral head-neck junction. The expression levels of the genes associated with inflammation and bone remodeling were higher in the bone tissue of patients with early-stage cam-type FAI than in the patients with normal bone tissue.

scholarly journals Effects of Dietary Inclusion of Bilberry and Walnut Leaves Powder on the Digestive Performances and Health of Tetra SL Laying Hens

Animals ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 823 ◽  
Author(s):  
Roua Gabriela Popescu ◽  
Sorina Nicoleta Voicu ◽  
Gratiela Gradisteanu Pircalabioru ◽  
Alina Ciceu ◽  
Sami Gharbia ◽  
...  
Keyword(s):  
Histological Analysis ◽  
Specific Activity ◽  
Basal Diet ◽  
Intestinal Content ◽  
Final Concentration ◽  
Control Group ◽  
Villus Height ◽  
Tissue Samples ◽  
Walnut Leaves ◽  
Digestive Health

The purpose of this study was to examine the effects of dietary inclusion of two additives at the final concentration of 0.5% bilberry (E1) and 1% walnut (E2) leaves powder in the basal diet on digestive health of hens. A total number of 90 Tetra SL hens were divided into two experimental groups (E1 and E2) and one control group (C) consisting of 30 hens each. After four weeks, 10 hens of each group were sacrificed and tissue samples and intestinal content were taken from the duodenum, jejunum, and cecum in order to perform histological, enzymatic, and microbiota analyses. In groups E1 and E2, the histological analysis showed a significant increase of villus height, resulting probably in increased absorption of nutrients in duodenum and jejunum. A decrease in the specific activity of alpha-amylase and trypsin in E1 and E2 for both duodenum and jejunum compared to the control one was also recorded. In addition, the maltase and invertase specific activity in duodenum increased, a tendency that was kept for maltase but not for invertase in jejunum. The cecal microbiota of E1 and E2 individuals was characterized by an increase of Firmicutes and Lactobacilli and a decrease of Enterobacteriaceae. In conclusion, our results indicate that bilberry and walnut leaves additives in feed may improve the health status of the poultry gastrointestinal tract.

Mitochondrial Inhibition Prior to Oxygen-Withdrawal Facilitates the Occurrence of Hypoxia-Induced Spreading Depression in Rat Hippocampal Slices

2006 ◽  
Vol 96 (1) ◽  
pp. 492-504 ◽  
Author(s):  
Florian J. Gerich ◽  
Sebastian Hepp ◽  
Irmelin Probst ◽  
Michael Müller
Keyword(s):  
Mitochondrial Respiration ◽  
Spreading Depression ◽  
Hippocampal Slices ◽  
Atp Synthesis ◽  
Atp Depletion ◽  
Mitochondrial Uncoupling ◽  
Ca1 Neurons ◽  
Optical Signals ◽  
Nitropropionic Acid ◽  
Carbonyl Cyanide

Oxygen withdrawal blocks mitochondrial respiration. In rat hippocampal slices, this triggers a massive depolarization of CA1 neurons and a negative shift of the extracellular DC potential, the characteristic sign of hypoxia-induced spreading depression (HSD). To unveil the contribution of mitochondria to the sensing of hypoxia and the ignition of HSD, we modified mitochondrial function. Mitochondrial uncoupling by carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP, 1 μM) prior to hypoxia hastened the onset and shortened the duration of HSD. Blocking mitochondrial ATP synthesis by oligomycin (10 μg/ml) was without effect. Inhibition of mitochondrial respiration by rotenone (20 μM), diphenyleneiodonium (25 μM), or antimycin A (20 μM) also hastened HSD onset and shortened HSD duration. 3-nitropropionic acid (1 mM) increased HSD duration. Cyanide (100 μM) hastened HSD onset and increased HSD duration. At higher concentrations, cyanide (1 mM), azide (2 mM), and FCCP (10 μM) triggered SD episodes on their own. Compared with control HSD, the spatial extent of the intrinsic optical signals of cyanide- and azide-induced SDs was more pronounced. Monitoring NADH (nicotinamide adenine dinucleotide) and FAD (flavin adenine dinucleotide) autofluorescence and mitochondrial membrane potential verified the mitochondrial targeting by the drugs used. Except 1 mM cyanide, no treatment reduced cellular ATP levels severely and no correlation was found between ATP, NADH, or FAD levels and the time to HSD onset. Therefore ATP depletion or a cytosolic reducing shift due to NADH/FADH2 accumulation cannot serve as a general explanation for the hastening of HSD onset on mitochondrial inhibition. Additional redox couples (glutathione) or events downstream of the mitochondrial depolarization need to be considered.

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