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FASEB Journal : Official Publication of... Jul 2024To investigate the effects of heavy-load strength training during (neo-)adjuvant chemotherapy in women with breast cancer on muscle strength, body composition, muscle... (Randomized Controlled Trial)
Randomized Controlled Trial
Effects of heavy-load strength training during (neo-)adjuvant chemotherapy on muscle strength, muscle fiber size, myonuclei, and satellite cells in women with breast cancer.
To investigate the effects of heavy-load strength training during (neo-)adjuvant chemotherapy in women with breast cancer on muscle strength, body composition, muscle fiber size, satellite cells, and myonuclei. Women with stage I-III breast cancer were randomly assigned to a strength training group (ST, n = 23) performing supervised heavy-load strength training twice a week during chemotherapy, or a usual care control group (CON, n = 17). Muscle strength and body composition were measured and biopsies from m. vastus lateralis collected before the first cycle of chemotherapy (T0) and after chemotherapy and training (T1). Muscle strength increased significantly more in ST than in CON in chest-press (ST: +10 ± 8%, p < .001, CON: -3 ± 5%, p = .023) and leg-press (ST: +11 ± 8%, p < .001, CON: +3 ± 6%, p = .137). Both groups reduced fat-free mass (ST: -4.9 ± 4.0%, p < .001, CON: -5.2 ± 4.9%, p = .004), and increased fat mass (ST: +15.3 ± 16.5%, p < .001, CON: +16.3 ± 19.8%, p = .015) with no significant differences between groups. No significant changes from T0 to T1 and no significant differences between groups were observed in muscle fiber size. For myonuclei per fiber a non-statistically significant increase in CON and a non-statistically significant decrease in ST in type I fibers tended (p = .053) to be different between groups. Satellite cells tended to decrease in ST (type I: -14 ± 36%, p = .097, type II: -9 ± 55%, p = .084), with no changes in CON and no differences between groups. Strength training during chemotherapy improved muscle strength but did not significantly affect body composition, muscle fiber size, numbers of satellite cells, and myonuclei compared to usual care.
Topics: Humans; Female; Muscle Strength; Breast Neoplasms; Resistance Training; Satellite Cells, Skeletal Muscle; Middle Aged; Adult; Chemotherapy, Adjuvant; Body Composition; Muscle Fibers, Skeletal; Neoadjuvant Therapy; Aged
PubMed: 38953567
DOI: 10.1096/fj.202400634R -
BJU International Jul 2024To evaluate the utility of the 17-gene Genomic Prostate Score® (GPS; MDxHealth, Irvine, CA, USA) performed on prostate cancer at the positive margin of the radical...
OBJECTIVES
To evaluate the utility of the 17-gene Genomic Prostate Score® (GPS; MDxHealth, Irvine, CA, USA) performed on prostate cancer at the positive margin of the radical prostatectomy (RP) for its association with risk of subsequent biochemical recurrence (BCR).
PATIENTS AND METHODS
We designed a case-cohort for the outcome of BCR, selecting 223 from a cohort of 813 RP patients treated at Johns Hopkins from 2008 to 2017 with positive margins and available clinical data; of these, 213 had available tissue and clinical data. RNA was isolated from formalin-fixed paraffin-embedded tumour tissue adjacent to the positive surgical margin and the GPS was evaluable in 203 of these patients with a score ranging from 0 to 100, with higher scores indicating higher risk. All patients underwent RP with or without adjuvant radiation therapy (ART). The statistical analysis employed Cox proportional hazards regression models for outcome of BCR weighted for case-cohort design.
RESULTS
In univariable analysis, every 20-unit increase in the GPS was associated with a nearly threefold increase in risk of BCR (hazard ratio [HR] per 20 units 2.82, P < 0.001). In a multivariable Cox model adjusted for age, race, Cancer of the Prostate Risk Assessment Postsurgical score, Grade Group at the positive margin, and ART, the GPS was significantly associated with BCR (HR 1.56 per 20 units; 95% confidence interval 1.11-2.19; P = 0.011). The study is limited by its retrospective and single institution design.
CONCLUSIONS
The GPS at the positive surgical margin could help stratify prognosis and inform clinical decision-making regarding adjuvant therapy after RP.
PubMed: 38953550
DOI: 10.1111/bju.16445 -
Journal of Biochemical and Molecular... Jul 2024Cyclophosphamide (CP) is an antineoplastic drug widely used in chemotherapy. Curcumin (CUR) and piperine (PP) show a protective effect on neurodegenerative and...
Cyclophosphamide (CP) is an antineoplastic drug widely used in chemotherapy. Curcumin (CUR) and piperine (PP) show a protective effect on neurodegenerative and neurological diseases. This research was designed to measure several biochemical parameters in the brain tissue of CP-applied rats to investigate the impact of combined CUR-PP administration. The study evaluated six groups of eight rats: Group 1 was the control; Groups 2 and 3 were administered 200 or 300 mg/kg CUR-PP via oral gavage; Group 4 received only 200 mg/kg CP on day 1; Groups 5 and 6 received CP + CUR-PP for 7 days. Data from all parameters indicated that CP caused brain damage. Phosphorylated TAU (pTAU), amyloid-beta peptide 1-42 (Aβ1-42), glutamate (GLU), and gamma amino butyric acid (GABA) parameters were the same in Groups 4, 5, and 6. On the other hand, 8-hydroxy-2-deoxyguanosine (8-OHdG), nitric oxide (NO), interleukin-6 (IL-6), nuclear factor kappa beta (NF-kβ), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNF-α) levels in the CP + CUR-PP groups were lower than those in the CP group (p < 0.05). However, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH) parameters were higher in the CP + CUR-PP groups compared to the CP group (p < 0.05). It is thought that the similarity of Groups 5 and 6 with Group 4 in Aβ1-42, pTAU, GLU, and GABA parameters hinder the determination of treatment protection however, they might have a therapeutic effect if the applied dose or study duration were changed. This study attempted to evaluate the effects of a CUR-PP combination on CP-induced brain damage in rats by measuring biochemical parameters and performing histopathological examinations. Based on the findings, this CUR-PP combination could be considered an alternative medicine option in cases with conditions similar to those evaluated in this study.
Topics: Animals; Polyunsaturated Alkamides; Benzodioxoles; Curcumin; Piperidines; Alkaloids; Rats; Cyclophosphamide; Male; Brain Injuries; Rats, Wistar; Brain; Oxidative Stress; Neuroprotective Agents
PubMed: 38953502
DOI: 10.1002/jbt.23760 -
Journal of Crohn's & Colitis Jul 2024The disease severity index (DSI) encapsulates the inflammatory bowel disease (IBD) burden but requires endoscopic investigations. This study developed a non-invasive DSI...
INTRODUCTION
The disease severity index (DSI) encapsulates the inflammatory bowel disease (IBD) burden but requires endoscopic investigations. This study developed a non-invasive DSI using faecal calprotectin (DSI-fCal) and faecal myeloperoxidase (DSI-fMPO) instead of colonoscopy.
METHODS
Adults with IBD were recruited prospectively. Baseline biomarker concentrations were used to develop DSI-fCal and DSI-fMPO, and these were correlated with the original DSI, IBD-symptoms, endoscopic activity, and quality-of-life (QoL). Area under the receiver-operating-characteristics curves (AUROC) assessed DSI-fCal/DSI-fMPO as predictors of clinical and biochemical remission at six months (symptom remission and fCal <150 μg/g, respectively), and a complicated IBD-course at 24 months (disease relapse needing escalation of biologicals/immunomodulators/recurrent corticosteroids, IBD-hospitalisations/surgeries). Multivariable logistic regression assessed the utility of DSI-fCal/DSI-fMPO in predicting a complicated IBD-course at 24 months.
RESULTS
In total, 171 patients were included (Crohn's disease=99, female=90, median age=46y (IQR 36-59)). DSI-fCal and DSI-fMPO correlated with the original DSI (r>0.9, p<0.001), endoscopic indices (r=0.45-0.49, p<0.001), IBD-symptoms (r=0.53-0.58, p<0.001) and QoL (r=-0.57-0.58, p<0.001). Baseline DSI-fCal (AUROC=0.79, 95% CI 0.65-0.92) and DSI-fMPO (AUROC=0.80, 95% CI 0.67-0.93) were associated with 6-month clinical and biochemical remission. DSI-fCal (AUROC=0.83, 95% CI 0.77-0.89) and DSI-fMPO (AUROC=0.80, 95% CI 0.73-0.87) performed similarly in predicting a complicated IBD-course to the original DSI (pdifference>0.05). The non-invasive DSI was independently associated with a complicated IBD-course on multivariable analyses (DSI-fCal28, aOR=6.04, 95% CI 2.42-15.08; DSI-fMPO25, aOR=7.84, 95% CI 2.96-20.73).
CONCLUSIONS
The DSI-fCal and DSI-fMPO perform similarly in prognosticating the longitudinal disease course as the original DSI, whilst avoiding a need for an endoscopic assessment.
PubMed: 38953471
DOI: 10.1093/ecco-jcc/jjae106 -
MBio Jul 2024Dimorphism is known among the etiologic agents of endemic mycoses as well as in filamentous . Under appropriate thermal conditions, mononuclear yeast forms alternate...
Dimorphism is known among the etiologic agents of endemic mycoses as well as in filamentous . Under appropriate thermal conditions, mononuclear yeast forms alternate with multi-nucleate hyphae. Here, we describe a dimorphic mucoralean fungus obtained from the sputum of a patient with Burkitt lymphoma and ongoing graft-versus-host reactions. The fungus is described as sp. nov. Laboratory studies were performed to simulate temperature-dependent dimorphism, with two environmental strains and as controls. Both strains could be induced to form multinucleate arthrospores and subsequent yeast-like cells . Multilateral yeast cells emerge in all three at elevated temperatures. This morphological transformation appears to occur at body temperature since the yeast-like cells were observed in the lungs of our immunocompromised patient. The microscopic appearance of the yeast-like cells in the clinical samples is easily confused with that of . The ecological role of yeast forms in is discussed.IMPORTANCEMucormycosis is a devastating disease with high morbidity and mortality in susceptible patients. Accurate diagnosis is required for timely clinical management since antifungal susceptibility differs between species. Irregular hyphal elements are usually taken as the hallmark of mucormycosis, but here, we show that some species may also produce yeast-like cells, potentially being mistaken for or . We demonstrate that the dimorphic transition is common in species and can be driven by many factors. The multi-nucleate yeast-like cells provide an effective parameter to distinguish mucoralean infections from similar yeast-like species in clinical samples.
PubMed: 38953355
DOI: 10.1128/mbio.00144-24 -
Zhongguo Yi Xue Ke Xue Yuan Xue Bao.... Jun 2024Objective To explore the diagnostic value of ultrasound for thyroid nodules with a spoke-wheel blood flow pattern.Methods The clinical data of the patients with thyroid...
Objective To explore the diagnostic value of ultrasound for thyroid nodules with a spoke-wheel blood flow pattern.Methods The clinical data of the patients with thyroid nodules presenting a spoke-wheel blood flow pattern examined by ultrasound were collected,and the gray-scale ultrasound features of the nodules were recorded.The diagnostic performance of the Thyroid Imaging Reporting and Data System by American College of Radiology (ACR TI-RADS),Chinese Thyroid Imaging Reporting and Data System (C-TIRADS),and combined specific indicators for the thyroid nodules with a spoke-wheel blood flow pattern was evaluated by comparison with the pathological results,which was regarded as the gold standard.Results A total of 64 patients with thyroid nodules were finally included,including 47 patients with malignant nodules and 17 patients with benign nodules.In addition to the general ultrasound features,central scar mostly appeared in malignant nodules (=5.968,=0.015),while central coarse calcification was more common in benign nodules (=10.899,=0.001).After the combination of central scar and central gross calcification,the diagnostic performance of ACR TI-RADS and C-TIRADS was improved (both <0.001).Conclusions When the thyroid nodule shows a spoke-wheel blood flow pattern,one should be cautious of the possibility of malignancy.Combining central scar and central coarse calcification can improve the accuracy of ultrasonic diagnosis.
Topics: Humans; Thyroid Nodule; Middle Aged; Male; Female; Ultrasonography; Adult; Aged; Young Adult
PubMed: 38953260
DOI: 10.3881/j.issn.1000-503X.15894 -
Zhongguo Yi Xue Ke Xue Yuan Xue Bao.... Jun 2024Objective To explore the relationship between the expression levels of microRNA-155 (miR-155) and suppressor of cytokine signaling 1 (SOCS1) in the colonic mucosal...
[Correlations Between the Expression of MicroRNA-155 and Suppressor of Cytokine Signaling 1 in Colonic Mucosal Tissue and Disease Severity in Patients With Ulcerative Colitis].
Objective To explore the relationship between the expression levels of microRNA-155 (miR-155) and suppressor of cytokine signaling 1 (SOCS1) in the colonic mucosal tissue of patients with ulcerative colitis (UC) and the severity of the disease.Methods A total of 130 UC patients admitted to the Second Affiliated Hospital of Hebei North University from September 2021 to June 2023 were selected.According to the modified Mayo score system,the patients were assigned into an active stage group (=85) and a remission stage group (=45).According to the modified Truelove and Witts classification criteria,the UC patients at the active stage were assigned into a mild group (=35),a moderate group (=30),and a severe group (=20).A total of 90 healthy individuals who underwent colonoscopy for physical examination or those who had normal colonoscopy results after single polypectomy and excluded other diseases were selected as the control group.The colonic mucosal tissues of UC patients with obvious lesions and the colonic mucosal tissue 20 cm away from the anus of the control group were collected.The levels of miR-155 and SOCS1 mRNA in tissues were determined by fluorescence quantitative PCR,and the expression of SOCS1 protein in tissues was determined by immunohistochemistry.The correlations of the levels of miR-155 and SOCS1 mRNA in the colonic mucosal tissue with the modified Mayo score of UC patients were analyzed.The values of the levels of miR-155 and SOCS1 mRNA in predicting the occurrence of severe illness in the UC patients at the active stage were evaluated.Results Compared with the control group and the remission stage group,the active stage group showed up-regulated expression level of miR-155,down-regulated level of SOCS1 mRNA,and decreased positive rate of SOCS1 protein in the colonic mucosal tissue (all <0.001).The expression level of miR-155 and modified Mayo score in colonic mucosal tissues of UC patients at the active stage increased,while the mRNA level of SOCS1 was down-regulated as the disease evolved from being mild to severe (all <0.001).The modified Mayo score was positively correlated with the miR-155 level and negative correlated with the mRNA level of SOCS1 in colonic mucosal tissues of UC patients (all <0.001).The high miR-155 level (=2.762,95%=1.284-5.944,=0.009),low mRNA level of SOCS1 (=2.617,95%=1.302-5.258,=0.007),and modified Mayo score≥12 points (=3.232,95%=1.450-7.204,=0.004) were all risk factors for severe disease in the UC patients at the active stage.The area under curve of miR-155 combined with SOCS1 mRNA in predicting severe illness in the UC patients at the active stage was 0.920.Conclusions The expression levels of miR-155 and SOCS1 mRNA were correlated with the disease severity in the UC patients at the active stage.The combination of the two indicators demonstrates good performance in predicting the occurrence of severe illness in UC patients at the active stage.
Topics: Humans; MicroRNAs; Colitis, Ulcerative; Suppressor of Cytokine Signaling 1 Protein; Intestinal Mucosa; Severity of Illness Index; Colon; Female; Male; Middle Aged; Adult
PubMed: 38953257
DOI: 10.3881/j.issn.1000-503X.15863 -
Lung India : Official Organ of Indian... Jul 2024Modalities to improve tissue acquisition during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) have been investigated. Endobronchial...
BACKGROUND
Modalities to improve tissue acquisition during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) have been investigated. Endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy (EBUS-TMC) is a modality to obtain larger histological samples by inserting a cryoprobe into the mediastinal lesion. We aimed to study the diagnostic yield and safety of EBUS-TMC.
METHODS
We performed a systematic search of the PubMed and Embase databases to extract the relevant studies. We then performed a meta-analysis to calculate the diagnostic yield of EBUS-TMC and compare it with EBUS-TBNA.
RESULTS
Following a systematic search, we identified 14 relevant studies (869 patients undergoing EBUS-TMC and EBUS-TBNA). We then performed a meta-analysis of the diagnostic yield of EBUS-TMC and EBUS-TBNA from studies wherein both procedures were performed. The pooled diagnostic yield of EBUS-TMC was 92% (95% confidence interval [CI], 89%-95%). The pooled diagnostic yield of EBUS-TBNA was 81% (95% CI, 77%-85%). The risk difference in yield was 11% (95% CI, 6%-15%, I2 = 0%) when EBUS-TMC and EBUS-TBNA were compared. The only complication reported commonly with EBUS-TMC was minor bleeding. The complication rate was comparable with EBUS-TBNA.
CONCLUSION
EBUS-TMC provides a greater diagnostic yield with a similar risk of adverse events compared to EBUS-TBNA. Future studies are required to clearly establish which patients are most likely to benefit from this modality.
PubMed: 38953193
DOI: 10.4103/lungindia.lungindia_606_23 -
Journal of Crohn's & Colitis Jul 2024Biomarkers that integrate genetic and environmental factors and predict outcome in complex immune diseases such as inflammatory bowel disease (IBD; including Crohn's...
BACKGROUND & AIMS
Biomarkers that integrate genetic and environmental factors and predict outcome in complex immune diseases such as inflammatory bowel disease (IBD; including Crohn's disease [CD] and ulcerative colitis [UC]) are needed. We showed that morphologic patterns of ileal Paneth cells (Paneth cell phenotype [PCP]; a surrogate for PC function) is one such cellular biomarker for CD. Given the shared features between CD and UC, we hypothesized that PCP is also associated with molecular/genetic features and outcome in UC. Because PC density is highest in the ileum, we further hypothesized that PCP predicts outcome in UC subjects who underwent total colectomy and ileal pouch-anal anastomosis (IPAA).
METHODS
Uninflamed ileal resection margins from UC subjects with colectomy and IPAA were used for PCP and transcriptomic analyses. PCP was defined using defensin 5 immunofluorescence. Genotyping was performed using Immunochip. UC transcriptomic and genotype associations of PCP were incorporated with data from CD subjects to identify common IBD-related pathways and genes that regulate PCP.
RESULTS
The prevalence of abnormal ileal PCP was 27%, comparable to that seen in CD. Combined analysis of UC and CD subjects showed that abnormal PCP was associated with transcriptomic pathways of secretory granule maturation and polymorphisms in innate immunity genes. Abnormal ileal PCP at the time of colectomy was also associated with pouch complications including de novo CD in the pouch and time to first episode of pouchitis.
CONCLUSIONS
Ileal PCP is biologically and clinically relevant in UC and can be used as a biomarker in IBD.
PubMed: 38953127
DOI: 10.1093/ecco-jcc/jjae105 -
Frontiers in Pharmacology 2024Ezetimibe, which lowers cholesterol by blocking the intestinal cholesterol transporter Niemann-Pick C1 like 1, is reported to reduce hepatic steatosis in humans and...
BACKGROUND
Ezetimibe, which lowers cholesterol by blocking the intestinal cholesterol transporter Niemann-Pick C1 like 1, is reported to reduce hepatic steatosis in humans and animals. Here, we demonstrate the changes in hepatic metabolites and lipids and explain the underlying mechanism of ezetimibe in hepatic steatosis.
METHODS
We fed Otsuka Long-Evans Tokushima Fatty (OLETF) rats a high-fat diet (60 kcal % fat) with or vehicle (control) or ezetimibe (10 mg kg) via stomach gavage for 12 weeks and performed comprehensive metabolomic and lipidomic profiling of liver tissue. We used rat liver tissues, HepG2 hepatoma cell lines, and siRNA to explore the underlying mechanism.
RESULTS
In OLETF rats on a high-fat diet, ezetimibe showed improvements in metabolic parameters and reduction in hepatic fat accumulation. The comprehensive metabolomic and lipidomic profiling revealed significant changes in phospholipids, particularly phosphatidylcholines (PC), and alterations in the fatty acyl-chain composition in hepatic PCs. Further analyses involving gene expression and triglyceride assessments in rat liver tissues, HepG2 hepatoma cell lines, and siRNA experiments unveiled that ezetimibe's mechanism involves the upregulation of key phospholipid biosynthesis genes, CTP:phosphocholine cytidylyltransferase alpha and phosphatidylethanolamine N-methyl-transferase, and the phospholipid remodeling gene lysophosphatidylcholine acyltransferase 3.
CONCLUSION
This study demonstrate that ezetimibe improves metabolic parameters and reduces hepatic fat accumulation by influencing the composition and levels of phospholipids, specifically phosphatidylcholines, and by upregulating genes related to phospholipid biosynthesis and remodeling. These findings provide valuable insights into the molecular pathways through which ezetimibe mitigates hepatic fat accumulation, emphasizing the role of phospholipid metabolism.
PubMed: 38953111
DOI: 10.3389/fphar.2024.1406493