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Translational Oncology Jun 2024Considerable studies show that ETS variant 4 (ETV4) plays an important roles in multitudinous tumor. This study investigated its function in cholangiocarcinoma (CCA)...
BACKGROUND
Considerable studies show that ETS variant 4 (ETV4) plays an important roles in multitudinous tumor. This study investigated its function in cholangiocarcinoma (CCA) progression and revealed the underlying mechanisms.
METHODS
The expression of ETV4 in CCA was evaluated using TCGA database and the single-cell analysis based on GSE189903 dataset. ETV4 expression in CCA human specimens was detected by reverse transcription-quantitative PCR, immunohistochemistry, and western blot. Cell Counting Kit-8, EdU, colony formation, wound healing, and Transwell assays were used to analyze the effects of ETV4. Extracellular acidification rate, oxygen consumption rate, glucose uptake, and lactate production were used to measure glycolysis in CAA cells. Western blot was performed to explore glycolysis-related proteins. Tumor growth was evaluated in mice xenograft tumors.
RESULTS
ETV4 was up-regulated in CCA epithelial cells. The high-expression of ETV4 was associated with poor prognosis of patients with CCA. ETV4 overexpression enhanced the proliferation, migration, invasion, and glycolysis of CCA cells; ETV4 silencing led to the contrary effects. Mechanistically, ETV4 activates TGF-β/Smad2/3 signaling pathway. In mice xenograft mode, ETV4 silencing inhibits the tumor growth, the expression of glycolysis-related proteins and TGF-β/Smad2/3 pathway proteins.
CONCLUSIONS
ETV4 functions as an essential factor in the roles of TGF-β1 in CCA cells, and may be a promising target for TGF-β1-mediated CCA progression.
PubMed: 38878613
DOI: 10.1016/j.tranon.2024.102035 -
Cancer Science Jun 2024Application of physical forces, ranging from ultrasound to electric fields, is recommended in various clinical practice guidelines, including those for treating cancers...
Application of physical forces, ranging from ultrasound to electric fields, is recommended in various clinical practice guidelines, including those for treating cancers and bone fractures. However, the mechanistic details of such treatments are often inadequately understood, primarily due to the absence of comprehensive study models. In this study, we demonstrate that an alternating magnetic field (AMF) inherently possesses a direct anti-cancer effect by enhancing oxidative phosphorylation (OXPHOS) and thereby inducing metabolic reprogramming. We observed that the proliferation of human glioblastoma multiforme (GBM) cells (U87 and LN229) was inhibited upon exposure to AMF within a specific narrow frequency range, including around 227 kHz. In contrast, this exposure did not affect normal human astrocytes (NHA). Additionally, in mouse models implanted with human GBM cells in the brain, daily exposure to AMF for 30 min over 21 days significantly suppressed tumor growth and prolonged overall survival. This effect was associated with heightened reactive oxygen species (ROS) production and increased manganese superoxide dismutase (MnSOD) expression. The anti-cancer efficacy of AMF was diminished by either a mitochondrial complex IV inhibitor or a ROS scavenger. Along with these observations, there was a decrease in the extracellular acidification rate (ECAR) and an increase in the oxygen consumption rate (OCR). This suggests that AMF-induced metabolic reprogramming occurs in GBM cells but not in normal cells. Our results suggest that AMF exposure may offer a straightforward strategy to inhibit cancer cell growth by leveraging oxidative stress through metabolic reprogramming.
PubMed: 38877783
DOI: 10.1111/cas.16243 -
Journal of Experimental & Clinical... Jun 2024Breast cancer (BC) is a complex disease, showing heterogeneity in the genetic background, molecular subtype, and treatment algorithm. Historically, treatment strategies...
BACKGROUND
Breast cancer (BC) is a complex disease, showing heterogeneity in the genetic background, molecular subtype, and treatment algorithm. Historically, treatment strategies have been directed towards cancer cells, but these are not the unique components of the tumor bulk, where a key role is played by the tumor microenvironment (TME), whose better understanding could be crucial to obtain better outcomes.
METHODS
We evaluated mitochondrial transfer (MT) by co-culturing Adipose stem cells with different Breast cancer cells (BCCs), through MitoTracker assay, Mitoception, confocal and immunofluorescence analyses. MT inhibitors were used to confirm the MT by Tunneling Nano Tubes (TNTs). MT effect on multi-drug resistance (MDR) was assessed using Doxorubicin assay and ABC transporter evaluation. In addition, ATP production was measured by Oxygen Consumption rates (OCR) and Immunoblot analysis.
RESULTS
We found that MT occurs via Tunneling Nano Tubes (TNTs) and can be blocked by actin polymerization inhibitors. Furthermore, in hybrid co-cultures between ASCs and patient-derived organoids we found a massive MT. Breast Cancer cells (BCCs) with ASCs derived mitochondria (ADM) showed a reduced HIF-1α expression in hypoxic conditions, with an increased ATP production driving ABC transporters-mediated multi-drug resistance (MDR), linked to oxidative phosphorylation metabolism rewiring.
CONCLUSIONS
We provide a proof-of-concept of the occurrence of Mitochondrial Transfer (MT) from Adipose Stem Cells (ASCs) to BC models. Blocking MT from ASCs to BCCs could be a new effective therapeutic strategy for BC treatment.
Topics: Humans; Breast Neoplasms; Female; Mitochondria; Drug Resistance, Neoplasm; Drug Resistance, Multiple; Stem Cells; Adipose Tissue; Cell Line, Tumor; Tumor Microenvironment
PubMed: 38877575
DOI: 10.1186/s13046-024-03087-8 -
European Journal of Sport Science Jun 2024This study investigates whether exercise as a strategy for improving physical fitness at sea level also offers comparable benefits in the unique context of high... (Randomized Controlled Trial)
Randomized Controlled Trial
This study investigates whether exercise as a strategy for improving physical fitness at sea level also offers comparable benefits in the unique context of high altitudes (HA), considering the physiological challenges of hypoxic conditions. Overall, 121 lowlanders who had lived on the Tibetan Plateau for >2 years and were still living at HA during the measurements were randomly classified into four groups. Each individual of the low-intensity (LI), moderate-intensity (MI), and high-intensity (HI) groups performed 20 sessions of aerobic exercise at HA (3680 m) over 4 weeks, while the control group (CG) did not undergo any intervention. Physiological responses before and after the intervention were observed. The LI and MI groups experienced significant improvement in cardiopulmonary fitness (0.27 and 0.35 L/min increases in peak oxygen uptake [ O], both p < 0.05) after exercise intervention, while the hematocrit (HCT) remained unchanged (p > 0.05). However, HI exercise was less efficient for cardiopulmonary fitness of lowlanders (0.02 L/min decrease in O, p > 0.05), whereas both the HCT (1.74 %, p < 0.001) and glomerular filtration rate (18.41 mL/min, p < 0.001) increased with HI intervention. Therefore, LI and MI aerobic exercise, rather than HI, can help lowlanders in Tibet become more acclimated to the HA by increasing cardiopulmonary function and counteracting erythrocytosis.
Topics: Humans; Tibet; Exercise; Altitude; Male; Adult; Acclimatization; Oxygen Consumption; Cardiorespiratory Fitness; Female; Hematocrit; Young Adult; Glomerular Filtration Rate; Physical Fitness; Heart Rate
PubMed: 38874991
DOI: 10.1002/ejsc.12110 -
European Journal of Sport Science Jun 2024We aimed to assess the effects of muscle disuse on muscle strength (MS), muscle mass (MM) and cardiovascular fitness. Databases were scrutinized to identify human... (Meta-Analysis)
Meta-Analysis Review
We aimed to assess the effects of muscle disuse on muscle strength (MS), muscle mass (MM) and cardiovascular fitness. Databases were scrutinized to identify human studies assessing the effects of muscle disuse on both (1) MM and (2) maximal oxygen uptake (VO) and/or MS. Random-effects meta-analysis and meta-regression with initial physical fitness and length of the protocol as a priori determined moderators were performed. We quantitatively analyzed 51 different studies, and the level of significance was set at p < 0.05. Data from the participants in 14 studies showed a decline in both VO (SMD: -0.93; 95% CI: -1.27 to -0.58) and MM (SMD: -0.34; 95% CI: -0.57 to -0.10). Data from 47 studies showed a decline in strength (-0.88; 95% CI: -1.04 to -0.73) and mass (SMD: -0.47; 95% CI: -0.58 to -0.36). MS loss was twice as high as MM loss, but differences existed between anatomical regions. Notably, meta-regression analysis revealed that initial MS was inversely associated with MS decline. VO and MS decline to a higher extent than MM during muscle disuse. We reported a more profound strength loss in subjects with high muscular strength. This is physiologically relevant for athletes because their required muscular strength can profoundly decline during a period of muscle disuse. It should however be noted that a period of muscle disuse can have devastating consequences in old subjects with low muscular strength.
Topics: Humans; Muscle, Skeletal; Muscle Strength; Oxygen Consumption; Cardiorespiratory Fitness
PubMed: 38874988
DOI: 10.1002/ejsc.12093 -
European Journal of Sport Science Jun 2024Blood flow restriction (BFR) is increasingly being used to enhance aerobic performance in endurance athletes. This study examined physiological responses to BFR applied... (Randomized Controlled Trial)
Randomized Controlled Trial
Blood flow restriction (BFR) is increasingly being used to enhance aerobic performance in endurance athletes. This study examined physiological responses to BFR applied in recovery phases within a high-intensity interval training (HIIT) session in trained cyclists. Eleven competitive road cyclists (mean ± SD, age: 28 ± 7 years, body mass: 69 ± 6 kg, peak oxygen uptake: 65 ± 9 mL · kg · min) completed two randomised crossover conditions: HIIT with (BFR) and without (CON) BFR applied during recovery phases. HIIT consisted of six 30-s cycling bouts at an intensity equivalent to 85% of maximal 30-s power (523 ± 93 W), interspersed with 4.5-min recovery. BFR (200 mmHg, 12 cm cuff width) was applied for 2-min in the early recovery phase between each interval. Pulmonary gas exchange (V̇O, V̇CO, and V̇E), tissue oxygen saturation index (TSI), heart rate (HR), and serum vascular endothelial growth factor concentration (VEGF) were measured. Compared to CON, BFR increased V̇CO and V̇E during work bouts (both p < 0.05, dz < 0.5), but there was no effect on V̇O, TSI, or HR (p > 0.05). In early recovery, BFR decreased TSI, V̇O, V̇CO, and V̇E (all p < 0.05, dz > 0.8) versus CON, with no change in HR (p > 0.05). In late recovery, when BFR was released, V̇O, V̇CO, V̇E, and HR increased, but TSI decreased versus CON (all p < 0.05, dz > 0.8). There was a greater increase in VEGF at 3-h post-exercise in BFR compared to CON (p < 0.05, dz > 0.8). Incorporating BFR into HIIT recovery phases altered physiological responses compared to exercise alone.
Topics: Humans; Bicycling; High-Intensity Interval Training; Adult; Heart Rate; Oxygen Consumption; Cross-Over Studies; Male; Young Adult; Pulmonary Gas Exchange; Vascular Endothelial Growth Factor A; Regional Blood Flow; Athletic Performance; Oxygen Saturation
PubMed: 38874956
DOI: 10.1002/ejsc.12107 -
European Journal of Sport Science Jun 2024This study examined the impact of continuous blood flow restriction (BFR) during repeated-sprint exercise (RSE) on acute performance, peripheral, systemic physiological,... (Randomized Controlled Trial)
Randomized Controlled Trial
This study examined the impact of continuous blood flow restriction (BFR) during repeated-sprint exercise (RSE) on acute performance, peripheral, systemic physiological, and perceptual responses. In a randomized crossover design, 26 adult male semi-professional and amateur team-sport players completed two RSE sessions (3 sets of 5 × 5-s sprints with 25 s of passive recovery and 3 min of rest) with continuous BFR (45% arterial occlusion; excluding during between-set rest periods) or without (non-BFR). Mean and peak power output were significantly lower (p < 0.001) during BFR compared to non-BFR (d = 0.85 and 0.77, respectively). Minimum tissue saturation index during the sprints and rest periods was significantly reduced (p < 0.001) for BFR (d = 1.26 and 1.21, respectively). Electromyography root mean square was significantly decreased (p < 0.01) for biceps femoris and lateral gastrocnemius muscles during BFR (d = 0.35 and 0.79, respectively), but remained unchanged for the vastus lateralis muscle in both conditions. Oxygen consumption and minute ventilation were significantly reduced (both p < 0.01) for BFR (d = 1.46 and 0.43, respectively). Perceived limb discomfort was significantly higher (p < 0.001) for BFR (d = 0.78). No differences (p > 0.05) in blood lactate concentration or rating of perceived exertion were observed between conditions. Blood flow-restricted RSE reduced performance and likely increased the physiological and perceptual stimulus for the periphery with greater reliance on anaerobic glycolysis, despite comparable or decreased systemic demands.
Topics: Humans; Male; Cross-Over Studies; Oxygen Consumption; Young Adult; Adult; Muscle, Skeletal; Regional Blood Flow; Electromyography; Running; Athletic Performance; Perception
PubMed: 38874946
DOI: 10.1002/ejsc.12106 -
Journal of Medical Economics Jun 2024Patients with obstructive hypertrophic cardiomyopathy (oHCM) experience significant clinical burden which is associated with a high economic burden. Peak oxygen uptake... (Review)
Review
Patients with obstructive hypertrophic cardiomyopathy (oHCM) experience significant clinical burden which is associated with a high economic burden. Peak oxygen uptake (pVO2), measured by cardiopulmonary exercise testing, is used to quantify functional capacity, and has been studied as a primary endpoint in recent clinical trials. This study aimed to gather evidence to consolidate the prognostic value of pVO2 in oHCM and to assess whether it is feasible to predict health outcomes in an economic model based on changes in pVO2. A targeted literature review was conducted in MEDLINE (via PubMed) and Embase databases to identify evidence on the prognostic value of pVO2 as a surrogate health outcome to support future oHCM economic model development. Following screening, study characteristics, population characteristics and pVO2 prognostic association data were extracted. A total of 4,687 studies were identified. 3,531 and 538 studies underwent title/abstract and full-text screening, respectively, of which 151 were included and 9 of these were in hypertrophic cardiomyopathy (HCM); only 3 studies focused on oHCM. The 9 HCM studies consisted of 1 systematic literature review and 8 primary studies reporting on 27 potentially predictive relationships from a pVO2-based metric with clinical outcomes including all-cause mortality, cardiovascular mortality, sudden cardiac death, transplant, paroxysmal and permanent atrial fibrillation. pVO2 was described as a predictor of single and composite endpoints, in 3 and 6 studies respectively, with 1 study reporting on both. This study primarily uses systemic literature review methods but does not qualify as one due to not entailing parallel reviewers during title-abstract and full-text stages of review. The findings of this study suggest pVO2 is predictive of multiple health outcomes, providing rationale to use pVO2 in the development of an economic model.
PubMed: 38868944
DOI: 10.1080/13696998.2024.2367920 -
Current Developments in Nutrition Jun 2024Iron supplementation, especially in female athletes, is 1 of the influential factors in aerobic capacity, and its deficiency can lead to significant problems related to...
BACKGROUND
Iron supplementation, especially in female athletes, is 1 of the influential factors in aerobic capacity, and its deficiency can lead to significant problems related to reduced aerobic capacity.
OBJECTIVES
This study aimed to investigate the effect of 3 wk of iron supplementation on the aerobic capacity of female handball players.
METHODS
In this randomized double-blinded, and placebo control trial, 14 elite handball players (age: 21.6 ± 5.68 y; height: 169.5 ± 4.9 cm; weight: 62.2 ± 9.25 kg; body mass index (in kg/m): 21.5 ± 2.9) randomly divided into 2 supplement groups (receiving a 100 mg/d of poly-maltose tri hydroxide iron complex in the form of tablets) and the placebo group (receiving a tablet containing 100 mg/d starch which is the same color and shape as iron tablets). The supplementation protocol was performed for 3 wk during the off-season. Maximal oxygen consumption (VO), amounts of carbon dioxide at the first ventilatory threshold, amounts of carbon dioxide at the second ventilatory threshold, time to exhaustion (TTE), pulmonary ventilation (VE), ventilatory equivalents for oxygen, amounts of oxygen at the first ventilatory threshold, amounts of oxygen at the second ventilatory threshold, time to reach first ventilatory threshold, end-tidal partial pressure of oxygen at the first ventilatory threshold, end-tidal partial pressure of carbon dioxide at the first ventilatory threshold and ventilatory equivalents for carbon dioxide were measured using the Bruce test and gas analyzer in 2 pretest and posttest stages.
RESULTS
There were significant improvements in oxygen at the first ventilatory threshold, time to reach first ventilatory threshold, and end-tidal partial pressure of carbon dioxide at the first ventilatory threshold and a significant decrease in end-tidal partial pressure of oxygen at the first ventilatory threshold ( < 0.05). Also, no significant changes were found in VO, carbon dioxide at the first ventilatory threshold, carbon dioxide at the second ventilatory threshold, oxygen at the second ventilatory threshold, TTE, VE, ventilatory equivalents for oxygen, and ventilatory equivalents for carbon dioxide after 3 wk of iron supplementation ( > 0.05).
CONCLUSIONS
The study found that 3 wk of off-season iron supplementation positively impacted female handball players' aerobic capacity; however, it did not significantly improve their VO.
PubMed: 38868615
DOI: 10.1016/j.cdnut.2024.103767 -
Journal of Applied Physiology... Jun 2024Revisiting classical experiments on the impact of air resistance on metabolic rate, we aimed to overcome limitations of previous research, notably: low participant...
Revisiting classical experiments on the impact of air resistance on metabolic rate, we aimed to overcome limitations of previous research, notably: low participant numbers (n=1-3), highly turbulent wind, and confounding effects of rising body temperature. In a custom-built wind tunnel with reduced turbulence, 14 participants (8 males, 6 females) walked (5 km.h) and ran on a treadmill (70%V̇O) at 0, 2, 4 and 6 m.s headwind or tailwind in a counterbalanced design, with rest-breaks between each exposure to avoid rises in body core temperature. Oxygen consumption (V̇O) exhibited strong linear relationships versus wind direction, dynamic pressure and air speed squared(V), lower in magnitude for headwind than tailwind. A moderate linear relationship was observed between heart rate, wind direction, dynamic pressure and V. Below 4 m⸱s, the effect of wind was well within inter- and intra-individual variation and equipment uncertainty, and only at wind speeds ≥4 m⸱s did the differences in physiological responses reach statistical significance. Our data indicate that at running speeds below 4 m⸱s (14.4 km/h), indoor treadmill and outdoor running are comparable in terms of the metabolic impact of air movement relative to the person. However, this does not extend to the thermoregulatory effect of wind, with outdoor running providing a higher cooling rate due to the self-generated wind created during running. By removing the confounding impact of core temperature rises, the observed effects of headwind were lower and those of tailwind larger than observed previously. In the context of middle-distance running, headwind created by running at 21.5 km.h would result in a 2.2% increase of V̇O. A relative tailwind of the same speed would lead to a 3.1% reduction.
PubMed: 38867667
DOI: 10.1152/japplphysiol.00159.2024