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The Journal of Pharmacology and... Jun 2024Estrogen receptor (ER)-negative breast cancers are known to be aggressive and unresponsive to anti-estrogen therapy, and triple negative breast cancers are associated...
Estrogen receptor (ER)-negative breast cancers are known to be aggressive and unresponsive to anti-estrogen therapy, and triple negative breast cancers are associated with poor prognosis and metastasis. Thus, new targeted therapies are needed. FOXM1 is abundantly expressed in human cancers and implicated in protecting tumor cells from oxidative stress by reducing the levels of intracellular reactive oxygen species (ROS). Aspirin, a prototypical anti-cancer agent with deleterious side effects, has been modified to release nitric oxide and hydrogen sulfide, called NOSH-aspirin (NOSH-ASA), generating a 'safer' class of new anti-inflammatory agents. We evaluated NOSH-ASA against (ER)-negative breast cancer using cell lines and a xenograft mouse model. NOSH-ASA strongly inhibited growth of MDA-MB-231 and SKBR3 breast cancer cells with low ICs of 90{plus minus}5 and 82{plus minus}5 nM, respectively, with marginal effects on a normal breast epithelial cell line. NOSH-ASA inhibited cell proliferation, caused G/G phase arrest, increased apoptosis, and was associated with increases in ROS. In MDA-MB-231 cell xenografts, NOSH-ASA reduced tumor size markedly, which was associated with reduced proliferation (decreased PCNA expression), induction of apoptosis (increased TUNEL positive cells), and increased ROS, while NF-kB and FoxM1 that were high in untreated xenografts were significantly reduced. mRNA data for FoxM1, p21 and CyclinD1 corroborated with the respective protein expressions and arrest of cells. Taken together, these molecular events contribute to NOSH-ASA mediated growth inhibition and apoptotic death of (ER)-negative breast cells in vitro and in vivo. Additionally, as a ROS-inducer and FOXM1-inhibitor, NOSH-ASA has potential as a targeted therapy. In this investigation, we examined the cellular effects and xenograft tumor inhibitory potential of NOSH-aspirin, an NO and HS-donating hybrid, against ER-negative breast cancer, which currently lacks effective therapeutic options. The induction of reactive oxygen species and subsequent downregulation of FOXM1 represents a plausible mechanism contributing to the observed decrease in cell proliferation and concurrent increase in apoptosis. NOSH-ASA demonstrated a remarkable reduction in tumor size by 90% without inducing any observable gross toxicity, underscoring its promising translational potential.
PubMed: 38936976
DOI: 10.1124/jpet.124.002240 -
The Kobe Journal of Medical Sciences Jun 2024The fitting of oxygen mask affects the performance of it such as oxygenation or CO₂ elimination. The intersurgical EcoLite™ adult high-concentration oxygen mask... (Observational Study)
Observational Study
Oxygenation and Carbon Dioxide Rebreathing of a Well-fitting Non-rebreathing EcoLite™ Mask with a Reservoir: A Single-center Prospective Observational Study in Healthy Volunteers.
BACKGROUND
The fitting of oxygen mask affects the performance of it such as oxygenation or CO₂ elimination. The intersurgical EcoLite™ adult high-concentration oxygen mask (EcoLite with a reservoir, Intersurgical, UK) was developed to give well-fitting. The purpose of this study is to evaluate the performance of EcoLite with a reservoir compared to the conventional mask.
METHODS
Ten healthy volunteers were included in this study. EcoLite with a reservoir and conventional mask were given to patients at different oxygen flow rates (5, 8, 10, 12, and 15 L/min). Fraction of inspiratory O₂ (FO₂) and partial pressure of inspiratory CO₂ (PCO₂) were measured by a sampling tube at the middle pharynx inserted via nose.
RESULTS
The EcoLite with a reservoir had a significantly higher FO₂ than the control reservoir mask. However, the PCO₂ was significantly higher in the EcoLite with a reservoir than in the control reservoir mask, especially when the oxygen flow rate was low.
CONCLUSION
The EcoLite with a reservoir provided improved oxygenation and a better fit than the conventional reservoir masks in healthy volunteers. However, the EcoLite with a reservoir might cause higher CO₂ rebreathing at low oxygen flow rates.
Topics: Humans; Carbon Dioxide; Male; Adult; Healthy Volunteers; Masks; Prospective Studies; Female; Oxygen; Young Adult
PubMed: 38936879
DOI: 10.24546/0100489920 -
American Journal of Veterinary Research Jun 2024To describe the use of a novel wound dressing that delivers nitric oxide (NO) to naturally occurring traumatic wounds in dogs.
OBJECTIVE
To describe the use of a novel wound dressing that delivers nitric oxide (NO) to naturally occurring traumatic wounds in dogs.
ANIMALS
24 client-owned dogs with 30 wounds.
METHODS
Dogs were presented with acute traumatic wounds requiring open wound management. Wounds were bandaged with a novel NO wound dressing and reassessed as needed for continued open wound management until wounds healed by second intention or wound closure was recommended. Dogs could be removed from the study at any point at the clinician's discretion.
RESULTS
All wounds had the novel NO wound dressing used during open wound management until wound closure was recommended. Median time to wound closure was 6 days (range, 2 to 42). There were no complications directly attributed to the use of the novel wound dressing that clinically affected the dogs. Three wounds dehisced following wound closure. Wound healing was confirmed in 19 dogs with 25 wounds, with 3 dogs lost to follow-up prior to suture removal. Only 7.1% of wounds had clinical signs consistent with wound infection following wound closure.
CLINICAL RELEVANCE
The novel NO wound dressing was easy to use and well tolerated in dogs with naturally occurring traumatic wounds. It can be used throughout all phases of wound healing, simplifying open wound management.
PubMed: 38936408
DOI: 10.2460/ajvr.24.04.0124 -
Redox Biology Jun 2024The effects of low energy availability (LEA) on the immune system are poorly understood. This study examined the effects of 14 days of LEA on immune cell redox balance...
INTRODUCTION
The effects of low energy availability (LEA) on the immune system are poorly understood. This study examined the effects of 14 days of LEA on immune cell redox balance and inflammation at rest and in response to acute exercise, and exercise performance in female athletes.
METHODS
Twelve female endurance athletes (age: 26.8 ± 3.4 yrs, maximum oxygen uptake (V˙O): 55.2 ± 5.1 mL × min × kg) were included in a randomized, single-blinded crossover study. They were allocated to begin with either 14 days of optimal energy availability diet (OEA, 52 ± 2 kcal × kg fat free mass (FFM) × day) or LEA diet (22 ± 2 kcal × kg FFM × day), followed by 3 days of refueling (OEA) with maintained training volume. Peripheral blood mononuclear cells (PBMCs) were isolated, and plasma obtained at rest before and after each dietary period. The PBMCs were used for analysis of mitochondrial respiration and HO emission and specific proteins. Exercise performance was assessed on cycle by a 20-min time trial and time to exhaustion at an intensity corresponding to ∼110 % V˙O).
RESULTS
LEA was associated with a 94 % (P = 0.003) increase in PBMC NADPH oxidase 2 protein content, and a 22 % (P = 0.013) increase in systemic cortisol. LEA also caused an alteration of several inflammatory related proteins (P < 0.05). Acute exercise augmented HO emission in PBMCs (P < 0.001) following both OEA and LEA, but to a greater extent following LEA. LEA also reduced the mobilization of white blood cells with acute exercise. After LEA, performance was reduced in both exercise tests (P < 0.001), and the reduced time trial performance remained after the 3 days of refueling (P < 0.001).
CONCLUSION
14 days of LEA in female athletes increased cortisol levels and had a pronounced effect on the immune system, including increased capacity for ROS production, altered plasma inflammatory proteome and lowered exercise induced mobilization of leukocytes. Furthermore, LEA resulted in a sustained impairment in exercise performance.
PubMed: 38936255
DOI: 10.1016/j.redox.2024.103250 -
Poultry Science Jun 2024This study aimed to explore the impact of dietary Bacillus subtilis fmbj (BS) supplementation on acute intestinal dysfunction induced by lipopolysaccharide (LPS) in...
This study aimed to explore the impact of dietary Bacillus subtilis fmbj (BS) supplementation on acute intestinal dysfunction induced by lipopolysaccharide (LPS) in broilers. One hundred and eighty 1-day-old male Arbor Acres broilers were randomly divided into three treatment groups, each comprising ten replicates of 6 birds. On d 20, LPS-challenged (LPS group and LPS-BS group) and LPS-unchallenged (CON group) broilers received intraperitoneal injections of 1 mg/kg body weight LPS solution and an equivalent volume of sterile saline, respectively. Compared to the CON group, LPS disrupted (P < 0.05) the morphology of the small intestine (jejunum or ileum), exacerbated (P < 0.05) serum, small intestinal, and small intestinal mitochondrial antioxidant capacity, induced (P < 0.05) small intestinal oxidative damage, and altered (P < 0.05) the expression of genes and proteins related to antioxidants, cell adhesion, and mitochondrial function in the jejunum. The LPS-BS group exhibited a tendency towards improvement in small intestinal morphology, serum, small intestinal, and small intestinal mitochondrial antioxidant capacity, small intestinal oxidative damage, and the expression of genes and proteins related to antioxidants, cell adhesion, and mitochondrial function in the jejunum when compared to the LPS group. In conclusion, BS supplementation may confer protection against LPS-induced acute intestinal dysfunction in broilers by enhancing the activation of SIRT1/PGC1α, suggesting its potential as a valuable additive for the poultry industry.
PubMed: 38936217
DOI: 10.1016/j.psj.2024.103964 -
PloS One 2024Geotextiles are excellent anti-filtration materials commonly used in the field of water conservancy engineering; however, the factors affecting the water permeability...
Geotextiles are excellent anti-filtration materials commonly used in the field of water conservancy engineering; however, the factors affecting the water permeability performance of geotextiles under stressed states during operation have not been fully identified. To investigate the effect of unidirectional stretching on the water permeability of geotextiles, a unidirectional rheological head infiltration test was conducted on the geotextiles using a self-developed test apparatus. In addition, the water permeability of geotextiles with different thicknesses and tensile states was calculated using a set of water permeability calculation methods based on the nonlaminar flow state of geotextiles. The results showed that the water permeability of the W120 geotextile samples initially decreased and then increased under warp stretching and gradually increased under weft stretching. However, the water permeability of the W200 geotextile samples initially decreased and then increased under both warp and weft stretching. Therefore, the thickness of the geotextile affected its permeability properties.
Topics: Permeability; Water; Tensile Strength; Rheology; Materials Testing
PubMed: 38935683
DOI: 10.1371/journal.pone.0306057 -
PloS One 2024Aluminum (Al) toxicity is an important factor restricting the normal growth of plants in acidic soil. Rhododendron (Ericaceae) can grow relatively well in acidic soil....
Aluminum (Al) toxicity is an important factor restricting the normal growth of plants in acidic soil. Rhododendron (Ericaceae) can grow relatively well in acidic soil. To uncover the adaptive mechanisms of photosynthesis under Al stress, the influence of Al stress on the photosynthetic activities of Al-sensitive (Baijinpao) and Al-resistant (Kangnaixin) rhododendron cultivars was examined by measuring gas exchange, chlorophyll fluorescence, and the modulated reflection of light at 820 nm. Under Al stress conditions, the net photosynthetic rate and stomatal conductance of the rhododendron leaves decreased, whereas the intercellular CO2 concentration increased. The Al stress treatment damaged the oxygen-evolving complex of the rhododendron seedlings, while also inhibiting electron transport on the photosystem II (PSII) donor side. In addition, the exposure to Al stress restricted the oxidation of plastocyanin (PC) and the photosystem I (PSI) reaction center (P700) and led to the re-reduction of PC+ and P700+. The comparison with Kangnaixin revealed an increase in the PSII connectivity in Baijinpao. Additionally, the donor-side electron transport efficiency was more inhibited and the overall activity of PSII, PSI, and the intersystem electron transport chain decreased more extensively in Baijinpao than in Kangnaixin. On the basis of the study findings, we concluded that Al stress adversely affects photosynthesis in rhododendron seedlings by significantly decreasing the activity of PSII and PSI. Under Al stress, Kangnaixin showed stronger tolerance compared with Baijinpao.
Topics: Rhododendron; Aluminum; Chlorophyll; Photosynthesis; Fluorescence; Photosystem II Protein Complex; Stress, Physiological; Plant Leaves; Electron Transport; Light; Photosystem I Protein Complex
PubMed: 38935623
DOI: 10.1371/journal.pone.0305133 -
Cell Reports Jun 2024Circadian rhythms are internal biological rhythms driving temporal tissue-specific, metabolic programs. Loss of the circadian transcription factor BMAL1 in the...
Circadian rhythms are internal biological rhythms driving temporal tissue-specific, metabolic programs. Loss of the circadian transcription factor BMAL1 in the paraventricular nucleus (PVN) of the hypothalamus reveals its importance in metabolic rhythms, but its functions in individual PVN cells are poorly understood. Here, loss of BMAL1 in the PVN results in arrhythmicity of processes controlling energy balance and alters peripheral diurnal gene expression. BMAL1 chromatin immunoprecipitation sequencing (ChIP-seq) and single-nucleus RNA sequencing (snRNA-seq) reveal its temporal regulation of target genes, including oxytocin (OXT), and restoring circulating OXT peaks in BMAL1-PVN knockout (KO) mice rescues absent activity rhythms. While glutamatergic neurons undergo day/night changes in expression of genes involved in cell morphogenesis, astrocytes and oligodendrocytes show gene expression changes in cytoskeletal organization and oxidative phosphorylation. Collectively, our findings show diurnal gene regulation in neuronal and non-neuronal PVN cells and that BMAL1 contributes to diurnal OXT secretion, which is important for systemic diurnal rhythms.
PubMed: 38935503
DOI: 10.1016/j.celrep.2024.114380 -
Journal of the American Heart... Jun 2024Wild-type transthyretin amyloid (ATTRwt) cardiomyopathy is increasingly recognized in the development of heart failure. The link between cardiac performance,...
BACKGROUND
Wild-type transthyretin amyloid (ATTRwt) cardiomyopathy is increasingly recognized in the development of heart failure. The link between cardiac performance, hemodynamics, and mitochondrial function in disease stages of ATTRwt has not previously been studied but may provide new insights into the pathophysiology and clinical performance of the patients.
METHODS AND RESULTS
The study investigated 47 patients diagnosed with ATTRwt at Aarhus University Hospital, Denmark. Patients were stratified according to the disease stages of the National Amyloidosis Centre (NAC) as NAC I with low levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) (NAC I-L, n=14), NAC I with high levels NT-proBNP (NAC I-H, n=20), and NAC II-III (n=13). Exercise testing with simultaneous right heart catheterization was performed in all patients. Endomyocardial biopsies were collected from the patients and the mitochondrial oxidative phosphorylation capacity was assessed. All NAC disease groups, even in the NAC I-L group, a significant abnormal increase in biventricular filling pressures were noted during exercise while the filling pressures was normal or near normal at rest. The inotropic response to exercise was reduced with diminished increase in cardiac output which was significantly more pronounced in the NAC I-H (Diff. -2.4, 95% CI (-4.2: -0.7), =0.00) and the NAC II-III group (Diff: -3.1 L/min, 95% CI (-5.2: -1.1), =0.00) compared with the NAC I-L group. The pulmonary artery wedge pressure to cardiac output ratio at peak exercise was significantly different between NAC I-L and NAC II-III (Diff: 1.6 mm Hg*min/L, 95% CI (0.01:3.3, =0.04)). Patients with ATTRwt had a reduced oxidative phosphorylation capacity which correlated to left ventricular mass but not to cardiac output capacity.
CONCLUSIONS
An abnormal restrictive left ventricle and right ventricle response to exercise was demonstrated, even present in patients with early-stage ATTRwt. In more advanced disease stages a progressive impairment of the pressure-flow relationship was noted. The myocyte energetics is deranged but not associated to the contractile reserve or restrictive filling characteristics in ATTRwt.
PubMed: 38934860
DOI: 10.1161/JAHA.124.034213 -
Indian Journal of Public Health Oct 2023LAMP assay is widely used for detecting pathogens. We observed that the conventional and gradient polymerase chain reaction (PCR) could not detect the extracted...
Electrophoresis of Amplicons is a Better Method to Understand the Performance of Loop-mediated Isothermal Amplification Assay for Screening the Presence of Escherichia coli in Water.
LAMP assay is widely used for detecting pathogens. We observed that the conventional and gradient polymerase chain reaction (PCR) could not detect the extracted Escherichia coli DNA; real-time PCR was able to detect up to a certain limit (10-8 bacterial dilution). At the same time, the LAMP assay could detect the bacteria at a much lower concentration (10-14 dilution). The results of the LAMP assay were evaluated using agarose gel electrophoresis and DNA binding dye (PicoGreen), but only gel electrophoresis gave reliable results. Therefore, we propose using electrophoresis-based amplicon detection to overcome the limitations of dye-based detection. We believe that this amplicon detection will go a long way in the screening of potable drinking water.
Topics: Escherichia coli; Nucleic Acid Amplification Techniques; Water Microbiology; Real-Time Polymerase Chain Reaction; Humans; Electrophoresis, Agar Gel; DNA, Bacterial; Molecular Diagnostic Techniques; Drinking Water
PubMed: 38934812
DOI: 10.4103/ijph.ijph_1628_22