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Cancer Biology & Therapy Dec 2024Chronic stress can induce stress-related hormones; norepinephrine (NE) is considered to have the highest potential in cancer. NE can stimulate the expression of...
BACKGROUND
Chronic stress can induce stress-related hormones; norepinephrine (NE) is considered to have the highest potential in cancer. NE can stimulate the expression of hypoxia-inducible factor-1α (HIF-1α), which is associated with vascular endothelial growth factor (VEGF) secretion and tumor angiogenesis. However, the underlying mechanisms are poorly understood.
METHODS
Tumor-bearing mice were subjected to chronic restraint stress and treated with normal saline, human monoclonal VEGF-A neutralizing antibody bevacizumab, or β-adrenergic receptor (β-AR) antagonist (propranolol). Tumor growth and vessel density were also evaluated. Human colorectal adenocarcinoma cells were treated with NE, propranolol, or the inhibitor of transforming growth factor-β (TGF-β) receptor Type I kinase (Ly2157299) . TGF-β1 in mouse serum and cell culture supernatants was quantified using ELISA. The expression of HIF-1α was measured using Real time-PCR and western blotting. Cell migration and invasion were tested.
RESULTS
Chronic restraint stress attenuated the efficacy of bevacizumab and promoted tumor growth and angiogenesis in a colorectal tumor model. Propranolol blocked this effect and inhibited TGF-β1 elevation caused by chronic restraint stress or NE. NE upregulated HIF-1α expression, which was reversed by propranolol or Ly2157299. Propranolol and Ly2157199 blocked NE-stimulated cancer cell migration and invasion.
CONCLUSIONS
Our results demonstrate the effect of NE on tumor angiogenesis and the critical role of TGF-β1 signaling during this process. In addition, β-AR/TGF-β1 signaling/HIF-1α/VEGF is a potential signaling pathway. This study also indicates that psychosocial stress might be a risk factor which weakens the efficacy of anti-angiogenic therapy.
Topics: Animals; Colorectal Neoplasms; Humans; Neovascularization, Pathologic; Mice; Transforming Growth Factor beta1; Hypoxia-Inducible Factor 1, alpha Subunit; Signal Transduction; Bevacizumab; Propranolol; Cell Line, Tumor; Vascular Endothelial Growth Factor A; Male; Cell Movement; Norepinephrine; Stress, Psychological; Adrenergic beta-Antagonists; Angiogenesis; Pyrazoles; Quinolines
PubMed: 38857055
DOI: 10.1080/15384047.2024.2366451 -
Journal of the Science of Food and... Jun 2024Traditional sun-drying aquatic products are popular and recognized by customers, owing to their unique flavor and long-term preservation. However, the product quality...
BACKGROUND
Traditional sun-drying aquatic products are popular and recognized by customers, owing to their unique flavor and long-term preservation. However, the product quality and production efficiency cannot be guaranteed. Cololabis saira is rich in unsaturated fatty acids, which are susceptible to hyperoxidation during the drying process. This study aimed to make clear the role of ultraviolet (UV) radiation in flavor formation during drying processes of Cololabis saira to develop a modern drying technology.
RESULTS
Lipid oxidation analysis revealed that moderate hydrolytic oxidation occurred in the UV-assisted cold-air drying group due to the combined influence of UV and cold-air circulation, resulting in the thiobarbituric acid reactive substances value being higher than that of cold-air drying group but lower than the natural drying group. Hexanal, heptanal, cis-4-heptenal, octanal, nonanal, (trans,trans)-2,4-heptadienal, (trans,trans)-2,6-nonanedial, 1-octen-3-ol, heptanol, 2,3-pentanedione, 3,5-octadien-2-one and trimethylamine were identified as the characteristic flavor odor-active compounds present in all Cololabis saira samples. Yet, during the natural drying process, sunlight promoted the lipid oxidation, resulting in the highest degree of lipid oxidation among three drying methods. Light and heat promoted lipid oxidation in Cololabis saira prepared through natural drying process, leading to a large accumulation of volatile compounds, such as 3-methylbutyraldehyde, 2,3-pentanedione, 1-propanol, and 3-pentanone. Cold air circulation inhibited lipid oxidation to some extent, resulting in a blander flavor profile. More cis-4-heptenal, cis-2-heptenal, octanal and 2-ethylfuran accumulated during the UV-assisted cold-air drying process, enriching its greasy flavor and burnt flavor.
CONCLUSION
UV-assisted cold-air drying could promote moderate lipid oxidation, which is beneficial for improving product flavor. To sum up, UV radiation played a crucial role in the flavor formation during the drying process of Cololabis saira. © 2024 Society of Chemical Industry.
PubMed: 38856111
DOI: 10.1002/jsfa.13640 -
JBJS Case Connector Apr 2024We report a case of an intramuscular thigh hemangioma in a 19-year-old woman with a several year history of atraumatic thigh pain. Radiographs obtained by her primary...
CASE
We report a case of an intramuscular thigh hemangioma in a 19-year-old woman with a several year history of atraumatic thigh pain. Radiographs obtained by her primary care physician demonstrated periosteal bone reaction, prompting referral to Orthopaedic Oncology department. The patient had successful symptomatic management with propranolol.
CONCLUSION
The case highlights the diagnosis and potential treatments. In a stepwise approach to care for symptomatic benign vascular lesions, propranolol has been a proven therapeutic option and may be a useful first-line therapy for symptomatic hemangiomas.
Topics: Humans; Female; Thigh; Hemangioma; Young Adult; Muscle Neoplasms; Propranolol; Radiography; Adrenergic beta-Antagonists
PubMed: 38848412
DOI: 10.2106/JBJS.CC.24.00060 -
Chemical Science Jun 2024Growing polymers inside porous metal-organic frameworks (MOFs) can allow incoming guests to access the backbone of otherwise non-porous polymers, boosting the number...
Growing polymers inside porous metal-organic frameworks (MOFs) can allow incoming guests to access the backbone of otherwise non-porous polymers, boosting the number and/or strength of available adsorption sites inside the porous support. In the present work, we have devised a novel post-synthetic modification (PSM) strategy that allows one to graft metal-chelating functionality onto a polymer backbone while inside MOF pores, enhancing the material's ability to recover Pt(iv) from complex liquids. For this, polydopamine (PDA) was first grown inside of a MOF, known as Fe-BTC (or MIL-100 Fe). Next, a small thiol-containing molecule, 2,3-dimercapto-1-propanol (DIP), was grafted to the PDA a Michael addition. After the modification of the PDA, the Pt adsorption capacity and selectivity were greatly enhanced, particularly in the low concentration regime, due to the high affinity of the thiols towards Pt. Moreover, the modified composite was found to be highly selective for precious metals (Pt, Pd, and Au) over common base metals found in electronic waste (, Pb, Cu, Ni, and Zn). X-ray photoelectron spectroscopy (XPS) and X-ray absorption spectroscopy (XAS) provided insight into the Pt adsorption/reduction process. Last, the PSM was extended to various thiols to demonstrate the versatility of the chemistry. It is hoped that this work will open pathways for the future design of novel adsorbents that are fine-tuned for the rapid, selective retrieval of high-value and/or critical metals from complex liquids.
PubMed: 38846398
DOI: 10.1039/d4sc00174e -
Langmuir : the ACS Journal of Surfaces... Jun 2024The nucleation mechanism of bulk nanobubbles remains unclear despite the considerable attention they have received in recent years. We propose two hypotheses: (i) The...
The nucleation mechanism of bulk nanobubbles remains unclear despite the considerable attention they have received in recent years. We propose two hypotheses: (i) The gas supersaturation in the bulk liquid is the primary factor for nanobubble nucleation, and (ii) the mixing of the same solvent at varying gas solubilities should produce nanobubbles, provided that the first hypothesis is correct. To test this hypothesis, we performed extensive experiments on nanobubble nucleation in both water and organic solvents. The temperature difference between hot and cold samples ranged from 10 to 80 °C in pure solvents such as water, methanol, ethanol, propanol, and butanol prepared and mixed in equal proportions. To the best of our knowledge, we report bulk nanobubble nucleation by mixing hot and cold solvents for the first time. The refractive index value calculations using Mie scattering theory confirmed the existence of nanobubbles. When surface tension dominates over surface charge, the critical work for nanobubble formation is ∝ 1/ξ, and when surface charge dominates over surface tension, the critical work is ∝ ξ. Our experimental results verify such dependency by measuring nanobubbles nucleated with varying degrees of gas supersaturation.
PubMed: 38845184
DOI: 10.1021/acs.langmuir.4c01358 -
Journal of Controlled Release :... Jul 2024The use of animal experiments can be minimized with computational models capable of reflecting the simulated environments. One such environment is intestinal fluid and...
The use of animal experiments can be minimized with computational models capable of reflecting the simulated environments. One such environment is intestinal fluid and the colloids formed in it. In this study we used molecular dynamics simulations to investigate solubilization patterns for three model drugs (carvedilol, felodipine and probucol) in dog intestinal fluid, a lipid-based formulation, and a mixture of both. We observed morphological transformations that lipids undergo due to the digestion process in the intestinal environment. Further, we evaluated the effect of bile salt concentration and observed the importance of interindividual variability. We applied two methods of estimating solubility enhancement based on the simulated data, of which one was in good qualitative agreement with the experimentally observed solubility enhancement. In addition to the computational simulations, we also measured solubility in i) aspirated dog intestinal fluid samples and ii) simulated canine intestinal fluid in the fasted state, and found there was no statistical difference between the two. Hence, a simplified dissolution medium suitable for in vitro studies provided physiologically relevant data for the systems explored. The computational protocol used in this study, coupled with in vitro studies using simulated intestinal fluids, can serve as a useful prescreening tool in the process of drug delivery strategies development.
Topics: Dogs; Animals; Solubility; Molecular Dynamics Simulation; Felodipine; Probucol; Carvedilol; Lipids; Body Fluids; Bile Acids and Salts; Male; Intestinal Secretions
PubMed: 38844179
DOI: 10.1016/j.jconrel.2024.06.008 -
Biological & Pharmaceutical Bulletin 2024This study aimed to validate the In vitro Dissolution Absorption System 2 (IDAS2) containing a biological barrier of Caco-2 or Madin-Darby canine kidney (MDCK) cell...
This study aimed to validate the In vitro Dissolution Absorption System 2 (IDAS2) containing a biological barrier of Caco-2 or Madin-Darby canine kidney (MDCK) cell monolayer through dose sensitivity studies. Metoprolol and propranolol were selected as Biopharmaceutics Classification System (BCS) Class I model drugs, and atenolol as a Class III model drug. The IDAS2 is comprised of a dissolution vessel (500 mL) and two permeation chambers (2 × 8.0 mL) mounted with Caco-2 or MDCK cell monolayer. One or two immediate-release tablet(s) of the model drug were added to the dissolution vessel, and the time profiles of dissolution and permeation were observed. Greater than 85% of metoprolol and propranolol (tested at two dosing concentrations) were dissolved by 15 min, and all drugs were fully dissolved by 30 min. All three drugs were more permeable across Caco-2 cells than MDCK cells with a linear increase in permeation across both cells at both dose concentrations. Thus, the dose sensitivity of the IDAS2 was demonstrated using both cell barriers. These results indicate a successful qualification of IDAS2 for the development/optimization of oral formulations and that MDCK cells can be utilized as a surrogate for Caco-2 cells.
Topics: Dogs; Caco-2 Cells; Humans; Animals; Madin Darby Canine Kidney Cells; Propranolol; Metoprolol; Atenolol; Solubility; Dose-Response Relationship, Drug; Biopharmaceutics; Permeability; Intestinal Absorption
PubMed: 38839364
DOI: 10.1248/bpb.b24-00150 -
Journal of Molecular Graphics &... May 2024Aiming at shedding light on the molecular interactions in deep eutectic solvents (DESs), the DESs based on tetrabutylammonium bromide (TBAB) as hydrogen bond acceptor...
Aiming at shedding light on the molecular interactions in deep eutectic solvents (DESs), the DESs based on tetrabutylammonium bromide (TBAB) as hydrogen bond acceptor (HBA) and carboxylic acids (CAs) (formic acid (FA), oxalic acid (OA), and malonic acid (MA)) as hydrogen bond donor (HBD) were investigated by both experimental and theoretical techniques. The thermal behaviors of the prepared DESs were investigated by differential scanning calorimetry (DSC) method. In order to study the hydrogen bond formation between the DESs constituents, the FT-IR analysis was carried out. The large positive deviations of the iso solvent activity lines of ternary HBA + HBD + 2-propanol mixtures determined by the isopiestic technique from the semi-ideal behavior indicate that CAs interact strongly with TBAB and therefore they can form DESs. Molecular dynamics (MD) simulations were performed to present an atomic-scale image of the components and describe the microstructure of DESs. From the MD simulations, the radial distribution functions (RDFs), coordination numbers (CNs), combined distribution functions (CDFs), and spatial distribution functions (SDFs) were calculated to investigate the interaction between the components and three-dimensional visualization of the DESs. The obtained results confirmed the importance of hydrogen bonds in the formation of TBAB/CAs DESs.
PubMed: 38838616
DOI: 10.1016/j.jmgm.2024.108805 -
Spectrochimica Acta. Part A, Molecular... Oct 2024The photophysical properties of conformationally flexible (TPA-C) and partially rigidified (Cz-C) triarylamine acids were explored in solid as well as solution state and...
The photophysical properties of conformationally flexible (TPA-C) and partially rigidified (Cz-C) triarylamine acids were explored in solid as well as solution state and correlated with the structure. TPA-C and Cz-C exhibited moderate solid-state fluorescence (Φ = 6.2 % (TPA-C) and 5.6 % (Cz-C)) and self-reversible mechanofluorochromism. TPA-C produced fluorescent polymorphs (TPA-C-1 and TPA-C-2) with tunable fluorescence. TPA-C-1 showed unusual carboxylic acid intermolecular interactions whereas TPA-C-2 and Cz-C showed usual carboxylic acid dimer. TPA-C exhibited strong solvent polarity dependent tunable fluorescence (Φ = 0.01 to 0.11 compared to quinine sulphate standard) but Cz-C was non-emissive in the solution state. The dual emissive TPA-C showed highly sensitive fluorescence changes in organic solvents (CHCN, THF, DMF, EtOH) when trace amount of water was added. In CHCN, TPA-C showed weak fluorescence at 474 nm and addition of water (1 %) exhibited significant blue shift (λ = 416 nm). The fluorescence intensity was gradually decreased with blue shifting in DMF, THF and EtOH with water addition. Importantly, TPA-C showed drastically different fluorescence in n-propanol (n-PA) and iso-propanol (IPA). TPA-C in n-PA showed fluorescence at 408 nm that was clearly red shifted to 438 nm with 0.1 % addition of IPA. The limit of detection (LOD) of water in CHCN, DMF, THF and EtOH by TPA-C revealed 0.02, 0.7, 0.08 and 0.77 %, respectively. The LOD of IPA sensing in n-PA is 0.05 % and indicated the very efficient sensing and distinguishing propanol isomers. Thus, simple triphenylamine acid showed excellent water sensing and propanol isomers discrimination that could be attributed to the twisted intramolecular charge transfer (TICT) formation.
PubMed: 38830332
DOI: 10.1016/j.saa.2024.124557 -
Environmental Science and Pollution... Jun 2024Solvent-based CO capture is a commonly employed post-combustion technique in processes involving absorber-stripper columns. This study focused on computer simulations...
Solvent-based CO capture is a commonly employed post-combustion technique in processes involving absorber-stripper columns. This study focused on computer simulations with equilibrium- and rate-based modeling of CO capture using the amine solvents 2-amino-2-methyl-1-propanol (AMP), diethanolamine (DEA), and methyl diethanolamine (MDEA) and thermodynamic methods involving electrolyte NRTL models. The objective of this study was to understand the impacts of rate-based modeling, the type of amine, and thermodynamic methods on carbon capture. Within this study, the amine-based CO capture process from coal-power plant flue gas was studied using Aspen Plus modeling. Simulations were also conducted to determine the impact of thermodynamics and kinetics on the CO capture performance of the system. The results were analyzed on the basis of captured CO according to the solvents and models. The equilibrium approach was mostly invalid because of the oversimplified ideal stage assumptions through the column. The lowest carbon capture capacity was obtained with MDEA, while DEA yielded the best results. A sensitivity analysis with rate-based modeling showed the significant impact of the inlet CO composition. The amine-based CO capture process simulation included solution chemistry, electrolyte thermodynamics, rigorous transport property modeling, reaction kinetics, and rate-based multistage simulation, which could be applicable to different solvent systems.
Topics: Carbon Dioxide; Thermodynamics; Kinetics; Amines; Carbon
PubMed: 38816632
DOI: 10.1007/s11356-024-33792-y