-
Chemistry (Weinheim An Der Bergstrasse,... Feb 2020Pulsed laser irradiation of solid potassium cyanide (KCN) produces, besides free nitrogen and carbon atoms, the molecular species KN and KC which are potential...
Pulsed laser irradiation of solid potassium cyanide (KCN) produces, besides free nitrogen and carbon atoms, the molecular species KN and KC which are potential candidates for interstellar species of potassium. Additionally, N , N , KN , C , C , and KC are produced and isolated in solid noble gases as well as in solid N . Molecular potassium nitrene (KN) reacts with dinitrogen in neon and argon matrices after photochemical excitation (λ=470 nm) forming molecular end-on (C ) and side-on (C ) potassium azide isomers. The side-on isomer (C ) is thermodynamically favored at the CCSD(T)/ma-def2-TZVP level of theory. It can be obtained from the end-on isomer by UV-irradiation (λ=273 nm).
PubMed: 31721339
DOI: 10.1002/chem.201905103 -
The European Journal of Neuroscience Feb 2020Hippocampus is a limbic structure involved in the baroreflex and chemoreflex control that receives extensive cholinergic input from basal forebrain. Hippocampal...
Hippocampus is a limbic structure involved in the baroreflex and chemoreflex control that receives extensive cholinergic input from basal forebrain. Hippocampal muscarinic receptors activation by acetylcholine might evoke nitric oxide synthesis, which is an important neuromodulator of cardiovascular responses. Thus, we hypothesize that cholinergic and nitrergic neurotransmission within the DH modulates the baroreflex and chemoreflex function. We have used vasoactive drugs (phenylephrine and sodium nitroprusside), and potassium cyanide infused peripherally to induce, respectively, baroreflex or chemoreflex responses in awake animals. Bilateral injection into the DH of the acetylcholinesterase inhibitor (neostigmine) reduced baroreflex responses. Meanwhile, the non-selective muscarinic receptor antagonist (atropine) or the M1-selective muscarinic receptor antagonist increased baroreflex responses (pirenzepine). Furthermore, the neuronal nitric oxide synthase inhibitor (N-propyl) or the intracellular NO scavenger (carboxy-PTIO) increased baroreflex responses, as well as the selective inhibitor of NO-sensitive guanylyl cyclase (ODQ), increased the baroreflex responses. Besides, bilateral administration of an ineffective dose of a neuronal nitric oxide synthase inhibitor abolished the reduction in the baroreflex responses evoked by an acetylcholinesterase inhibitor. On the other hand, we have demonstrated that hippocampal cholinergic neurotransmission did not influence the chemoreflex function. Taken together, our findings suggest that nNOS-derived nitric oxide in the DH participates in acetylcholine-evoked baroreflex responses.
Topics: Animals; Baroreflex; Cholinergic Agents; Hippocampus; Nitric Oxide; Rats; Rats, Wistar; Synaptic Transmission
PubMed: 31626713
DOI: 10.1111/ejn.14599 -
Acta Physiologica (Oxford, England) Aug 2022Stimulation of peripheral chemoreceptors, as during hypoxia, increases breathing and respiratory-related sympathetic bursting. Activation of catecholaminergic C1...
AIMS
Stimulation of peripheral chemoreceptors, as during hypoxia, increases breathing and respiratory-related sympathetic bursting. Activation of catecholaminergic C1 neurones induces sympathoexcitation, while its ablation reduces the chemoreflex sympathoexcitatory response. However, no study has determined the respiratory phase(s) in which the pre-sympathetic C1 neurones are recruited by peripheral chemoreceptor and whether C1 neurone activation affects all phases of respiratory modulation of sympathetic activity. We addressed these unknowns by testing the hypothesis that peripheral chemoreceptor activation excites pre-sympathetic C1 neurones during inspiration and expiration.
METHODS
Using the in situ preparation of rat, we made intracellular recordings from baroreceptive pre-sympathetic C1 neurones during peripheral chemoreflex stimulation. We optogenetically activated C1 neurones selectively and compared any respiratory-phase-related increases in sympathetic activity with that which occurs following stimulation of the peripheral chemoreflex.
RESULTS
Activation of peripheral chemoreceptors using cytotoxic hypoxia (potassium cyanide) increased the firing frequency of C1 neurones and both the frequency and amplitude of their excitatory post-synaptic currents during the phase of expiration only. In contrast, optogenetic stimulation of C1 neurones activates inspiratory neurones, which secondarily inhibit expiratory neurones, but produced comparable increases in sympathetic activity across all phases of respiration.
CONCLUSION
Our data reveal that the peripheral chemoreceptor-mediated expiratory-related sympathoexcitation is mediated through excitation of expiratory neurones antecedent to C1 pre-sympathetic neurones; these may be found in the Kölliker-Fuse nucleus. Despite peripheral chemoreceptor excitation of inspiratory neurones, these do not trigger C1 neurone-mediated increases in sympathetic activity. These studies provide compelling novel insights into the functional organization of respiratory-sympathetic neural networks.
Topics: Animals; Chemoreceptor Cells; Exhalation; Hypoxia; Medulla Oblongata; Rats; Respiration; Sympathetic Nervous System
PubMed: 35722749
DOI: 10.1111/apha.13853 -
International Journal of Biological... May 2021Superoxide dismutases are the enzymes involved in dismutation of superoxide radicals into oxygen and hydrogen peroxide. The present work reports a thermostable Fe/Mn SOD...
Superoxide dismutases are the enzymes involved in dismutation of superoxide radicals into oxygen and hydrogen peroxide. The present work reports a thermostable Fe/Mn SOD of Geobacillus sp. strain PCH100 (GsSOD) isolated from glacial soil. Purified recombinant GsSOD is a dimeric protein of ~57 kDa that exhibited highest activity at a temperature of 10 °C and pH of 7.8. Maximum enzyme velocity and Michaelis constant of the GsSOD were 1098.90 units/mg and 0.62 μM, respectively. At 80 °C, thermal inactivation rate constant and half-life of GsSOD were 3.33 × 10 min and 208 min, respectively. Interestingly, GsSOD tolerated a temperature of 100 °C and 130 °C up to 15 min and 5 min, respectively. Circular dichroism and differential scanning calorimetry confirmed thermostable nature of GsSOD. Apoenzyme of GsSOD regained enzymatic activity in the presence of Fe and Mn as metal ion cofactors. GsSOD was stable under varying concentrations of chemicals, namely ethylenediaminetetraacetic acid, potassium cyanide, hydrogen peroxide, chloroform-ethanol, 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate, Tween-20, Triton X-100, urea, and guanidine hydrochloride. The enzyme exhibited >70% activity in presence of 10 mM metal ions. Owing to its thermostable nature and resistance to chemical inhibitors, GsSOD is a potential enzyme for industrial applications.
Topics: Bacterial Proteins; Enzyme Stability; Geobacillus; Hydrogen-Ion Concentration; India; Kinetics; Soil Microbiology; Superoxide Dismutase; Temperature
PubMed: 33676984
DOI: 10.1016/j.ijbiomac.2021.03.019 -
Hypertension (Dallas, Tex. : 1979) Nov 2020The carotid body is implicated as an important mediator and potential treatment target for hypertension. The mechanisms driving increased carotid body tonicity in...
The carotid body is implicated as an important mediator and potential treatment target for hypertension. The mechanisms driving increased carotid body tonicity in hypertension are incompletely understood. Using a large preclinical animal model, which is crucial for translation, we hypothesized that carotid sinus nerve denervation would chronically decrease blood pressure in a renovascular ovine model of hypertension in which hypertonicity of the carotid body is associated with reduced common carotid artery blood flow. Adult ewes underwent either unilateral renal artery clipping or sham surgery. Two weeks later, flow probes were placed around the contralateral renal and common carotid arteries. Hypertension was accompanied by a significant reduction in common carotid blood flow but no change in renal blood flow. Carotid sinus nerve denervation significantly reduced blood pressure compared with sham. In both hypertensive and normotensive animals, carotid body stimulation using potassium cyanide caused dose-dependent increases in mean arterial pressure and common carotid conductance but a reduction in renal vascular conductance. These responses were not different between the animal groups. Taken together, our findings indicate that (1) the carotid body is activated in renovascular hypertension, and this is associated with reduced blood flow (decreased vascular conductance) in the common carotid artery and (2) the carotid body can differentially regulate blood flow to the common carotid and renal arteries. We suggest that in the ovine renovascular model, carotid body hypertonicity may be a product of reduced common carotid artery blood flow and plays an amplifying role with the kidney in the development of hypertension.
Topics: Animals; Blood Pressure; Carotid Artery, Common; Carotid Body; Disease Models, Animal; Hypertension, Renovascular; Kidney; Regional Blood Flow; Renal Artery; Sheep; Sympathetic Nervous System
PubMed: 32981362
DOI: 10.1161/HYPERTENSIONAHA.120.15676 -
Frontiers in Physiology 2020In ventricular myocytes, spontaneous release of calcium (Ca) from the sarcoplasmic reticulum via ryanodine receptors ("Ca sparks") is acutely increased by stretch, due...
In ventricular myocytes, spontaneous release of calcium (Ca) from the sarcoplasmic reticulum via ryanodine receptors ("Ca sparks") is acutely increased by stretch, due to a stretch-induced increase of reactive oxygen species (ROS). In acute regional ischemia there is stretch of ischemic tissue, along with an increase in Ca spark rate and ROS production, each of which has been implicated in arrhythmogenesis. Yet, whether there is an impact of ischemia on the stretch-induced increase in Ca sparks and ROS has not been investigated. We hypothesized that ischemia would enhance the increase of Ca sparks and ROS that occurs with stretch. Isolated ventricular myocytes from mice (male, C57BL/6J) were loaded with fluorescent dye to detect Ca sparks (4.6 μM Fluo-4, 10 min) or ROS (1 μM DCF, 20 min), exposed to normal Tyrode (NT) or simulated ischemia (SI) solution (hyperkalemia [15 mM potassium], acidosis [6.5 pH], and metabolic inhibition [1 mM sodium cyanide, 20 mM 2-deoxyglucose]), and subjected to sustained stretch by the carbon fiber technique (~10% increase in sarcomere length, 15 s). Ca spark rate and rate of ROS production were measured by confocal microscopy. Baseline Ca spark rate was greater in SI (2.54 ± 0.11 sparks·s·100 μm; = 103 cells, = 10 mice) than NT (0.29 ± 0.05 sparks·s·100 μm; = 33 cells, = 9 mice; < 0.0001). Stretch resulted in an acute increase in Ca spark rate in both SI (3.03 ± 0.13 sparks·s·100 μm; < 0.0001) and NT (0.49 ± 0.07 sparks·s·100 μm; < 0.0001), with the increase in SI being greater than NT (+0.49 ± 0.04 vs. +0.20 ± 0.04 sparks·s·100 μm; < 0.0001). Baseline rate of ROS production was also greater in SI (1.01 ± 0.01 normalized slope; = 11, = 8 mice) than NT (0.98 ± 0.01 normalized slope; = 12, = 4 mice; < 0.05), but there was an acute increase with stretch only in SI (+12.5 ± 2.6%; < 0.001). Ischemia enhances the stretch-induced increase of Ca sparks in ventricular myocytes, with an associated enhancement of stretch-induced ROS production. This effect may be important for premature excitation and/or in the development of an arrhythmogenic substrate in acute regional ischemia.
PubMed: 32372969
DOI: 10.3389/fphys.2020.00289 -
Plant Disease Oct 2022As the excessive use of chemical fertilizers harms organisms and adversely affects the soil environment, the replacement of chemical fertilizers with biological...
As the excessive use of chemical fertilizers harms organisms and adversely affects the soil environment, the replacement of chemical fertilizers with biological fertilizers has attracted widespread attention as an environmental protection strategy. In this study, the effects of rhizosphere bacteria inoculation on growth of var. seedlings, soil parameters, soil microbial community structure, and the biocontrol of damping-off were studied by pot experiments. The results showed that all three rhizosphere bacteria (, , and A07) tested exhibited growth-promoting properties, such as the production of indole-3-acetic acid, hydrolase, siderophores, and hydrogen cyanide; nitrogen fixation; and phosphorus solubilization. The application of the three bacteria increased plant biomass, root structure, and nutrient content and also increased soil nutrient content and enzyme activity. Bacterial inoculation promoted the growth of beneficial bacteria and antagonistic bacteria by adjusting the physicochemical properties of the soil, thereby improving the bacterial community structure. Among the soil features, available nitrogen, total nitrogen, available potassium, and urease activity were the main influencing factors. In addition, it was also found that bacterial inoculation significantly increased the activities of plant superoxide dismutase, catalase, peroxidase, and other defense enzymes; enhanced plant disease resistance; effectively inhibited damping-off; and promoted plant growth. In summary, the application of three rhizosphere bacteria systematically affected the interaction between plants, soil parameters, and soil microbial communities. These results provide a basis for understanding how rhizosphere bacteria promote the growth of var. , thereby offering a promising sustainable alternative to chemical fertilizers.
Topics: Bacteria; Catalase; Fertilizers; Hydrogen Cyanide; Microbiota; Nitrogen; Phosphorus; Pinus sylvestris; Potassium; Rhizoctonia; Seedlings; Siderophores; Soil; Superoxide Dismutase; Urease
PubMed: 36094426
DOI: 10.1094/PDIS-11-21-2562-RE -
Scientific Reports Jun 2022Mucormycosis is a fungal infection caused by Mucorales, with a high mortality rate. However, only a few virulence factors have been described in these organisms. This...
Mucormycosis is a fungal infection caused by Mucorales, with a high mortality rate. However, only a few virulence factors have been described in these organisms. This study showed that deletion of rfs, which encodes the enzyme for the biosynthesis of rhizoferrin, a siderophore, in Mucor lusitanicus, led to a lower virulence in diabetic mice and nematodes. Upregulation of rfs correlated with the increased toxicity of the cell-free supernatants of the culture broth (SS) obtained under growing conditions that favor oxidative metabolism, such as low glucose levels or the presence of HO in the culture, suggesting that oxidative metabolism enhances virulence through rhizoferrin production. Meanwhile, growing M. lusitanicus in the presence of potassium cyanide, N-acetylcysteine, a higher concentration of glucose, or exogenous cAMP, or the deletion of the gene encoding the regulatory subunit of PKA (pkaR1), correlated with a decrease in the toxicity of SS, downregulation of rfs, and reduction in rhizoferrin production. These observations indicate the involvement of the cAMP-PKA pathway in the regulation of rhizoferrin production and virulence in M. lusitanicus. Moreover, rfs upregulation was observed upon macrophage interaction or during infection with spores in mice, suggesting a pivotal role of rfs in M. lusitanicus infection.
Topics: Animals; Diabetes Mellitus, Experimental; Ferric Compounds; Glucose; Hydrogen Peroxide; Mice; Mucor; Siderophores; Virulence
PubMed: 35739200
DOI: 10.1038/s41598-022-14515-0 -
Life (Basel, Switzerland) May 2022Periodontitis is an inflammatory lesion in the periodontal tissue. The behavior of human periodontal ligament stem cells (hPDLSCs), which play an important role in...
High-Intensity Red Light-Emitting Diode Irradiation Suppresses the Inflammatory Response of Human Periodontal Ligament Stem Cells by Promoting Intracellular ATP Synthesis.
Periodontitis is an inflammatory lesion in the periodontal tissue. The behavior of human periodontal ligament stem cells (hPDLSCs), which play an important role in periodontal tissue regeneration, is restricted by the influence of inflammatory mediators. Photobiomodulation therapy exerts anti-inflammatory effects. The purpose of this study was to investigate the effects of light-emitting diode (LED) irradiation on the inflammatory responses of hPDLSCs. The light source was a red LED (peak wavelength: 650 nm), and the total absolute irradiance was 400 mW/cm. The inflammatory response in hPDLSCs is induced by tumor necrosis factor (TNF)-α. Adenosine triphosphate (ATP) levels and pro-inflammatory cytokine (interleukin [IL]-6 and IL-8) production were measured 24 h after LED irradiation, and the effects of potassium cyanide (KCN) were investigated. LED irradiation at 6 J/cm significantly increased the ATP levels and reduced TNF-α-induced IL-6 and IL-8 production. Furthermore, the inhibitory effect of LED irradiation on the production of pro-inflammatory cytokines was inhibited by KCN treatment. The results of this study showed that high-intensity red LED irradiation suppressed the TNF-α-stimulated pro-inflammatory cytokine production in hPDLSCs by promoting ATP synthesis. These results suggest that high-intensity red LED is a useful tool for periodontal tissue regeneration in chronically inflamed tissues.
PubMed: 35629403
DOI: 10.3390/life12050736 -
Journal of Pharmaceutical and... Jul 2019Belizatinib (BZB; TSR-011) is a next-generation anaplastic lymphoma kinase inhibitor that also inhibits tropomyosin-related kinases A/B/C. In this in-vitro study, we...
Belizatinib (BZB; TSR-011) is a next-generation anaplastic lymphoma kinase inhibitor that also inhibits tropomyosin-related kinases A/B/C. In this in-vitro study, we examined the formation of reactive metabolites from BZB using rat liver microsomes or human liver microsomes in the presence of a trapping agent (potassium cyanide) to generate iminium reactive intermediates. Identification of the in vitro BZB metabolites indicated that the major in-vitro metabolic reaction involved hydroxylation of the piperidine moiety. We identified eight in-vitro phase I metabolites and three iminium reactive intermediates, suggesting two possible BZB-bioactivation pathways. We propose that the tertiary nitrogen in the piperidine ring activates the attached benzyl carbon in addition to the two α carbons inside the ring. To our knowledge, this is the first report on the structural identification of reactive metabolites derived from BZB.
Topics: Anaplastic Lymphoma Kinase; Animals; Antineoplastic Agents; Benzamides; Chromatography, High Pressure Liquid; Humans; In Vitro Techniques; Microsomes, Liver; Molecular Structure; Potassium Cyanide; Protein Kinase Inhibitors; Rats
PubMed: 30999224
DOI: 10.1016/j.jpba.2019.04.006