-
Vasomotion in human arteries and their regulations based on ion channel regulations: 10 years study.Journal of Cellular Physiology Sep 2023Vasomotion is the oscillation of vascular tone which gives rise to flow motion of blood into an organ. As is well known, spontaneous contractile organs such as heart,...
Vasomotion is the oscillation of vascular tone which gives rise to flow motion of blood into an organ. As is well known, spontaneous contractile organs such as heart, GI, and genitourinary tract produce rhythmic contraction. It imposes or removes pressure on their vessels alternatively for exchange of many substances. It was first described over 150 years ago, however the physiological mechanism and pathophysiological implications are not well understood. This study aimed to elucidate underlying mechanisms and physiological function of vasomotion in human arteries. Conventional contractile force measurement, immunohistochemistry, and Western blot analysis were employed to study human left gastric artery (HLGA) and uterine arteries (HUA). RESULTS: Circular muscle of HLGA and/or HUA produced sustained tonic contraction by high K (50 mM) which was blocked by 2 µM nifedipine. Stepwise stretch and high K produced nerve-independent spontaneous contraction (vasomotion) (around 45% of tested tissues). Vasomotion was also produced by application of BayK 8644, 5-HT, prostagrandins, oxytocin. It was blocked by nifedipine (2 µM) and blockers of intracellular Ca stores. Inhibitors of Ca -activated Cl channels (DIDS and/or niflumic acid) and ATP-sensitive K (K ) channels inhibited vasomotion reversibly. Metabolic inhibition by sodium cyanide (NaCN) and several neuropeptides also regulated vasomotion in K channel-sensitive and -insensitive manner. Finally, we identified TMEM16A Ca -activated Cl channels and subunits of K channels (Kir 6.1/6.2 and sulfonylurea receptor 2B [SUR2B]), and c-Kit positivity by Western blot analysis. We conclude that vasomotion is sensitive to TMEM16A Ca -activated Cl channels and metabolic changes in human gastric and uterine arteries. Vasomotion might play an important role in the regulation of microcirculation dynamics even in pacemaker-related autonomic contractile organs in humans.
Topics: Humans; Ion Channels; Nifedipine; Uterine Artery; Arteries; Isometric Contraction
PubMed: 37672477
DOI: 10.1002/jcp.31067 -
Current Microbiology Sep 2023Plant growth-promoting rhizobacteria (PGPR) are beneficial microorganisms to develop microbial fertilizers. Biofertilizers can accelerate plant growth and enhance crop...
Plant growth-promoting rhizobacteria (PGPR) are beneficial microorganisms to develop microbial fertilizers. Biofertilizers can accelerate plant growth and enhance crop yields. The current research aimed to isolate and identify rhizobacterium with plant growth-promoting activity in the rhizospheric region of pistachio trees in arid and salty region of Iran. In the present study, 26 bacterial isolates were isolated from the rhizospheric region of the pistachio trees. Plant growth-promoting characteristics of isolated bacteria, including the ability to solubilize phosphate and zinc, produce hydrolyzing enzymes, and hydrogen cyanide (HCN), as well as synthesize indole-3-acetic acid (IAA) were evaluated through in vitro assays. Based on these activities, five multifunctional bacterial strains designated P1, P10, P11, P17, and P19 were then applied and their effect was studied on the growth and physiological properties of Pistacia vera L. seedlings by pot experiments under normal conditions. Finally, the most efficient strain has been identified by analysis of the 16S rRNA gene sequence. According to the results, all the isolated bacteria exhibited considerable plant growth-promoting properties. They could produce amylase (n = 26, 2 ± 0.00-13 ± 0.42 mm), lipase (n = 24, 2 ± 0.00-9 ± 0.23 mm), protease (n = 20, 1 ± 0.00-17 ± 0.0 mm), indole-3-acetic acid (n = 26, ranging from 5.05 ± 0.08 to 11.5 ± 0.11 μg/mL) and HCN (n = 24). Six isolates showed significant growth at 20% w/v NaCl. Inoculation of P1, P17, and P19 increased chlorophyll, carotenoid, and phenolic content in treated Pistacia vera L. seedlings. P1 and P11 inoculated plants showed an enhanced level of anthocyanin and proline. These most effective strains were catalase and Gram-positive bacterium and showed antibiotic sensitivity. They can consider as halotolerant PGPR, due to the growth in the presence of NaCl (20% w/v). Finally, P1 inoculated plants exhibited higher levels of sugar content. This strain showed the most similarity (99.92%-1322 bp) to Paenarthrobacter nitroguajacolicus based on 16S rRNA gene sequence. Based on the results, Paenarthrobacter nitroguajacolicus P1 with multiple PGPR can be applied as a promising candidate in the soil-Pistacia vera L. system to improve their productivity and health by increasing available nutrient content, improving photosynthetic parameters, and producing phytohormones and HCN.
Topics: Pistacia; Phosphates; Zinc; RNA, Ribosomal, 16S; Sodium Chloride; Alphaproteobacteria
PubMed: 37667111
DOI: 10.1007/s00284-023-03448-0 -
Forensic Sciences Research Jun 2023
PubMed: 37621451
DOI: 10.1093/fsr/owad015 -
Journal of Orthopaedic Surgery and... Aug 2023Elevated levels of oxidative stress as a consequence of estrogen deficiency serve as a key driver of the onset of osteoporosis (OP). In addition to increasing the risk...
BACKGROUND
Elevated levels of oxidative stress as a consequence of estrogen deficiency serve as a key driver of the onset of osteoporosis (OP). In addition to increasing the risk of bone fractures, OP can reduce the bone volume proximal to titanium nails implanted to treat these osteoporotic fractures, thereby contributing to titanium nail loosening. Sodium butyrate (NaB) is a short-chain fatty acid produced by members of the gut microbiota that exhibits robust antioxidant and anti-inflammatory properties.
METHODS
OP fracture model rats parameters including bone mineral density (BMD), new bone formation, and the number of bonelets around the implanted nail were analyzed via micro-CT scans, H&E staining, and Masson's staining. The protective effects of NaB on such osseointegration and the underlying mechanisms were further studied in vitro using MC3T3-E1 cells treated with carbonyl cyanide m-chlorophenylhydrazone (CCCP) to induce oxidative stress. Techniques including Western immunoblotting, electron microscopy, flow cytometry, alkaline phosphatase (ALP) staining, and osteoblast mineralization assays were employed to probe behaviors such as reactive oxygen species production, mineralization activity, ALP activity, protein expression, and the ability of cells to attach to and survive on titanium plates.
RESULTS
NaB treatment was found to enhance ALP activity, mineralization capacity, and Coll-I, BMP2, and OCN expression levels in CCCP-treated MC3T3-E1 cells, while also suppressing PKC and NF-κB expression and enhancing Nrf2 and HO-1 expression in these cells. NaB further suppressed intracellular ROS production and malondialdehyde levels within the cytosol while enhancing superoxide dismutase activity and lowering the apoptotic death rate. In line with these results, in vivo work revealed an increase in BMD in NaB-treated rats that was associated with enhanced bone formation surrounding titanium nails.
CONCLUSION
These findings indicate that NaB may represent a valuable compound that can be postoperatively administered to aid in treating OP fractures through the enhancement of titanium nail osseointegration.
Topics: Rats; Animals; Reactive Oxygen Species; Osseointegration; NF-kappa B; Titanium; Butyric Acid; Protein Kinase C-alpha; Carbonyl Cyanide m-Chlorophenyl Hydrazone; Nails; Osteogenesis
PubMed: 37528483
DOI: 10.1186/s13018-023-04013-y -
Materials (Basel, Switzerland) Jul 2023The production and loss of fine particles of activated carbon (AC) loaded with gold in the adsorption processes is a worldwide problem, mainly due to the behavior of...
The production and loss of fine particles of activated carbon (AC) loaded with gold in the adsorption processes is a worldwide problem, mainly due to the behavior of increasing its adsorption capacity with respect to the decrease in particle size, which becomes relevant to determine the thermodynamic and kinetic activity of the gold adsorption and the economic impact of its loss, with the escape towards the later stages of the system of adsorption, desorption, and reactivation (ADR) plants of AC. Through the adsorption of gold in a synthetic medium with sodium cyanide concentration, using different particle sizes, AC weights, and adsorption times, data were generated for analysis by three different isotherm models, resulting in a better tendency for the Freundlich isotherm, from which thermodynamic parameters of Δ equal to -2.022 kcal/mol, Δ equal to -16.710 kcal/mol, and Δ equal to -0.049 kcal/molK were obtained, which shows that it is a spontaneous, exothermic process with a lower degree of disorder. The kinetic analysis was performed with two different models, from which the pseudo-second-order model was used due to a better tendency and displayed a behavior that leaves open the interpretation of the increase in adsorption with respect to the decrease in the AC particle size but demonstrated the importance of recovering these particles in relation to their gold concentration and the economic impact from their poor recovery, which, for this case study, amounted to ~0.3 million dollars per year.
PubMed: 37512236
DOI: 10.3390/ma16144961 -
Journal of the American Chemical Society Aug 2023Protein α-N-terminal dimethylation (Nme) is an underexplored posttranslational modification (PTM) despite the increasing implications of α-N-terminal dimethylation in...
Protein α-N-terminal dimethylation (Nme) is an underexplored posttranslational modification (PTM) despite the increasing implications of α-N-terminal dimethylation in vital physiological and pathological processes across diverse species; thus, it is imperative to identify the sites of α-N-terminal dimethylation in the proteome. So far, only ∼300 α-N-terminal methylation sites have been discovered including mono-, di-, and tri-methylation, due to the lack of a pan-selective method for detecting α-N-terminal dimethylation. Herein, we introduce the three-component coupling reaction, oxidative nitrile thiazolidination (OxNiTha) for chemoselective modification of α-Nme to thiazolidine ring in the presence of selectfluor, sodium cyanide, and 1,2 aminothiols. One of the major challenges in developing a pan-specific method for the selective modification of α-Nme PTM is the competing reaction with dimethyl lysine (Kme) PTM of a similar structure. We tackle this challenge by trapping nitrile-modified Nme with aminothiols, leading to the conversion of Nme to a five-membered thiazolidine ring. Surprisingly, the 1,2 aminothiol reaction with nitrile-modified Kme led to de-nitrilation along with the de-methylation to generate monomethyl lysine (Kme). We demonstrated the application of OxNiTha reaction in pan-selective and robust modification of α-Nme in peptides and proteins to thiazolidine functionalized with varying fluorescent and affinity tags under physiological conditions. Further study with cell lysate enabled the enrichment of Nme PTM containing proteins.
Topics: Lysine; Nitriles; Thiazolidines; Protein Processing, Post-Translational; Proteome; Oxidative Stress
PubMed: 37486086
DOI: 10.1021/jacs.3c02369 -
Journal of Education & Teaching in... Jul 2022The goal of this simulation is to educate emergency medicine students, residents, attending physicians, and mid-level practitioners to recognize, diagnose, and manage...
AUDIENCE
The goal of this simulation is to educate emergency medicine students, residents, attending physicians, and mid-level practitioners to recognize, diagnose, and manage acute cyanide toxicity.
INTRODUCTION
Cyanide has an almond scent and is a naturally occurring compound. It is present within many different types of plants and fruits including apricots, apples, peaches, lima beans, and cassava plants but is harmless.1 The trace amounts of cyanide found within organic materials is of little concern because its high reactivity causes it to be metabolized rapidly and create other compounds. However, modern synthetic materials such as plastics, papers, textiles, and machinery can release a much greater concentration of hydrogen cyanide when exposed to high temperatures.1 As the use of contemporary nitrogen-containing synthetic polymers has expanded, the possibility of cyanide toxicity has become increasingly common and severe. Hydrogen cyanide is especially dangerous to humans because the gaseous form reacts quickly upon inhalation.2When cyanide enters the body via inhalation, it blocks the cells from utilizing oxygen by binding to the cytochrome oxidase in the mitochondria.2 The inability of the cell to use oxygen forces cells from aerobic metabolism into anaerobic metabolism. Anaerobic metabolism results in the production of lactic acid, which causes metabolic acidosis.3 The human body cannot sustain itself with the lack of oxygen and anaerobic metabolism for a prolonged period of time. Ultimately, the body will suffer cardiorespiratory arrest.1Symptoms of cyanide toxicity include headache, nausea, shortness of breath, and altered mental status.1 These are similar to those of carbon monoxide and carbon dioxide inhalation. However, symptoms of cyanide toxicity cannot be treated with supplemental oxygen as carbon monoxide and carbon dioxide are. Cyanide toxicity must be treated with an antidote - sodium thiosulfate, sodium nitrite, and hydroxocobalamin.4 Each of the antidotes works by binding with the highly reactive cyanide, neutralizing the compound, and converting it into a water-soluble product that will be cleared through renal excretion.4Fire victims often present to the emergency department critically ill. They will likely have obvious external thermal burns and traumatic injuries; however, it is important for emergency personnel to recognize the respiratory distress and metabolic derangements that are most likely occurring due to toxic gas inhalation. People who are trapped within a burning structure are exposed to carbon monoxide, carbon dioxide, and cyanide from the combustion of contents within the building. These toxic gasses will cause severe tissue hypoxia without significant vital sign changes.5 The respiratory distress and metabolic compromise will be acutely more fatal than the obvious external injuries and burns. The challenge in treating these patients is for the healthcare team to know the differential diagnoses, prioritize airway, breathing and circulation, and to empirically treat the patient as if they have a confirmed exposure.It is estimated that 35% of all fire victims have toxic levels of cyanide upon arrival to the emergency room.2 Acute cyanide toxicity can become fatal within minutes; however, a prompt diagnosis and treatment can be lifesaving. Unfortunately, due to the limited amount of time the human body can sustain anaerobic metabolism and tissue hypoxia, blood test results are not available in time to be clinically applicable.2 Rather, the emergency room personnel must begin treatment immediately upon recognizing that toxic smoke inhalation may have occurred.We understand the importance of knowing how to treat fire victims. Therefore, the goal of this simulation case is to expose the emergency providers to cyanide poisoning and educate emergency providers about the critical steps of how to approach, diagnose, and treat cyanide toxicity.
EDUCATIONAL OBJECTIVES
After the completion of this simulation, participants will have learned how to: 1) identify clues of smoke inhalation based on a physical examination; 2) identify smoke inhalation-induced airway compromise and perform definitive management; 3) create a differential diagnosis for victims of fire cyanide poisoning, carbon monoxide, and carbon dioxide; 4) appropriately treat cyanide poisoning; 5) demonstrate the importance of preemptively treating for cyanide poisoning; 6) perform an initial physical examination and identify physical marks suggesting the patient is a fire and smoke inhalation victim; and 7) familiarize themselves with the Cyanokit and treatment with hydroxocobalamin.
EDUCATIONAL METHODS
This is a high-fidelity simulation case in which participants work through a case of a patient who has been exposed to fire. The participants will be able to work hands-on to evaluate, diagnose, and treat cyanide poisoning in an emergency event. Afterwards, there will be a small group discussion and debriefing of the case in order to review patient care skills, interpersonal and communication skills, medical knowledge, and system-based practice.
RESEARCH METHODS
The participants were instructed to complete a survey before and after the simulation case. A quality Likert Scale was used to assess the participants' comfort level of diagnosing, treating, and managing a patient with toxic smoke inhalation. A score of 1 represented a negative experience and 5 represented a very positive experience. The surveys were then reviewed by the research team to determine if the simulation case improved the participants' comfort level. The survey answers were compared collectively, as well as individually, and were analyzed between the pre-simulation and post-simulation results.
RESULTS
Our simulation involved 25 participants: 20 participants were emergency medicine resident physicians and 5 were 4th-year medical students. In the pre-simulation survey, participants reported a mean of 2.7 out of 5 when asked to rate their confidence in their ability to treat a smoke inhalation victim. The post-simulation survey showed a significant increase to a mean of 3.5 out of 5. Participants were also asked to evaluate the usefulness of the simulation: 15 participants rated the case as a 5, which represented "very useful," and the other 10 participants rated the case as a 4, which represented "useful." The mean value when asked to assess the simulation case's usefulness and applicability in emergency medicine was 4.6 out of 5.
DISCUSSION
This simulation allows providers to focus on victims of fire. Fire victims are often critically ill and require time sensitive treatment. This simulation gives providers a chance to review their knowledge and prepare them for real life cases. Based on the survey results, the simulation improved awareness and understanding of the symptoms of acute cyanide toxicity and improved the participant's ability to recognize, diagnose, and treat cyanide poisoning.
TOPICS
Cyanide toxicity, carbon monoxide toxicity, cyanide antidote, fire victim, intubation, airway intervention, oxygen treatment, history taking, lab testing ordering, symptom identification, interpretation of lab results, emergency medicine simulation.
PubMed: 37465777
DOI: 10.21980/J80W76 -
Frontiers in Bioinformatics 2023Autofluorescence imaging of the coenzymes reduced nicotinamide (phosphate) dinucleotide (NAD(P)H) and oxidized flavin adenine dinucleotide (FAD) provides a label-free...
Autofluorescence imaging of the coenzymes reduced nicotinamide (phosphate) dinucleotide (NAD(P)H) and oxidized flavin adenine dinucleotide (FAD) provides a label-free method to detect cellular metabolism and phenotypes. Time-domain fluorescence lifetime data can be analyzed by exponential decay fitting to extract fluorescence lifetimes or by a fit-free phasor transformation to compute phasor coordinates. Here, fluorescence lifetime data analysis by biexponential decay curve fitting is compared with phasor coordinate analysis as input data to machine learning models to predict cell phenotypes. Glycolysis and oxidative phosphorylation of MCF7 breast cancer cells were chemically inhibited with 2-deoxy-d-glucose and sodium cyanide, respectively; and fluorescence lifetime images of NAD(P)H and FAD were obtained using a multiphoton microscope. Machine learning algorithms built from either the extracted lifetime values or phasor coordinates predict MCF7 metabolism with a high accuracy (∼88%). Similarly, fluorescence lifetime images of M0, M1, and M2 macrophages were acquired and analyzed by decay fitting and phasor analysis. Machine learning models trained with features from curve fitting discriminate different macrophage phenotypes with improved performance over models trained using only phasor coordinates. Altogether, the results demonstrate that both curve fitting and phasor analysis of autofluorescence lifetime images can be used in machine learning models for classification of cell phenotype from the lifetime data.
PubMed: 37455808
DOI: 10.3389/fbinf.2023.1210157 -
Food Chemistry Dec 2023This study investigated different methods to produce N-carboxymethyl-lysine (CML)-enriched bovine serum albumin (BSA) as alternatives to the classical approach using...
This study investigated different methods to produce N-carboxymethyl-lysine (CML)-enriched bovine serum albumin (BSA) as alternatives to the classical approach using glyoxylic acid (GA) and sodium cyanoborohydride (NaBHCN) which results in toxic hydrogen cyanide (HCN). The reaction of GA (6 mmol/L) and NaBHCN (21 mmol/L) to produce CML remained the most effective with CML yields of 24-35%, followed by 13-24% using 300 mmol/L glyoxal (GO). GA promoted specific modification of lysine to CML, and fewer structural modifications of the BSA molecule compared with GO, as evidenced by fluorescence and proteomic analyses. GO promoted greater arginine modification compared with GA (76 vs 23%). Despite structural changes to BSA with GO, murine fecal clearance of CML was similar to literature values. Hence, BSA glycation with 300 mmol/L glyoxal is a suitable alternative to GA and NaBHCN for generating CML-enriched protein free of HCN, but a CML-only fortification model remains to be described.
Topics: Animals; Mice; Serum Albumin, Bovine; Glycation End Products, Advanced; Proteomics; Serum Albumin; Glyoxal
PubMed: 37450953
DOI: 10.1016/j.foodchem.2023.136815 -
Molecules (Basel, Switzerland) Jun 2023This paper describes the three-step synthesis of TBS-MAC, a masked acyl cyanide (MAC) and a versatile one-carbon oxidation state three synthon. We have developed a...
This paper describes the three-step synthesis of TBS-MAC, a masked acyl cyanide (MAC) and a versatile one-carbon oxidation state three synthon. We have developed a scalable and detailed synthesis that involves: (1) acetylation of malononitrile to form the sodium enolate, (2) protonation of the enolate to form acetylmalononitrile, and (3) epoxidation of the enol, rearrangement to an unstable alcohol, and TBS-protection to form the title compound. Both the sodium enolate and acetylmalononitrile are bench-stable precursors to the intermediate hydroxymalononitrile, which can be converted to other MAC reagents beyond TBS by varying the protecting group (Ac, MOM, EE, etc.).
Topics: Cyanides; Carboxylic Acids; Alcohols; Sodium
PubMed: 37446749
DOI: 10.3390/molecules28135087