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1.
J Phys Chem Lett ; 15(16): 4430-4436, 2024 Apr 25.
Article En | MEDLINE | ID: mdl-38626390

Elucidating isotope exchange between atmospheric trace molecular species is important for environment monitoring, climate control studies, and a fundamental understanding of atmospheric chemistry. Here, we provide direct experimental evidence of oxygen-isotopic exchange between carbon dioxide (CO2) and nitrogen dioxide (NO2), which are simultaneously emitted into the atmosphere from common sources. A combined near-infrared and UV-vis optical cavity-enhanced experimental investigation along with quantum-chemical calculations followed by a reaction modeling study revealed that CO2 and NO2 can communicate isotopically by near-ultraviolet-driven NO2 photolysis. Our results found evidence for a near-barrierless (1.67 kcal/mol) nitrate-containing complex having a very short lifetime (∼13 ns) which facilitates the transfer of 18O-isotopes from 18O12C16O to N16O16O, leading to isotopic depletion of 18O in 18O12C16O, thus opening a new gas-phase isotope-selective chemical transformation mechanism in the lower atmosphere. This isotope exchange study may serve as a new window into the fundamental understanding of isotopic photochemistry, oxygen isotopic fractionations, and climate modeling.

2.
Exp Eye Res ; 242: 109852, 2024 May.
Article En | MEDLINE | ID: mdl-38460719

Oxidative stress plays a pivotal role in the pathogenesis of several neurodegenerative diseases. Retinal degeneration causes irreversible death of photoreceptor cells, ultimately leading to vision loss. Under oxidative stress, the synthesis of bioactive sphingolipid ceramide increases, triggering apoptosis in photoreceptor cells and leading to their death. This study investigates the effect of L-Cycloserine, a small molecule inhibitor of ceramide biosynthesis, on sphingolipid metabolism and the protection of photoreceptor-derived 661W cells from oxidative stress. The results demonstrate that treatment with L-Cycloserine, an inhibitor of Serine palmitoyl transferase (SPT), markedly decreases bioactive ceramide and associated sphingolipids in 661W cells. A nontoxic dose of L-Cycloserine can provide substantial protection of 661W cells against H2O2-induced oxidative stress by reversing the increase in ceramide level observed under oxidative stress conditions. Analysis of various antioxidant, apoptotic and sphingolipid pathway genes and proteins also confirms the ability of L-Cycloserine to modulate these pathways. Our findings elucidate the generation of sphingolipid mediators of cell death in retinal cells under oxidative stress and the potential of L-Cycloserine as a therapeutic candidate for targeting ceramide-induced degenerative diseases by inhibiting SPT. The promising therapeutic prospect identified in our findings lays the groundwork for further validation in in-vivo and preclinical models of retinal degeneration.


Apoptosis , Ceramides , Cycloserine , Oxidative Stress , Sphingolipids , Oxidative Stress/drug effects , Cycloserine/pharmacology , Animals , Ceramides/metabolism , Ceramides/pharmacology , Mice , Sphingolipids/metabolism , Apoptosis/drug effects , Photoreceptor Cells, Vertebrate/drug effects , Photoreceptor Cells, Vertebrate/metabolism , Photoreceptor Cells, Vertebrate/pathology , Serine C-Palmitoyltransferase/metabolism , Serine C-Palmitoyltransferase/antagonists & inhibitors , Hydrogen Peroxide/toxicity , Hydrogen Peroxide/pharmacology , Cell Line , Retinal Degeneration/metabolism , Retinal Degeneration/prevention & control , Retinal Degeneration/pathology , Retinal Degeneration/drug therapy , Blotting, Western , Enzyme Inhibitors/pharmacology , Cell Survival/drug effects
3.
Foodborne Pathog Dis ; 21(4): 220-227, 2024 Apr.
Article En | MEDLINE | ID: mdl-38190304

Foodborne gastroenteritis outbreaks owing to Salmonella enterica serovar Weltevreden (Salmonella Weltevreden) represent a significant global public health problem. In the past two decades, Salmonella Weltevreden has emerged as a dominant foodborne pathogen, especially in South-East Asian countries. This report describes a community foodborne outbreak of gastroenteritis caused by Salmonella Weltevreden in August 2022 following consumption of panipuri from a street vendor in the Polba block in Hooghly district, West Bengal, India. This food item was consumed by 185 people, of whom 129 had acute watery diarrhea with other clinical symptoms and 65 of them were admitted to different District hospitals for treatment. Stool specimens collected from hospitalized cases were positive for S. enterica, and further serotyped as Salmonella Weltevreden. All the Salmonella Weltevreden strains possessed the Salmonella pathogenicity islands associated genes (invA/E, orgA, ttrc, ssaQ, mgtC, misL, spi4D), the enterotoxin (stn), and hyperinvasive locus gene (hilA). Except erythromycin, all the strains were susceptible for commonly used antimicrobials in the treatment of diarrhea. The XbaI-based pulsed-field gel electrophoresis analysis indicated that all the isolates responsible for the recent outbreak were similar, but diverged from other Salmonella Weltevreden that were previously reported in West Bengal. This report indicates that foodborne infection is a major public health concern in India and demands to strengthen capacity-building measures at the local health care levels for linking causative agents of outbreaks.


Gastroenteritis , Salmonella enterica , Humans , Serogroup , Salmonella enterica/genetics , Salmonella , Gastroenteritis/epidemiology , Diarrhea/epidemiology , Disease Outbreaks , India/epidemiology , Electrophoresis, Gel, Pulsed-Field
4.
Chemistry ; 30(12): e202303890, 2024 Feb 26.
Article En | MEDLINE | ID: mdl-38147010

We have established a supporting-electrolyte free electrochemical method for the synthesis of indazolylindazolones through oxygen reduction reaction (eORR) induced 1,3-oxo-amination of 2H-indazoles where 2H-indazole is used as both aminating agent as well as the precursor of indazolone. Moreover, we have merged indazolone and indazole to get unsymmetrical indazolylindazolones through direct electrochemical cross-dehydrogenative coupling (CDC). This exogenous metal-, oxidant- and catalyst-free protocol delivered a number of multi-functionalized products with high tolerance of diverse functional groups.

5.
Biomolecules ; 13(12)2023 11 23.
Article En | MEDLINE | ID: mdl-38136563

The bioactive sphingolipid sphingosine-1-phosphate (S1P) acts as a ligand for a family of G protein-coupled S1P receptors (S1PR1-5) to participate in a variety of signaling pathways. However, their specific roles in the neural retina remain unclear. We previously showed that S1P receptor subtype 2 (S1PR2) is expressed in murine retinas, primarily in photoreceptors and bipolar cells, and its expression is altered by retinal stress. This study aims to elucidate the role of S1PR2 in the mouse retina. We examined light responses by electroretinography (ERG), structural differences by optical coherence tomography (OCT), and protein levels by immunohistochemistry (IHC) in wild-type (WT) and S1PR2 knockout (KO) mice at various ages between 3 and 6 months. We found that a- and b-wave responses significantly increased at flash intensities between 400~2000 and 4~2000 cd.s/m2, respectively, in S1PR2 KO mice relative to those of WT controls at baseline. S1PR2 KO mice also exhibited significantly increased retinal nerve fiber layer (RNFL) and outer plexiform layer (OPL) thickness by OCT relative to the WT. Finally, in S1PR2 KO mice, we observed differential labeling of synaptic markers by immunohistochemistry (IHC) and quantitative reverse transcription polymerase chain reaction (RT-qPCR). These results suggest a specific involvement of S1PR2 in the structure and synaptic organization of the retina and a potential role in light-mediated functioning of the retina.


Electroretinography , Retina , Mice , Animals , Sphingosine-1-Phosphate Receptors/metabolism , Retina/metabolism , Signal Transduction , Mice, Knockout
6.
bioRxiv ; 2023 Sep 05.
Article En | MEDLINE | ID: mdl-37732206

The bioactive sphingolipid sphingosine-1-phosphate (S1P) acts as a ligand for a family of G protein-coupled S1P receptors (S1PR1-5) to participate in a variety of signaling pathways. However, their specific roles in the neural retina remain unclear. We previously showed that S1P receptor subtype 2 (S1PR2) is expressed in murine retinas, primarily in photoreceptors and bipolar cells, and its expression is altered by retinal stress. This study aims to elucidate the role of S1PR2 in the mouse retina. We examined light responses by electroretinography (ERG), structural differences by optical coherence tomography (OCT), and protein levels by immunohistochemistry (IHC) in wild-type (WT) and S1PR2 knockout (KO) mice at various ages between 3 and 6 months. We found that a- and b-wave responses significantly increased at flash intensities between 400∼2000 and 4∼2,000 cd.s/m 2 respectively, in S1PR2 KO mice relative to those of WT controls at baseline. S1PR2 KO mice also exhibited significantly increased retinal nerve fiber layer (RNFL) and outer plexiform layer (OPL) thickness by OCT relative to the WT. Finally, in S1PR2 KO mice, we observed differential labeling of synaptic markers by immunohistochemistry (IHC) and quantitative reverse transcription polymerase chain reaction (RT-qPCR). These results suggest a specific involvement of S1PR2 in the structure and synaptic organization of the retina and a potential role in light-mediated functioning of the retina.

7.
Opt Lett ; 48(15): 4141-4144, 2023 Aug 01.
Article En | MEDLINE | ID: mdl-37527138

Plasmonic random lasers have drawn significant attention recently due to their versatility, low threshold, and the possibility of achieving tunable and coherent/incoherent outputs. However, in this Letter, the phenomenon of replica symmetry breaking is reported in intensity fluctuations of a rarely used colloidal plasmonic random laser (RL) illumination. Triangular nanosilver scatter particles produced incoherent RL action when used in a dimethylformamide (DMF) environment in a Rhodamine-6G gain medium. The use of gold-coated triangular nanosilver as the scatterer in place of triangular nanosilver offered a dual contribution of scattering and lower photo-reabsorption, which caused a reduction in the lasing threshold energy of 39% compared to that obtained with the latter. Further, due to its long-term photostability and chemical properties, a phase transition from the photonic paramagnetic to the glassy phase is observed experimentally in the RL system used. Interestingly, the transition occurs at approximately the lasing threshold value, which is a consequence of stronger correlation of modal behaviors at high input pump energies.

8.
Environ Sci Pollut Res Int ; 30(9): 22590-22605, 2023 Feb.
Article En | MEDLINE | ID: mdl-36303003

Kinetics of the reaction of IO radicals with methanol (MeOH) and ethanol (EtOH) were experimentally studied in the gas phase using pulsed laser photolysis-cavity ring-down spectroscopy (PLP-CRDS). IO radicals were produced in situ at the reaction zone by photolysing a mixture of precursors (CH3I + O3 + N2) at 248 nm and thereby electronically excited at 445.04 nm. The rate coefficients for the reactions of (IO + MeOH) and (IO + EtOH) were measured at a total pressure of 60 Torr/N2 in the range of 258-360 K. At room temperature, the experimental rate coefficients of the title reactions were measured to be [Formula: see text] and [Formula: see text]. Dependencies of the kinetics with photolysis laser fluence and experimental pressures were verified. Effects of pressure over the kinetic behaviour of the studied systems were observed to be insignificant within the statistical uncertainties when studied in the range of ~ 30-150 Torr/N2, whereas a minor and linear fluence dependency was observed within the studied limit. From the measured kinetic parameters, the atmospheric lifetimes of MeOH and EtOH were calculated in the tropospherically relevant conditions regarding their reactions with important atmospheric oxidants like Cl atom, OH and IO radicals. To complement experimental results, kinetics and thermochemistry for the title reactions were investigated theoretically via canonical variational transition state (CVT) theory in combination with small curvature tunnelling (SCT) corrections with a dual-level Interpolated Single Point Energy (ISPE) approach at the CCSD(T)/def2-QZVPP//M06-2X/def2-TZVPP level of theory/basis set in the temperatures between 200 and 400 K. Good degree of agreement was encountered between experimentally measured and theoretically calculated rate coefficients. This article also discusses the thermochemical parameters and kinetic branching ratios (BRs) of all the pathways involved in the title reactions.


Alcohols , Physics , Kinetics , Temperature , Spectrum Analysis
9.
Cells ; 11(19)2022 09 30.
Article En | MEDLINE | ID: mdl-36231042

Sphingolipids (SPLs) play a diverse role in maintaining cellular homeostasis. Dysregulated SPL metabolism is associated with pathological changes in stressed and diseased cells. This study investigates differences in SPL metabolism between cultured human primary retinal endothelial (HREC) and murine microglial cells (BV2) in normal conditions (normal glucose, NG, 5 mM) and under high-glucose (HG, 25 mM)-induced stress by sphingolipidomics, immunohistochemistry, biochemical, and molecular assays. Measurable differences were observed in SPL profiles between HREC and BV2 cells. High-glucose treatment caused a >2.5-fold increase in the levels of Lactosyl-ceramide (LacCer) in HREC, but in BV2 cells, it induced Hexosyl-Ceramides (HexCer) by threefold and a significant increase in Sphingosine-1-phosphate (S1P) compared to NG. Altered SPL profiles coincided with changes in transcript levels of inflammatory and vascular permeability mediators in HREC and inflammatory mediators in BV2 cells. Differences in SPL profiles and differential responses to HG stress between endothelial and microglial cells suggest that SPL metabolism and signaling differ in mammalian cell types and, therefore, their pathological association with those cell types.


Microglia , Sphingolipids , Animals , Ceramides/metabolism , Glucose , Humans , Inflammation Mediators , Mammals/metabolism , Mice , Microglia/metabolism , Sphingolipids/metabolism
10.
Org Biomol Chem ; 20(37): 7361-7376, 2022 09 28.
Article En | MEDLINE | ID: mdl-36107011

Recently, direct C-H bond activation and functionalization has become a prodigious and hot topic among synthetic organic chemists due to its step-economic nature and substantial synthetic versatility. On the other hand, quinoxaline, a fused bicycle of benzene and pyrazine, has omnipresent applications in medicinal-, industrial- and materials chemistry. The presence of the N-1 atom in 2-arylquinoxaline enables chelation formation with a metal catalyst leading to the formation of ortho-substituted products. In this review, all articles related to the ortho C-H bond functionalization of 2-arylquinoxalines published up to May 2022 are highlighted.


Benzene , Transition Elements , Catalysis , Pyrazines , Quinoxalines , Transition Elements/chemistry
11.
J Phys Chem A ; 126(36): 6135-6147, 2022 Sep 15.
Article En | MEDLINE | ID: mdl-36054843

Formyl (HCO) radicals were generated in situ in the gas phase via the photolysis of glyoxal in N2 at 248 nm using the pulsed laser photolysis-cavity ring-down spectrometry technique, and the absorption cross-section of the radical was measured to be σHCO = (5.3 ± 0.9) × 10-19 cm2 molecule-1 at 298 K and 615.75 nm, which was the probing wavelength. The kinetics of the reactions of HCO radicals with ethyl formate (EF) and ethyl acetate (EA) were investigated experimentally in the temperature range of 260-360 (±2) K at a pressure of 60 Torr/N2. The absolute rate coefficient for the reaction between HCO and EF was measured to be kHCO+EFExpt(298 K) = (1.39 ± 0.30) × 10-14 cm3 molecule-1 s-1 at ambient temperature, whereas that for the reaction of HCO with EA was measured tobe kHCO+EATheory(298 K) = (2.05 ± 0.43) × 10-14 cm3 molecule-1 s-1. The reaction of HCO with EA was faster than that with EF, which might be due to the greater stability of the formed radical intermediate due to hyperconjugative and inductive effects. The dependency of the measured kinetics on experimental pressures and laser fluences was examined within a certain range. To complement the experiments, kinetics of the title reactions in the temperature range of 200-400 K were deciphered theoretically via the canonical variational transition-state theory with small-curvature tunneling and interpolated single-point energy (CVT/SCT/ISPE) method using a dual-level approach at the CCSD(T)/cc-pVTZ//MP2/6-311++G(d,p) level of theory/basis set. A good degree of agreement was detected between the rate coefficients measured experimentally and those calculated theoretically both at room temperature and throughout the range of temperatures studied. The kinetic branching ratios and thermochemistry of the reactions were investigated to understand the thermodynamic feasibility and kinetic lability of each pathway throughout the studied temperatures. Atmospheric implications of these reactions of HCO radicals are also discussed.

13.
Ocul Surf ; 25: 101-107, 2022 07.
Article En | MEDLINE | ID: mdl-35714913

PURPOSE: Sphingolipids (SPL) are a class of lipid molecules that play important functional and structural roles in our body and are a component of meibum. Sphingomyelinases (SMases) are key enzymes in sphingolipid metabolism that hydrolyze sphingomyelin (SM) and generate ceramide (Cer). The purpose of this study was to examine relationships between ocular surface SMases, SPL composition, and parameters of Meibomian gland dysfunction (MGD). METHODS: Individuals were grouped by meibum quality (n = 25 with poor-quality, MGD, and n = 25 with good-quality, control). Meibum and tears were analyzed with LC-MS to quantify SPL classes: Cer, Hexosyl-Ceramide (Hex-Cer), SM, Sphingosine (Sph), and sphingosine 1-phosphate (S1P). SMase activity in tears were quantified using a commercially available 'SMase assay'. Statistical analysis included multiple linear regression analyses to assess the impact of SMase activity on lipid composition, as well as ocular surface symptoms and signs of MGD. RESULTS: Demographic characteristics were similar between the two groups. nSMase and aSMase levels were lower in the poor vs good quality group. aSMase activity in tears negatively correlated with SM in meibum and tears and positively with Sph in meibum and S1P in tears. Lower SMase activity were associated with signs of MGD, most notably Meibomian gland dropout. CONCLUSION: This study suggests that individuals with MGD have reduced enzymatic activity of SMases in tears. Specifically, individuals with poor vs good meibum quality were noted to have alterations in SMase activity and SPL composition of meibum and tears which may reflect deviations from normal lipid metabolism in individuals with MGD.


Eyelid Diseases , Meibomian Gland Dysfunction , Ceramides/metabolism , Eyelid Diseases/diagnosis , Humans , Meibomian Glands/metabolism , Sphingolipids/metabolism , Sphingomyelin Phosphodiesterase/analysis , Sphingomyelin Phosphodiesterase/metabolism , Tears/metabolism
14.
Mol Neurobiol ; 59(6): 3873-3887, 2022 Jun.
Article En | MEDLINE | ID: mdl-35426574

Hydroxychloroquine (HCQ) is an anti-malarial drug but also widely used to treat autoimmune diseases like arthritis and lupus. Although there have been multiple reports of the adverse effect of prolonged HCQ usage on the outer retina, leading to bull's-eye maculopathy, the effect of HCQ toxicity on the inner retina as well as on overall visual functions has not been explored in detail. Furthermore, lack of an established animal model of HCQ toxicity hinders our understanding of the underlying molecular mechanisms. Here, using a small clinical study, we confirmed the effect of HCQ toxicity on the inner retina, in particular the reduction in central inner retinal thickness, and established a mouse model of chronic HCQ toxicity that recapitulates the effects observed in human retina. Using the mouse model, we demonstrated that chronic HCQ toxicity results in loss of inner retinal neurons and retinal ganglion cells (RGC) and compromises visual functions. We further established that HCQ treatment prevents autophagosome-lysosome fusion and alters the sphingolipid homeostasis in mouse retina. Our results affirm the notion that HCQ treatment causes early damage to the inner retina and affects visual functions before leading to characteristic toxicity in the macular region of the outer retina, 'bull's-eye maculopathy.' We also provide insights into the underlying molecular mechanisms of HCQ retinal toxicity that may involve autophagy-lysosomal defects and alterations in sphingolipid metabolism.


Antirheumatic Agents , Macular Degeneration , Retinal Diseases , Animals , Antirheumatic Agents/adverse effects , Autophagosomes , Hydroxychloroquine/adverse effects , Lysosomes , Mice , Retina , Retinal Diseases/chemically induced , Retinal Diseases/drug therapy , Sphingolipids , Tomography, Optical Coherence/methods
15.
J Phys Chem Lett ; 13(13): 3079-3088, 2022 Apr 07.
Article En | MEDLINE | ID: mdl-35353525

Aggregation-induced enhancement (AIE) in the photoluminescence quantum yield (PLQY) from 12.5 to 51% in the N,N-dimethylformamide (DMF)-stabilized Au nanocluster (AuNC) system is reported here. The self-assembling of AuNC has been achieved via hydrogen bonding interaction, which is further utilized in designing the AuNC_DCM system for realizing a Förster resonance energy transfer (FRET)-based white LED (WLED), having CIE coordinates of (0.35, 0.29). The solution-processed fabrication strategy used, has given us the liberty to optimize its components for optimal full-spectrum light output. The CIE coordinates of the designed WLED have been improved further to (0.33, 0.32), with a high color rendering index of 93 and correlated color temperature of 5620 K by incorporating a green emitter, namely nitrogen-doped graphene quantum dots (NGQD), in the AuNC_DCM system. The excellent spectral quality of the as-designed WLED and the repeatability of the proposed fabrication method will make the developed AuNCs_DCM FRET conjugate useful in practical photonic applications.

16.
Phys Chem Chem Phys ; 23(45): 25974-25993, 2021 Nov 24.
Article En | MEDLINE | ID: mdl-34783802

The gas-phase kinetics of the reactions of IO radicals with ethyl formate (EF) and ethyl acetate (EA) were investigated experimentally using cavity ring-down spectroscopy (CRDS). IO radicals were generated in situ in the CRD reaction zone by photolyzing a mixture of (CH3I + O3 + N2) at 248 nm and thereby probed at 445.04 nm. The rate coefficients for the reactions (IO + EF) and (IO + EA) were measured at a total pressure of 65 Torr of N2 in the temperature range of 258-358 and 260-360 K, respectively. The rate coefficients for the reactions (IO + EF) and (IO + EA) were measured experimentally at room temperature to be kExpt,298KIO+EF = (3.38 ± 0.67) × 10-14 and kExpt,298KIO+EA = (1.56 ± 0.30) × 10-13 cm3 molecule-1 s-1, respectively. The effects of pressure and photolysis laser fluence on the kinetics of test reactions were found to be negligible within the experimental uncertainties for the studied range. To complement our experimental findings, the kinetics of the title reactions were investigated theoretically using canonical variational transition state theory (CVT) with small curvature tunnelling (SCT) at the CCSD(T)//M06-2X/def2-SV(P) level of theory in temperatures between 200 and 400 K. Very good agreement was observed between the experimentally measured and theoretically calculated rate coefficients for both the reactions at 298 K. The thermochemical parameters as well as the branching ratios for the title reactions are also discussed in this study.

17.
Opt Lett ; 46(19): 4879-4882, 2021 Oct 01.
Article En | MEDLINE | ID: mdl-34598223

Here, we report hitherto unobserved local field (LF)-assisted pump wavelength-dependent nonlinear optical (NLO) effects of three-photon (3PA)-induced four-photon absorption (4PA) at 532 nm and two-photon-induced 3PA at 730 nm in triangular-shaped core-shell Ag-Au nanoparticles (TrAg@Au) by femtosecond Z-scan. The shell thickness-dependent enhancement in the LF is observed by a COMSOL simulation. The intensity-dependent interplay between saturable and reverse-saturable absorptions along with switching of nonlinear (NL) phase is reported at 730 nm, showing the superiority of TrAg@Au in optical switching (OS). The optical limiting (OL) threshold (Fth) of 5.9(6.5)mJ/cm2 at 730 (532) nm boost their potential over benchmarked materials.

18.
J Phys Chem A ; 125(40): 8869-8881, 2021 Oct 14.
Article En | MEDLINE | ID: mdl-34587445

The reactivity of 2-ethoxy ethanol with OH radicals was experimentally measured in the temperature range of 278-363 K using the pulsed laser photolysis-laser-induced fluorescence (PLP-LIF) technique. The rate coefficient at room temperature was measured to be (1.14 ± 0.03) × 10-11 cm3 molecule-1 s-1, and the Arrhenius expression was derived to be kexpt278-363K = (1.61 ± 0.35) × 10-13 exp{(1256 ± 236)/T} cm3 molecule-1 s-1. Computational calculations were performed to compute the kinetics of the titled reaction in the temperature range of 200-400 K using advanced methods incorporated with tunneling correction at the CCSD(T)/aug-cc-pVTZ//M06-2X/6-31+G(d,p) level of theory. The Arrhenius expression derived from the computationally calculated rate coefficients is ktheo200-400K = (1.59 ± 0.35) × 10-13exp{(1389 ± 62)/T} cm3 molecule-1 s-1. The feasibility of each reaction pathway was also determined using the calculated thermochemical parameters. Atmospheric implication parameters such as cumulative atmospheric lifetime and photochemical ozone creation potential were calculated and are discussed in this paper.

19.
Mol Neurobiol ; 58(11): 5564-5580, 2021 Nov.
Article En | MEDLINE | ID: mdl-34365584

Traumatic brain injury (TBI) causes neuroinflammation and neurodegeneration leading to various pathological complications such as motor and sensory (visual) deficits, cognitive impairment, and depression. N-3 polyunsaturated fatty acid (n-3 PUFA) containing lipids are known to be anti-inflammatory, whereas the sphingolipid, ceramide (Cer), is an inducer of neuroinflammation and degeneration. Using Fat1+-transgenic mice that contain elevated levels of systemic n-3 PUFA, we tested whether they are resistant to mild TBI-mediated sensory-motor and emotional deficits by subjecting Fat1-transgenic mice and their WT littermates to focal cranial air blast (50 psi) or sham blast (0 psi, control). We observed that visual function in WT mice was reduced significantly following TBI but not in Fat1+-blast animals. We also found Fat1+-blast mice were resistant to the decline in motor functions, depression, and fear-producing effects of blast, as well as the reduction in the area of oculomotor nucleus and increase in activated microglia in the optic tract in brain sections seen following blast in WT mice. Lipid and gene expression analyses confirmed an elevated level of the n-3 PUFA eicosapentaenoic acid (EPA) in the plasma and brain, blocking of TBI-mediated increase of Cer in the brain, and decrease in TBI-mediated induction of Cer biosynthetic and inflammatory gene expression in the brain of the Fat1+ mice. Our results demonstrate that suppression of ceramide biosynthesis and inflammatory factors in Fat1+-transgenic mice is associated with significant protection against the visual, motor, and emotional deficits caused by mild TBI. This study suggests that n-3 PUFA (especially, EPA) has a promising therapeutic role in preventing neurodegeneration after TBI.


Affective Symptoms/prevention & control , Brain Concussion/blood , Cadherins/physiology , Fatty Acids, Omega-3/blood , Head Injuries, Closed/blood , Movement Disorders/prevention & control , Vision Disorders/prevention & control , Affective Symptoms/blood , Affective Symptoms/etiology , Animals , Brain Chemistry , Brain Concussion/complications , Brain Concussion/psychology , Cadherins/genetics , Ceramides/biosynthesis , Depression/blood , Depression/etiology , Depression/prevention & control , Disease Resistance , Fatty Acids, Omega-3/physiology , Fear , Female , Head Injuries, Closed/complications , Head Injuries, Closed/psychology , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Movement Disorders/blood , Movement Disorders/etiology , Neuroinflammatory Diseases , Open Field Test , Oxidative Stress , Recombinant Proteins/metabolism , Sphingolipids/analysis , Sphingomyelin Phosphodiesterase/analysis , Vision Disorders/blood , Vision Disorders/etiology
20.
Photochem Photobiol Sci ; 20(7): 859-873, 2021 Jul.
Article En | MEDLINE | ID: mdl-34196955

The gas-phase kinetics of phenyl radical (·C6H5) with ethyl formate (HCO2Et, EF) was investigated experimentally using ultrasensitive laser-based cavity ring-down spectroscopy (CRDS). Phenyl radicals were generated by photolyzing nitrosobenzene (C6H5NO) at 248 nm and thereby probed at 504.8 nm. The rate coefficients for the (phenyl radical + EF) reaction were investigated between the temperatures of 260 and 361 K and at a pressure of 61 Torr with nitrogen (N2) as diluent. The temperature-dependent Arrhenius expression for the test reaction was obtained as: [Formula: see text]=(1.20  ±  0.16) × 10-13 exp[-(435.6  ±  50.0)/T] cm3 molecule-1 s-1 and the rate coefficient at room temperature was measured out to be: [Formula: see text]=(4.54  ±  0.42) × 10-14 cm3 molecule-1 s-1. The effects of pressure and laser fluence on the kinetics of the test reaction were found to be negligible within the experimental uncertainties. To complement the experimental findings, kinetics for the reaction of phenyl radicals with EF was investigated theoretically using Canonical Variational Transition State Theory (CVT) with Small Curvature Tunnelling (SCT) at CCSD(T)/cc-pVDZ//B3LYP/6-31 + G(d,p) level of theory in the temperatures between 200 and 400 K. The theoretically calculated rate coefficients for the title reaction were expressed in the Arrhenius form as: [Formula: see text]= (1.48  ±  0.56) × 10-38 × T8.47 × exp[(2431.3  ±  322.0)/T] cm3 molecule-1 s-1 and the corresponding rate coefficient at room temperature was calculated to be: [Formula: see text]= 4.91 × 10-14 cm3 molecule-1 s-1. A very good agreement was observed between the experimentally measured and theoretically calculated rate coefficients at 298 K. Thermochemical parameters as well as branching ratios for the reaction of (phenyl radical + EF) are also discussed in this manuscript.

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