Objective:To investigate the effects of coenzyme Q10(CoQ10)supplementation on post-vitrification embryo development and gross morphology.Methods:Balb/c mouse embryos were cultured in potassium simplex optimised medium...Objective:To investigate the effects of coenzyme Q10(CoQ10)supplementation on post-vitrification embryo development and gross morphology.Methods:Balb/c mouse embryos were cultured in potassium simplex optimised medium(KSOM)with varying CoQ10 concentrations[0(control),20,40,and 60μM].The most effective CoQ10 concentration(40μM)was selected for subsequent post-vitrification morphology study.Embryos were randomly divided into four groups:Group A(non-vitrified without CoQ10),Group B(non-vitrified with CoQ10),Group C(vitrified without CoQ10),and Group D(vitrified with CoQ10),followed by vitrification at the 8-cell stage.Survival rates and development until the blastocyst stage were evaluated through morphological examinations using ASEBIR's system,distinguishing normal and abnormal embryos.Results:Supplementation of 40μM CoQ10 significantly increased blastocyst formation(95%)compared to the control group(92%),20μM(62%),and 60μM(56%)(P<0.001).Following vitrification,Group D exhibited a significant increase in blastocyst formation(92%)compared to Group C(82%)(P<0.05).Morphological assessments indicated superior embryo quality in Group B over Group D during the cleavage stage,morula,and blastocyst(P<0.05).Conclusions:CoQ10 supplementation exhibits promising potential to enhance preimplantation embryo development,increase blastocyst formation rates,and improve embryo quality post-vitrification.This offers a promising approach to mitigate oxidative stress on embryos,potentially improving overall assisted reproductive technology outcomes.展开更多
Background Fertility declines in high-parity sows.This study investigated whether parity-dependent declines in embryonic survival and reproductive performance could be restored by dietary coenzyme Q10(CoQ10)supplement...Background Fertility declines in high-parity sows.This study investigated whether parity-dependent declines in embryonic survival and reproductive performance could be restored by dietary coenzyme Q10(CoQ10)supplementation.Methods Two experiments were performed.In Exp.1,30 young sows that had completed their 2nd parity and 30 high-parity sows that had completed their 10^(th)parity,were fed either a control diet(CON)or a CON diet supple-mented with 1 g/kg CoQ10(+CoQ10)from mating until slaughter at day 28 of gestation.In Exp.2,a total of 314 post-weaning sows with two to nine parities were fed the CON or+CoQ10 diets from mating throughout gestation.Results In Exp.1,both young and high-parity sows had a similar number of corpora lutea,but high-parity sows had lower plasma CoQ10 concentrations,down-regulated genes involved with de novo CoQ10 synthesis in the endome-trium tissues,and greater levels of oxidative stress markers in plasma and endometrium tissues.High-parity sows had fewer total embryos and alive embryos,lower embryonic survival,and greater embryo mortality than young sows.Dietary CoQ10 supplementation increased the number of live embryos and the embryonic survival rate to levels simi-lar to those of young sows,as well as lowering the levels of oxidative stress markers.In Exp.2,sows showed a parity-dependent decline in plasma CoQ10 levels,and sows with more than four parities showed a progressive decline in the number of total births,live births,and piglets born effective.Dietary supplementation with CoQ10 increased the number of total births,live births,and born effective,and decreased the intra-litter covariation coefficients and the percentage of sows requiring farrowing assistance during parturition.Conclusions Dietary CoQ10 supplementation can improve the embryonic survival and reproductive performance of gestating sows with high parity,probably by improving the development of uterine function.展开更多
Coenzyme Q10 is widely used in food,cosmetics and pharmaceuticals,possessing a broad market.Rhodobacter sphaeroides is enriched in natural coenzyme Q10 and is becoming an important microorganism for producing natural ...Coenzyme Q10 is widely used in food,cosmetics and pharmaceuticals,possessing a broad market.Rhodobacter sphaeroides is enriched in natural coenzyme Q10 and is becoming an important microorganism for producing natural coenzyme Q10.The paper reviewed the biosynthesis pathways of coenzyme Q10 in R.sphaeroides and the advances in enhancement of coenzyme Q10 production in R.sphaeroides based on metabolic engineering.展开更多
Photocatalytic oxidation of primary and secondary benzyl alcohol to corresponding benzaldehyde or acetophenone using Acr+Cl04- or PhAcr+Cl04- as photocatalysts under visible light irradiation at room temperature.
Glaucoma, the leading cause of visual impairment and irreversible blindness worldwide, is a multifactorial, progressive optic neuropathy characterized by loss of retinal ganglion cells, alterations of the optic nerve ...Glaucoma, the leading cause of visual impairment and irreversible blindness worldwide, is a multifactorial, progressive optic neuropathy characterized by loss of retinal ganglion cells, alterations of the optic nerve head, and specific visual field defects. Clinical evidence shows that intraocular pressure is the major risk factor of the treatable disease. However, in some patients, glaucoma develops and continues to progress despite normal intraocular pressure values, suggesting that other risk factors are involved in the disease. Consequently, neuroprotective treatments, focused on preventing retinal ganglion cells death by acting on different therapeutic strategies but not focused on intraocular pressure reduction, has therefore become of great interest. In this contest, coenzyme Q10, showing evidence in slowing or reversing pathological changes typical of the disease, has been proposed as a potential neuroprotective agent in glaucoma. In this review, we describe the possible mechanisms of action of coenzyme Q10 and the recent evidence in literature regarding the neuroprotective activity of the molecule.展开更多
In order to explore the effect and mechanisms of tumor necrosis factor-α (TNF-α) on the activity of the acyl coenzyme A: cholesteryl acyltransferase (ACAT), THP-I monocytes were cul- tured and induced to differ...In order to explore the effect and mechanisms of tumor necrosis factor-α (TNF-α) on the activity of the acyl coenzyme A: cholesteryl acyltransferase (ACAT), THP-I monocytes were cul- tured and induced to differentiate into macrophages with phorbol ester. TNF-α (60 ng/mL) was added at different time points into the macrophage-containing medium and the ACAT enzyme activity was measured by quantifying the incorporation of [1-^14C] oleoyl CoA into cholesteryl esters. The expression of ACAT-1 protein and mRNA was respectively detected by Western blotting and RT-PCR in THP-1 macrophages 24 h after treatment with TNF-α (60 ng/mL). The results indicated that ACAT activity in THP-I macrophages treated with TNF-α was increased in a time-dependent manner. The expression levels of ACAT-1 protein and mRNA were significantly increased in THP-I macrophages after treatment with TNF-α (P〈0.05). It was suggested that TNF-α could increase the activity of ACAT in THP-1 macrophages by up-regulating the expression of ACAT-1 gene.展开更多
In order to increase the production efficiency of coenzyme Q10, the original strain Agrobacterium tumefaciens ATCC 4452 was mutated by means of Nitrogen ions implantation. A mutant strain, ATX 12, with high contents o...In order to increase the production efficiency of coenzyme Q10, the original strain Agrobacterium tumefaciens ATCC 4452 was mutated by means of Nitrogen ions implantation. A mutant strain, ATX 12, with high contents of coenzyme Q10 was selected. Subsequently, the conditions such as carbohydrate concentration, nitrogen source concentration, inoculum's size, seed age, aeration and temperature which might affect the production of CoQ10 were investigated in detail. Under optimal conditions, the maximum concentration of the intracellular CoQ10 reached 200.3 mg/L after 80 h fed-batch fermentation, about 245% increasing in CoQ10 production after ion implantation, compared to the original strain.展开更多
For the sake of improving patient compliance and sustainability of chemotherapy healthcare system, both TC and CoQ10 were formulated as solid lipid nanoparticles (SLNs). The study was focused on establishing and valid...For the sake of improving patient compliance and sustainability of chemotherapy healthcare system, both TC and CoQ10 were formulated as solid lipid nanoparticles (SLNs). The study was focused on establishing and validating a simple and reproducible spectrophotometric method for simultaneous determination of TC and CoQ10 in their binary mixture or pharmaceutical dosage forms. A new method based on simultaneous estimation of drug mixture without prior separation was developed. Validation parameters were checked with International Conference on Harmonization (ICH) guidelines. The accuracy and reproducibility of proposed method was statistically compared to HPLC. The TC and CoQ10 were quantified at absorptivity wavelengths of 236 nm and 275 nm, respectively. Calibration curves obeyed Beer’s law in range of 2–14 μg/ml with a correlation coefficient (R^2) of 0.999 in both methanol and simplified simulated intestinal fluid (SSIF). The %means recovery of TC and Co Q10 in pure state or binary mixture at various concentration levels were all around 100%.The low values of SD and %RSD (<2%) confirm high precision and accuracy of the proposed method. Formulated SLNs showed different %means recovery in range 81–92% for TC and 32–59% for CoQ10. The data obtained by applying simultaneous Vierordt’s equations showed no statistical significance in comparison to HPLC. Vierordt’s method was successfully applied as a simple, accurate, precise, and economical analysis method for estimating TC and CoQ10 concentrations in pure state, binary mixture and pharmaceutical dosage forms.展开更多
Inherited photoreceptor degeneration(IPD):The human retina is a highly specialised tissue that enables the perception of light across a range of intensities and colours.It covers about65%of the inner surface of the...Inherited photoreceptor degeneration(IPD):The human retina is a highly specialised tissue that enables the perception of light across a range of intensities and colours.It covers about65%of the inner surface of the eye and contains three layers of cells:the outer nuclear layer(ONL)containing the cell bodies and nuclei of the light-sensitive rod and cone photoreceptorswhose photopigment-containing outer segments form the photoreceptor layer; the inner nuclear layer (INL) containing bipolar, horizontal and amacrine cells; and the ganglion cell layer (GCL) from which the optic nerve arises. There are two layers of synaptic connections between these three layers: the photoreceptors synapse with second order neurons, mainly bi- polar cells, in the outer plexiform layer (OPL), while in turn the bipolar cells form connections in the inner plexiform layer (IPL) with ganglion cells. The retinal pigment epithelium (RPE) lies directly behind the photoreceptor layer, is heavily pigmented to reduce scattering of light, and is essential for the nourishment, maintenance and metabolism of photoreceptors.展开更多
In order to investigate the enzymatic properties of the 4CL1 of Populus tomentosa, the recombinant expression vector pQE31-4CL 1 was constructed. The recombinant was identified by three restriction endonucleases, then...In order to investigate the enzymatic properties of the 4CL1 of Populus tomentosa, the recombinant expression vector pQE31-4CL 1 was constructed. The recombinant was identified by three restriction endonucleases, then the vector pQE31-4CL 1 was transformed into expression host M15 (pREP4) and induced by isopropyl-a-D-thiogalactoside (IPTG) to express 60 kD fused protein Pt4CL1. The biologically active Pt4CL1, expressed as soluble protein, was achieved with 0.6 mmol'L-1 IPTG induction as the expression temperature declined from 37 to 28℃. The 6-His tag facilitates affinity binding to Ni^2+-nitrolotriacetic acid (NTA) and enables one-step purification to acquire the molecular SDS-PAGE electrophoresis purity of the active 4CL1 protein by agarose coupled with Ni^2+-NTA affinity chromatography. The optimal substrate for Pt4CL 1 was 4-coumarate.展开更多
Coenzyme Q10(Co Q10) is an essential cofactor in the mitochondrial respiratory pathway and also functions as a lipid-soluble antioxidant. Co Q10 deficiency has been implicated in many clinical disorders and aging. Pri...Coenzyme Q10(Co Q10) is an essential cofactor in the mitochondrial respiratory pathway and also functions as a lipid-soluble antioxidant. Co Q10 deficiency has been implicated in many clinical disorders and aging. Primary Co Q10 deficiency is a group of recessively inherited diseases caused by mutations in any gene involved in the Co Q10 biosynthesis pathway. Although primary Co Q10 deficiency is rare, its diagnosis is important because it is potentially treatable with exogenous Co Q10. Multiple system atrophy(MSA) was recently shown to be linked to mutations in the COQ2 gene, one of the genes involved in the Co Q10 biosynthesis pathway. MSA is relatively common in adult-onset neurodegenerative diseases characterized by Parkinsonism, cerebellar ataxia and autonomic failures. Because COQ2 mutations are associated with an increased risk of MSA, oral Co Q10 supplementation may be beneficial for MSA, as for other primary Co Q10 deficiencies. Statins are 3-hydroxy-3-methylglutaryl coenzyme A inhibitors that inhibit the biosynthesis of cholesterol, as well as the synthesis of mevalonate, a critical intermediate in cholesterol synthesis. Statin therapy has been associ-ated with a variety of muscle complaints from myalgia to rhabdomyolysis. Statin treatment carries a potential risk of Co Q10 deficiency, although no definite evidence has implicated CQ10 deficiency as the cause of statinrelated myopathy.展开更多
<p style="margin-left:10.0pt;"> <br /> </p> <p style="margin-left:10.0pt;"> <span>The coenzyme B<sub>12</sub> dependent glutamate mutase is composed of two...<p style="margin-left:10.0pt;"> <br /> </p> <p style="margin-left:10.0pt;"> <span>The coenzyme B<sub>12</sub> dependent glutamate mutase is composed of two apoenzyme proteins subunits;S and E<sub>2</sub>, which while either fused or separate assemble with coenzyme B<sub>12</sub> to form an active holoenzyme (E<sub>2</sub>S<sub>2</sub>-B<sub>12</sub>) for catalyzing the reversible isomerization between (<i>S</i>)-glutamate and (2<i>S</i>, 3<i>S</i>)-3-methylas</span><span>- </span><span>partate. In order to assay the activity of glutamate mutase by UV spectrophotometry, this reaction is often coupled with methylaspartase which deaminates (2<i>S</i>, 3<i>S</i>)-3-methylaspartate to form mesaconate (<i>λ</i><sub>max</sub> = 240 nm, </span><span>Ɛ</span><sub><span>240</span></sub><span> = 3.8 mM<sup>-1</sup>·cm<sup>-1</sup>). The activities of different reconstitutions of glutamate mu<span>tase from separate apoenzyme components S and E in varied amount</span></span><span>s</span><span> of </span><span>coenzyme B<sub>12</sub> and adenosylpeptide B<sub>12</sub> as cofactors were measured by this assay and used to reveal the binding properties of the cofactor by the Michaelis</span><span>- </span><span>Menten Method. The values of <i>K<sub>m</sub></i> for coenzyme B<sub>12</sub> in due to reconstitutions of holoenzyme in 2, 7 and 14 S: E were determined as;1.12 ± 0.04 μM, 0.7 ± 0.05 μM and 0.52 ± 0.06 μM, respectively, so as those of adenosylpeptide B<sub>12</sub>;1.07 ± 0.04 μM and 0.35 ± 0.05 μM as obtained from respective 2 and 14 S: E compositions of holoenzyme. Analysis of these kinetics results curiously as<span>sociate</span></span><span>s</span><span> the increasing affinity of cofactors to apoenzyme with</span><span> </span><span>increased amount of component S used in reconstituting holoenzyme from separate</span><span> apoenzyme components and cofactor.</span><span> Moreover, in these studies a new method for assaying the activity of glutamate mutase was developed, whereby glutamate mutase activity is measured via depletion of NADH (<i>λ</i><sub>max</sub> = 340 nm, </span><span>Ɛ</span><sub><span>340</span></sub><span> = 6.3 mM<sup>-1</sup>·cm<sup>-1</sup>) as determined by UV spectrophotometry after addition of (2<i>S</i>,<span> 3<i>S</i>)-3-methylaspartate and pyruvate to a mixture of E<sub>2</sub>S<sub>2</sub>-B<sub>12</sub> and two auxiliary </span><span>holoenzymes system;pyridoxal-5-phosphate dependent glutamate-pyruvate </span><span>aminotransferase and N</span>ADH dependent (<i>R</i>)-2-hydroxyglutarate dehydrogenas<span>e. The activity of glutamate-pyruvate aminotransferase was relatively complete recovered upon the addition of (<i>S</i>)-glutamate and pyruvate to the mixtures of hologlutamate-pyruvate aminotransferase and (<i>R</i>)-2-hydroxylglutarate</span> dehydrogenase which were incubated with each putative inhibitor of glutamate mutase. Additionally, the new assay was used to determine the kinetic constants of (2<i>S</i>, 3<i>S</i>)-3-methylaspartate in the reaction of glutamate mutase as <i>K</i><sub>m</sub>= 7 ± 0.07 mM and <i>k</i><sub>cat</sub>= 0.54 ± 0.6 s<sup>-1</sup>. Application of Briggs-Haldane formula allowed the calculation of an equilibrium constant of the reversible isomerization, <i>K</i><sub>eq</sub> = [(<i>S</i>)-glutamate] × [(2<i>S</i>, 3<i>S</i>)-3-methylaspartate]<sup>-1</sup> = 16, where the kinetic constants of (<i>S</i>)-glutamate were determined by the standard methylaspartase coupled assay.<span></span></span> </p> <p> <br /> </p>展开更多
Objective: To study the effect of levocarnitine + coenzyme Q10 adjuvant therapy on vasoactive molecules, endothelial injury and oxidative stress in patients with chronic heart failure. Methods: A total of 90 patients ...Objective: To study the effect of levocarnitine + coenzyme Q10 adjuvant therapy on vasoactive molecules, endothelial injury and oxidative stress in patients with chronic heart failure. Methods: A total of 90 patients with chronic heart failure who were treated in the hospital between December 2014 and December 2016 were collected and divided into control group and observation group by random number table method, 45 cases in each group. Control group received conventional therapy, and observation group received levocarnitine + coenzyme Q10 adjuvant therapy on the basis of conventional therapy. The differences in vasoactive molecule, endothelial injury and oxidative stress levels were compared between the two groups before and after treatment. Results: Before treatment, the differences in vasoactive molecule, endothelial injury and oxidative stress levels were not statistically significant between the two groups of patients. After treatment, serum vasoactive molecules ET-1, AngⅡ and TXB2 contents of observation group were lower than those of control group while NO content was higher than that of control group;endothelial function indexes FMD level was higher than that of control group;serum oxidative stress indexes SOD and T-AOC contents were higher than those of control group while MDA and ROS contents were lower than those of control group. Conclusion: Levocarnitine + coenzyme Q10 adjuvant therapy can optimize the vascular activity, and reduce the endothelial injury and systemic oxidative stress response in patients with chronic heart failure.展开更多
BACKGROUND Immune-mediated necrotizing myopathy is a rare autoimmune myopathy characterized by muscle weakness and elevated serum creatine kinase,with unique skeletal muscle pathology and magnetic resonance imaging fe...BACKGROUND Immune-mediated necrotizing myopathy is a rare autoimmune myopathy characterized by muscle weakness and elevated serum creatine kinase,with unique skeletal muscle pathology and magnetic resonance imaging features.CASE SUMMARY In this paper,two patients are reported:One was positive for anti-signal recognition particle antibody,and the other was positive for anti-3-hydroxy-3-methylglutaryl coenzyme A reductase antibody.CONCLUSION The clinical characteristics and treatment of the two patients were analysed,and the literature was reviewed to improve the recognition,diagnosis,and treatment of this disease.展开更多
Termite queens and kings live longer than nonreproductive workers.Several molecular mechanisms contributing to their long lifespan have been investigated;however,the underlying biochemical explanation remains unclear....Termite queens and kings live longer than nonreproductive workers.Several molecular mechanisms contributing to their long lifespan have been investigated;however,the underlying biochemical explanation remains unclear.Coenzyme Q(CoQ),a component of the mitochondrial electron transport chain,plays an essential role in the lipophilic antioxidant defense system.Its beneficial effects on health and longevity have been well studied in several organisms.Herein,we demonstrated that long-lived termite queens have significantly higher levels of the lipophilic antioxidant CoQ_(10) than workers.Liquid chromatography analysis revealed that the levels of the reduced form of CoQ_(10) were 4 fold higher in the queen's body than in the worker's body.In addition,queens showed 7 fold higher levels of vitamin E,which plays a role in antilipid peroxidation along with CoQ,than workers.Furthermore,the oral administration of CoQ_(10) to termites increased the CoQ_(10) redox state in the body and their survival rate under oxidative stress.These findings suggest that CoQ_(10) acts as an efficient lipophilic antioxidant along with vitamin E in long-lived termite queens.This study provides essential biochemical and evolutionary insights into the relationship between CoQ_(10) concentrations and termite lifespan extension.展开更多
Cholesterol plays several structural and metabolic roles that are vital for human biology. It spreads along the entire plasma membrane of the cell, modulating fluidity and concentrating in specialized sphingolipid-ric...Cholesterol plays several structural and metabolic roles that are vital for human biology. It spreads along the entire plasma membrane of the cell, modulating fluidity and concentrating in specialized sphingolipid-rich domains called rafts and caveolae. Cholesterol is also a substrate for steroid hormones. However, too much cholesterol can lead to pathological pictures such as atherosclerosis, which is a consequence of the accumu- lation of cholesterol into the cells of the artery wall. The liver is considered to be the metabolic power station of mammalians, where cholesterol homeostasis relies on an intricate network of cellular processes whose deregulations can lead to several life-threatening pathologies, such as familial and age-related hypercholesterolemia. Cholesterol homeostasis maintenance is carried out by: biosynthesis, via 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) activity; uptake, through low density lipoprotein receptors (LDLr); lipoprotein release in the blood; storage by esterification; and degradation and conversion into bile acids. Both HMGR and LDLr are transcribed as a function of cellular sterol amount by a family of transcription factors called sterol regulatory element binding proteins that are responsible for the maintenance of cholesterol homeostasis through an intricate mechanism of regulation. Cholesterol obtained by hepatic de novo synthesis can be esterified and incorporated into apolipoprotein B-100-containing very low density lipoproteins, which are then secreted into the bloodstream for transport to peripheral tissues. Moreover, dietary cholesterol is transferred from the intestine to the liver by high density lipoproteins (HDLs); all HDL particles are internalized in the liver, interacting with the hepatic scavenger receptor (SR-B1). Here we provide an updated overview of liver cholesterol metabolism regulation and deregulation and the causes of cholesterol metabolism-related diseases. Moreover, current pharmacological treatment and novel hypocho-lesterolemic strategies will also be introduced.展开更多
The objective of the present study was to examine the effect of different weaning methods on the ruminal methanogenic archaea composition and diversity in Holstein calves.Thirty-six newborn Holstein bull calves were a...The objective of the present study was to examine the effect of different weaning methods on the ruminal methanogenic archaea composition and diversity in Holstein calves.Thirty-six newborn Holstein bull calves were assigned to 1 of 3 treatments:(1)conventional weaning(d 56)and fed a high proportion of solid feed(CWS);(2)conventional weaning(d 56)and fed a high proportion of liquid feed(CWL);(3)early weaning(d 42)and fed with a high proportion of solid feed(EWS).High-throughput sequencing of the methyl coenzyme M reductase(mcr A)gene,which encodes theα-subunit of methyl coenzyme M reductase-the enzyme that catalyzes the final step in methanogenesis was used to determine the composition and diversity of rumen methanogens.No significant difference(P>0.05)was observed for operational taxonomic units(OTUs)or richness indices,but diversity indices increased(P<0.05)for calves fed high dietary solids.Predominant families across the three treatments were Methanobacteriaceae,Thermoplasmataceae and Methanomassiliicoccaceae.Calves in the EWS treatment had a higher(P<0.05)relative abundance of Methanobrevibacter sp.strain AbM4 and Methanosphaera stadtmanae,while calves in the CWL treatment had a higher(P<0.05)abundance of Methanosphaera sp.strain SM9.A positive(P<0.05)relationship was identified between butyrate and Methanobrevibacter sp.strain AbM4.In conclusion,the composition and diversity of methanogens in the rumen of Holstein calves varied under the different weaning methods.This study identified a positive relationship between butyrate and Methanobrevibacter sp.strain AbM4,potentially reflecting correlations between ruminal fermentation variables and methanogenesis function.These in-depth analyses provide further understanding of weaning methods for intensified production systems.展开更多
The Persian Gulf War of 1990 to 1991 involved the deployment of nearly 700,000 American troops to the Middle East.Deployment-related exposures to toxic substances such as pesticides,nerve agents,pyridostigmine bromide...The Persian Gulf War of 1990 to 1991 involved the deployment of nearly 700,000 American troops to the Middle East.Deployment-related exposures to toxic substances such as pesticides,nerve agents,pyridostigmine bromide(PB),smoke from burning oil wells,and petrochemicals may have contributed to medical illness in as many as 250,000 of those American troops.The cluster of chronic symptoms,now referred to as Gulf War Illness(GWI),has been studied by many researchers over the past two decades.Although over$500 million has been spent on GWI research,to date,no cures or condition-specific treatments have been discovered,and the exact pathophysiology remains elusive.Using the 2007 National Institute of Health(NIH)Roadmap for Medical Research model as a reference framework,we reviewed studies of interventions involving GWI patients to assess the progress of treatment-related GWI research.All GWI clinical trial studies reviewed involved investigations of existing interventions that have shown efficacy in other diseases with analogous symptoms.After reviewing the published and ongoing registered clinical trials for cognitivebehavioral therapy,exercise therapy,acupuncture,coenzyme Q10(CoQ10),mifepristone,and carnosine in GWI patients,we identified only four treatments(cognitive-behavioral therapy,exercise therapy,CoQ10,and mifepristone)that have progressed beyond a phase II trial.We conclude that progress in the scientific study of therapies for GWI has not followed the NIH Roadmap for Medical Research model.Establishment of a standard case definition,prioritized GWI research funding for the characterization of the pathophysiology of the condition,and rapid replication and adaptation of early phase,single site clinical trials could substantially advance research progress and treatment discovery for this condition.展开更多
The imbalance of reactive oxygen species and antioxidants is considered to be an important factor in the cellular injury of the inner ear. At present, great attention has been placed on oxidative stress. However,littl...The imbalance of reactive oxygen species and antioxidants is considered to be an important factor in the cellular injury of the inner ear. At present, great attention has been placed on oxidative stress. However,little is known about fighting oxidative stress. In the current study, we evaluated antioxidant-induced cochlear damage by applying several different additional antioxidants. To determine whether excessive antioxidants can cause damage to cochlear cells, we treated cochlear explants with 50 m M M40403, a superoxide dismutase mimetic, 50 m M coenzyme Q-10, a vitamin-like antioxidant, or 50 m M d-methionine, an essential amino acid and the important antioxidant glutathione for 48 h. Control cochlear explants without the antioxidant treatment maintained their normal structures after incubation in the standard serum-free medium for 48 h, indicating the maintenance of the inherent oxidative and antioxidant balance in these cochlear explants. In contrast, M40403 and coenzyme Q-10-treated cochlear explants displayed significant hair cell damage together with slight damage to the auditory nerve fibers.Moreover, d-methiodine-treated explants exhibited severe damage to the surface structure of hair cells and the complete loss of the spiral ganglion neurons and their peripheral fibers. These results indicate that excessive antioxidants are detrimental to cochlear cells, suggesting that inappropriate dosages of antioxidant treatments can interrupt the balance of the inherent oxidative and antioxidant capacity in the cell.展开更多
基金supported by the Fundamental Research Grant Scheme(FRGS)[FRGS/1/2020/SKK06/UNIKL/02/1],from the Ministry of Higher Education,Malaysia.
文摘Objective:To investigate the effects of coenzyme Q10(CoQ10)supplementation on post-vitrification embryo development and gross morphology.Methods:Balb/c mouse embryos were cultured in potassium simplex optimised medium(KSOM)with varying CoQ10 concentrations[0(control),20,40,and 60μM].The most effective CoQ10 concentration(40μM)was selected for subsequent post-vitrification morphology study.Embryos were randomly divided into four groups:Group A(non-vitrified without CoQ10),Group B(non-vitrified with CoQ10),Group C(vitrified without CoQ10),and Group D(vitrified with CoQ10),followed by vitrification at the 8-cell stage.Survival rates and development until the blastocyst stage were evaluated through morphological examinations using ASEBIR's system,distinguishing normal and abnormal embryos.Results:Supplementation of 40μM CoQ10 significantly increased blastocyst formation(95%)compared to the control group(92%),20μM(62%),and 60μM(56%)(P<0.001).Following vitrification,Group D exhibited a significant increase in blastocyst formation(92%)compared to Group C(82%)(P<0.05).Morphological assessments indicated superior embryo quality in Group B over Group D during the cleavage stage,morula,and blastocyst(P<0.05).Conclusions:CoQ10 supplementation exhibits promising potential to enhance preimplantation embryo development,increase blastocyst formation rates,and improve embryo quality post-vitrification.This offers a promising approach to mitigate oxidative stress on embryos,potentially improving overall assisted reproductive technology outcomes.
基金supported by the National Key Research and Development Program of China(2022YFD1301300).
文摘Background Fertility declines in high-parity sows.This study investigated whether parity-dependent declines in embryonic survival and reproductive performance could be restored by dietary coenzyme Q10(CoQ10)supplementation.Methods Two experiments were performed.In Exp.1,30 young sows that had completed their 2nd parity and 30 high-parity sows that had completed their 10^(th)parity,were fed either a control diet(CON)or a CON diet supple-mented with 1 g/kg CoQ10(+CoQ10)from mating until slaughter at day 28 of gestation.In Exp.2,a total of 314 post-weaning sows with two to nine parities were fed the CON or+CoQ10 diets from mating throughout gestation.Results In Exp.1,both young and high-parity sows had a similar number of corpora lutea,but high-parity sows had lower plasma CoQ10 concentrations,down-regulated genes involved with de novo CoQ10 synthesis in the endome-trium tissues,and greater levels of oxidative stress markers in plasma and endometrium tissues.High-parity sows had fewer total embryos and alive embryos,lower embryonic survival,and greater embryo mortality than young sows.Dietary CoQ10 supplementation increased the number of live embryos and the embryonic survival rate to levels simi-lar to those of young sows,as well as lowering the levels of oxidative stress markers.In Exp.2,sows showed a parity-dependent decline in plasma CoQ10 levels,and sows with more than four parities showed a progressive decline in the number of total births,live births,and piglets born effective.Dietary supplementation with CoQ10 increased the number of total births,live births,and born effective,and decreased the intra-litter covariation coefficients and the percentage of sows requiring farrowing assistance during parturition.Conclusions Dietary CoQ10 supplementation can improve the embryonic survival and reproductive performance of gestating sows with high parity,probably by improving the development of uterine function.
基金Supported by Talent Project of Sichuan University of Science&Engineering(2015RC27)Meat Processing Key Laboratory of Sichuan Province(16R-27)
文摘Coenzyme Q10 is widely used in food,cosmetics and pharmaceuticals,possessing a broad market.Rhodobacter sphaeroides is enriched in natural coenzyme Q10 and is becoming an important microorganism for producing natural coenzyme Q10.The paper reviewed the biosynthesis pathways of coenzyme Q10 in R.sphaeroides and the advances in enhancement of coenzyme Q10 production in R.sphaeroides based on metabolic engineering.
文摘Photocatalytic oxidation of primary and secondary benzyl alcohol to corresponding benzaldehyde or acetophenone using Acr+Cl04- or PhAcr+Cl04- as photocatalysts under visible light irradiation at room temperature.
文摘Glaucoma, the leading cause of visual impairment and irreversible blindness worldwide, is a multifactorial, progressive optic neuropathy characterized by loss of retinal ganglion cells, alterations of the optic nerve head, and specific visual field defects. Clinical evidence shows that intraocular pressure is the major risk factor of the treatable disease. However, in some patients, glaucoma develops and continues to progress despite normal intraocular pressure values, suggesting that other risk factors are involved in the disease. Consequently, neuroprotective treatments, focused on preventing retinal ganglion cells death by acting on different therapeutic strategies but not focused on intraocular pressure reduction, has therefore become of great interest. In this contest, coenzyme Q10, showing evidence in slowing or reversing pathological changes typical of the disease, has been proposed as a potential neuroprotective agent in glaucoma. In this review, we describe the possible mechanisms of action of coenzyme Q10 and the recent evidence in literature regarding the neuroprotective activity of the molecule.
基金This project was supported by a grant from the National Natural Sciences Foundation of China (No. 30170378)
文摘In order to explore the effect and mechanisms of tumor necrosis factor-α (TNF-α) on the activity of the acyl coenzyme A: cholesteryl acyltransferase (ACAT), THP-I monocytes were cul- tured and induced to differentiate into macrophages with phorbol ester. TNF-α (60 ng/mL) was added at different time points into the macrophage-containing medium and the ACAT enzyme activity was measured by quantifying the incorporation of [1-^14C] oleoyl CoA into cholesteryl esters. The expression of ACAT-1 protein and mRNA was respectively detected by Western blotting and RT-PCR in THP-1 macrophages 24 h after treatment with TNF-α (60 ng/mL). The results indicated that ACAT activity in THP-I macrophages treated with TNF-α was increased in a time-dependent manner. The expression levels of ACAT-1 protein and mRNA were significantly increased in THP-I macrophages after treatment with TNF-α (P〈0.05). It was suggested that TNF-α could increase the activity of ACAT in THP-1 macrophages by up-regulating the expression of ACAT-1 gene.
基金National Natural Science Foundation of China(No.20576132)
文摘In order to increase the production efficiency of coenzyme Q10, the original strain Agrobacterium tumefaciens ATCC 4452 was mutated by means of Nitrogen ions implantation. A mutant strain, ATX 12, with high contents of coenzyme Q10 was selected. Subsequently, the conditions such as carbohydrate concentration, nitrogen source concentration, inoculum's size, seed age, aeration and temperature which might affect the production of CoQ10 were investigated in detail. Under optimal conditions, the maximum concentration of the intracellular CoQ10 reached 200.3 mg/L after 80 h fed-batch fermentation, about 245% increasing in CoQ10 production after ion implantation, compared to the original strain.
文摘For the sake of improving patient compliance and sustainability of chemotherapy healthcare system, both TC and CoQ10 were formulated as solid lipid nanoparticles (SLNs). The study was focused on establishing and validating a simple and reproducible spectrophotometric method for simultaneous determination of TC and CoQ10 in their binary mixture or pharmaceutical dosage forms. A new method based on simultaneous estimation of drug mixture without prior separation was developed. Validation parameters were checked with International Conference on Harmonization (ICH) guidelines. The accuracy and reproducibility of proposed method was statistically compared to HPLC. The TC and CoQ10 were quantified at absorptivity wavelengths of 236 nm and 275 nm, respectively. Calibration curves obeyed Beer’s law in range of 2–14 μg/ml with a correlation coefficient (R^2) of 0.999 in both methanol and simplified simulated intestinal fluid (SSIF). The %means recovery of TC and Co Q10 in pure state or binary mixture at various concentration levels were all around 100%.The low values of SD and %RSD (<2%) confirm high precision and accuracy of the proposed method. Formulated SLNs showed different %means recovery in range 81–92% for TC and 32–59% for CoQ10. The data obtained by applying simultaneous Vierordt’s equations showed no statistical significance in comparison to HPLC. Vierordt’s method was successfully applied as a simple, accurate, precise, and economical analysis method for estimating TC and CoQ10 concentrations in pure state, binary mixture and pharmaceutical dosage forms.
基金Work in Dr.Shu’s lab was supported by the Rosetrees Trust(No.M160 and M160-F1)the Fight for Sight,the Glasgow Children’s Hospital Charity(No.YRSS/PSG/2014)the Visual Research Trust(No.VR2014)
文摘Inherited photoreceptor degeneration(IPD):The human retina is a highly specialised tissue that enables the perception of light across a range of intensities and colours.It covers about65%of the inner surface of the eye and contains three layers of cells:the outer nuclear layer(ONL)containing the cell bodies and nuclei of the light-sensitive rod and cone photoreceptorswhose photopigment-containing outer segments form the photoreceptor layer; the inner nuclear layer (INL) containing bipolar, horizontal and amacrine cells; and the ganglion cell layer (GCL) from which the optic nerve arises. There are two layers of synaptic connections between these three layers: the photoreceptors synapse with second order neurons, mainly bi- polar cells, in the outer plexiform layer (OPL), while in turn the bipolar cells form connections in the inner plexiform layer (IPL) with ganglion cells. The retinal pigment epithelium (RPE) lies directly behind the photoreceptor layer, is heavily pigmented to reduce scattering of light, and is essential for the nourishment, maintenance and metabolism of photoreceptors.
文摘In order to investigate the enzymatic properties of the 4CL1 of Populus tomentosa, the recombinant expression vector pQE31-4CL 1 was constructed. The recombinant was identified by three restriction endonucleases, then the vector pQE31-4CL 1 was transformed into expression host M15 (pREP4) and induced by isopropyl-a-D-thiogalactoside (IPTG) to express 60 kD fused protein Pt4CL1. The biologically active Pt4CL1, expressed as soluble protein, was achieved with 0.6 mmol'L-1 IPTG induction as the expression temperature declined from 37 to 28℃. The 6-His tag facilitates affinity binding to Ni^2+-nitrolotriacetic acid (NTA) and enables one-step purification to acquire the molecular SDS-PAGE electrophoresis purity of the active 4CL1 protein by agarose coupled with Ni^2+-NTA affinity chromatography. The optimal substrate for Pt4CL 1 was 4-coumarate.
文摘Coenzyme Q10(Co Q10) is an essential cofactor in the mitochondrial respiratory pathway and also functions as a lipid-soluble antioxidant. Co Q10 deficiency has been implicated in many clinical disorders and aging. Primary Co Q10 deficiency is a group of recessively inherited diseases caused by mutations in any gene involved in the Co Q10 biosynthesis pathway. Although primary Co Q10 deficiency is rare, its diagnosis is important because it is potentially treatable with exogenous Co Q10. Multiple system atrophy(MSA) was recently shown to be linked to mutations in the COQ2 gene, one of the genes involved in the Co Q10 biosynthesis pathway. MSA is relatively common in adult-onset neurodegenerative diseases characterized by Parkinsonism, cerebellar ataxia and autonomic failures. Because COQ2 mutations are associated with an increased risk of MSA, oral Co Q10 supplementation may be beneficial for MSA, as for other primary Co Q10 deficiencies. Statins are 3-hydroxy-3-methylglutaryl coenzyme A inhibitors that inhibit the biosynthesis of cholesterol, as well as the synthesis of mevalonate, a critical intermediate in cholesterol synthesis. Statin therapy has been associ-ated with a variety of muscle complaints from myalgia to rhabdomyolysis. Statin treatment carries a potential risk of Co Q10 deficiency, although no definite evidence has implicated CQ10 deficiency as the cause of statinrelated myopathy.
文摘<p style="margin-left:10.0pt;"> <br /> </p> <p style="margin-left:10.0pt;"> <span>The coenzyme B<sub>12</sub> dependent glutamate mutase is composed of two apoenzyme proteins subunits;S and E<sub>2</sub>, which while either fused or separate assemble with coenzyme B<sub>12</sub> to form an active holoenzyme (E<sub>2</sub>S<sub>2</sub>-B<sub>12</sub>) for catalyzing the reversible isomerization between (<i>S</i>)-glutamate and (2<i>S</i>, 3<i>S</i>)-3-methylas</span><span>- </span><span>partate. In order to assay the activity of glutamate mutase by UV spectrophotometry, this reaction is often coupled with methylaspartase which deaminates (2<i>S</i>, 3<i>S</i>)-3-methylaspartate to form mesaconate (<i>λ</i><sub>max</sub> = 240 nm, </span><span>Ɛ</span><sub><span>240</span></sub><span> = 3.8 mM<sup>-1</sup>·cm<sup>-1</sup>). The activities of different reconstitutions of glutamate mu<span>tase from separate apoenzyme components S and E in varied amount</span></span><span>s</span><span> of </span><span>coenzyme B<sub>12</sub> and adenosylpeptide B<sub>12</sub> as cofactors were measured by this assay and used to reveal the binding properties of the cofactor by the Michaelis</span><span>- </span><span>Menten Method. The values of <i>K<sub>m</sub></i> for coenzyme B<sub>12</sub> in due to reconstitutions of holoenzyme in 2, 7 and 14 S: E were determined as;1.12 ± 0.04 μM, 0.7 ± 0.05 μM and 0.52 ± 0.06 μM, respectively, so as those of adenosylpeptide B<sub>12</sub>;1.07 ± 0.04 μM and 0.35 ± 0.05 μM as obtained from respective 2 and 14 S: E compositions of holoenzyme. Analysis of these kinetics results curiously as<span>sociate</span></span><span>s</span><span> the increasing affinity of cofactors to apoenzyme with</span><span> </span><span>increased amount of component S used in reconstituting holoenzyme from separate</span><span> apoenzyme components and cofactor.</span><span> Moreover, in these studies a new method for assaying the activity of glutamate mutase was developed, whereby glutamate mutase activity is measured via depletion of NADH (<i>λ</i><sub>max</sub> = 340 nm, </span><span>Ɛ</span><sub><span>340</span></sub><span> = 6.3 mM<sup>-1</sup>·cm<sup>-1</sup>) as determined by UV spectrophotometry after addition of (2<i>S</i>,<span> 3<i>S</i>)-3-methylaspartate and pyruvate to a mixture of E<sub>2</sub>S<sub>2</sub>-B<sub>12</sub> and two auxiliary </span><span>holoenzymes system;pyridoxal-5-phosphate dependent glutamate-pyruvate </span><span>aminotransferase and N</span>ADH dependent (<i>R</i>)-2-hydroxyglutarate dehydrogenas<span>e. The activity of glutamate-pyruvate aminotransferase was relatively complete recovered upon the addition of (<i>S</i>)-glutamate and pyruvate to the mixtures of hologlutamate-pyruvate aminotransferase and (<i>R</i>)-2-hydroxylglutarate</span> dehydrogenase which were incubated with each putative inhibitor of glutamate mutase. Additionally, the new assay was used to determine the kinetic constants of (2<i>S</i>, 3<i>S</i>)-3-methylaspartate in the reaction of glutamate mutase as <i>K</i><sub>m</sub>= 7 ± 0.07 mM and <i>k</i><sub>cat</sub>= 0.54 ± 0.6 s<sup>-1</sup>. Application of Briggs-Haldane formula allowed the calculation of an equilibrium constant of the reversible isomerization, <i>K</i><sub>eq</sub> = [(<i>S</i>)-glutamate] × [(2<i>S</i>, 3<i>S</i>)-3-methylaspartate]<sup>-1</sup> = 16, where the kinetic constants of (<i>S</i>)-glutamate were determined by the standard methylaspartase coupled assay.<span></span></span> </p> <p> <br /> </p>
文摘Objective: To study the effect of levocarnitine + coenzyme Q10 adjuvant therapy on vasoactive molecules, endothelial injury and oxidative stress in patients with chronic heart failure. Methods: A total of 90 patients with chronic heart failure who were treated in the hospital between December 2014 and December 2016 were collected and divided into control group and observation group by random number table method, 45 cases in each group. Control group received conventional therapy, and observation group received levocarnitine + coenzyme Q10 adjuvant therapy on the basis of conventional therapy. The differences in vasoactive molecule, endothelial injury and oxidative stress levels were compared between the two groups before and after treatment. Results: Before treatment, the differences in vasoactive molecule, endothelial injury and oxidative stress levels were not statistically significant between the two groups of patients. After treatment, serum vasoactive molecules ET-1, AngⅡ and TXB2 contents of observation group were lower than those of control group while NO content was higher than that of control group;endothelial function indexes FMD level was higher than that of control group;serum oxidative stress indexes SOD and T-AOC contents were higher than those of control group while MDA and ROS contents were lower than those of control group. Conclusion: Levocarnitine + coenzyme Q10 adjuvant therapy can optimize the vascular activity, and reduce the endothelial injury and systemic oxidative stress response in patients with chronic heart failure.
文摘BACKGROUND Immune-mediated necrotizing myopathy is a rare autoimmune myopathy characterized by muscle weakness and elevated serum creatine kinase,with unique skeletal muscle pathology and magnetic resonance imaging features.CASE SUMMARY In this paper,two patients are reported:One was positive for anti-signal recognition particle antibody,and the other was positive for anti-3-hydroxy-3-methylglutaryl coenzyme A reductase antibody.CONCLUSION The clinical characteristics and treatment of the two patients were analysed,and the literature was reviewed to improve the recognition,diagnosis,and treatment of this disease.
基金This work was supported by the Japan Society for the Promotion of Science(JSPS)KAKENHI grants No.JP20K06074 to Y.I.and JP22K14830 to E.T.We sincerely thank Yuuki Kiya,Tomonori Masui,and Daigo Ogawa at Tokyo University of Technology for their technical support as well as Kenji Matsuura and the members of the Laboratory of Insect Ecology at Kyoto University for valuable suggestions and comments.We also thank our laboratory colleagues at Yamaguchi University and Tokyo University of Technology for their cooperation during this study.
文摘Termite queens and kings live longer than nonreproductive workers.Several molecular mechanisms contributing to their long lifespan have been investigated;however,the underlying biochemical explanation remains unclear.Coenzyme Q(CoQ),a component of the mitochondrial electron transport chain,plays an essential role in the lipophilic antioxidant defense system.Its beneficial effects on health and longevity have been well studied in several organisms.Herein,we demonstrated that long-lived termite queens have significantly higher levels of the lipophilic antioxidant CoQ_(10) than workers.Liquid chromatography analysis revealed that the levels of the reduced form of CoQ_(10) were 4 fold higher in the queen's body than in the worker's body.In addition,queens showed 7 fold higher levels of vitamin E,which plays a role in antilipid peroxidation along with CoQ,than workers.Furthermore,the oral administration of CoQ_(10) to termites increased the CoQ_(10) redox state in the body and their survival rate under oxidative stress.These findings suggest that CoQ_(10) acts as an efficient lipophilic antioxidant along with vitamin E in long-lived termite queens.This study provides essential biochemical and evolutionary insights into the relationship between CoQ_(10) concentrations and termite lifespan extension.
文摘Cholesterol plays several structural and metabolic roles that are vital for human biology. It spreads along the entire plasma membrane of the cell, modulating fluidity and concentrating in specialized sphingolipid-rich domains called rafts and caveolae. Cholesterol is also a substrate for steroid hormones. However, too much cholesterol can lead to pathological pictures such as atherosclerosis, which is a consequence of the accumu- lation of cholesterol into the cells of the artery wall. The liver is considered to be the metabolic power station of mammalians, where cholesterol homeostasis relies on an intricate network of cellular processes whose deregulations can lead to several life-threatening pathologies, such as familial and age-related hypercholesterolemia. Cholesterol homeostasis maintenance is carried out by: biosynthesis, via 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) activity; uptake, through low density lipoprotein receptors (LDLr); lipoprotein release in the blood; storage by esterification; and degradation and conversion into bile acids. Both HMGR and LDLr are transcribed as a function of cellular sterol amount by a family of transcription factors called sterol regulatory element binding proteins that are responsible for the maintenance of cholesterol homeostasis through an intricate mechanism of regulation. Cholesterol obtained by hepatic de novo synthesis can be esterified and incorporated into apolipoprotein B-100-containing very low density lipoproteins, which are then secreted into the bloodstream for transport to peripheral tissues. Moreover, dietary cholesterol is transferred from the intestine to the liver by high density lipoproteins (HDLs); all HDL particles are internalized in the liver, interacting with the hepatic scavenger receptor (SR-B1). Here we provide an updated overview of liver cholesterol metabolism regulation and deregulation and the causes of cholesterol metabolism-related diseases. Moreover, current pharmacological treatment and novel hypocho-lesterolemic strategies will also be introduced.
基金supported by the Key Program for International S&T Cooperation Projects of China(2016YFE0109000)the National Key R&D Program of China(2017YFF0211702)+1 种基金the National Natural Science Foundation of China(41475126 and 31802085)the Young Scientist Lifting Project,China(2017–2019)
文摘The objective of the present study was to examine the effect of different weaning methods on the ruminal methanogenic archaea composition and diversity in Holstein calves.Thirty-six newborn Holstein bull calves were assigned to 1 of 3 treatments:(1)conventional weaning(d 56)and fed a high proportion of solid feed(CWS);(2)conventional weaning(d 56)and fed a high proportion of liquid feed(CWL);(3)early weaning(d 42)and fed with a high proportion of solid feed(EWS).High-throughput sequencing of the methyl coenzyme M reductase(mcr A)gene,which encodes theα-subunit of methyl coenzyme M reductase-the enzyme that catalyzes the final step in methanogenesis was used to determine the composition and diversity of rumen methanogens.No significant difference(P>0.05)was observed for operational taxonomic units(OTUs)or richness indices,but diversity indices increased(P<0.05)for calves fed high dietary solids.Predominant families across the three treatments were Methanobacteriaceae,Thermoplasmataceae and Methanomassiliicoccaceae.Calves in the EWS treatment had a higher(P<0.05)relative abundance of Methanobrevibacter sp.strain AbM4 and Methanosphaera stadtmanae,while calves in the CWL treatment had a higher(P<0.05)abundance of Methanosphaera sp.strain SM9.A positive(P<0.05)relationship was identified between butyrate and Methanobrevibacter sp.strain AbM4.In conclusion,the composition and diversity of methanogens in the rumen of Holstein calves varied under the different weaning methods.This study identified a positive relationship between butyrate and Methanobrevibacter sp.strain AbM4,potentially reflecting correlations between ruminal fermentation variables and methanogenesis function.These in-depth analyses provide further understanding of weaning methods for intensified production systems.
文摘The Persian Gulf War of 1990 to 1991 involved the deployment of nearly 700,000 American troops to the Middle East.Deployment-related exposures to toxic substances such as pesticides,nerve agents,pyridostigmine bromide(PB),smoke from burning oil wells,and petrochemicals may have contributed to medical illness in as many as 250,000 of those American troops.The cluster of chronic symptoms,now referred to as Gulf War Illness(GWI),has been studied by many researchers over the past two decades.Although over$500 million has been spent on GWI research,to date,no cures or condition-specific treatments have been discovered,and the exact pathophysiology remains elusive.Using the 2007 National Institute of Health(NIH)Roadmap for Medical Research model as a reference framework,we reviewed studies of interventions involving GWI patients to assess the progress of treatment-related GWI research.All GWI clinical trial studies reviewed involved investigations of existing interventions that have shown efficacy in other diseases with analogous symptoms.After reviewing the published and ongoing registered clinical trials for cognitivebehavioral therapy,exercise therapy,acupuncture,coenzyme Q10(CoQ10),mifepristone,and carnosine in GWI patients,we identified only four treatments(cognitive-behavioral therapy,exercise therapy,CoQ10,and mifepristone)that have progressed beyond a phase II trial.We conclude that progress in the scientific study of therapies for GWI has not followed the NIH Roadmap for Medical Research model.Establishment of a standard case definition,prioritized GWI research funding for the characterization of the pathophysiology of the condition,and rapid replication and adaptation of early phase,single site clinical trials could substantially advance research progress and treatment discovery for this condition.
基金supported in part by a grant from NIHR01DC014437in part by the foundation of Science and Technology Commission of Shanghai Municipality (NO 15140900900)
文摘The imbalance of reactive oxygen species and antioxidants is considered to be an important factor in the cellular injury of the inner ear. At present, great attention has been placed on oxidative stress. However,little is known about fighting oxidative stress. In the current study, we evaluated antioxidant-induced cochlear damage by applying several different additional antioxidants. To determine whether excessive antioxidants can cause damage to cochlear cells, we treated cochlear explants with 50 m M M40403, a superoxide dismutase mimetic, 50 m M coenzyme Q-10, a vitamin-like antioxidant, or 50 m M d-methionine, an essential amino acid and the important antioxidant glutathione for 48 h. Control cochlear explants without the antioxidant treatment maintained their normal structures after incubation in the standard serum-free medium for 48 h, indicating the maintenance of the inherent oxidative and antioxidant balance in these cochlear explants. In contrast, M40403 and coenzyme Q-10-treated cochlear explants displayed significant hair cell damage together with slight damage to the auditory nerve fibers.Moreover, d-methiodine-treated explants exhibited severe damage to the surface structure of hair cells and the complete loss of the spiral ganglion neurons and their peripheral fibers. These results indicate that excessive antioxidants are detrimental to cochlear cells, suggesting that inappropriate dosages of antioxidant treatments can interrupt the balance of the inherent oxidative and antioxidant capacity in the cell.