Category: 624-49-7

Diebold, Martin published the artcileImmunological Predictors of Dimethyl Fumarate-Induced Lymphopenia, Product Details of C6H8O4, the publication is Annals of Neurology (2022), 91(5), 676-681, database is CAplus and MEDLINE.

Treatment with di-Me fumarate (DMF) leads to lymphopenia and infectious complications in a subset of patients with multiple sclerosis (MS). Here, we aimed to reveal immune markers of DMF-associated lymphopenia. This prospective observational study longitudinally assessed 31 individuals with MS by single-cell mass cytometry before and after 12 and 48 wk of DMF therapy. Employing a neural network-based representation learning approach, we identified a CCR4-expressing T helper cell population neg. associated with relevant lymphopenia. CCR4-expressing T helper cells represent a candidate prognostic biomarker for the development of relevant lymphopenia in patients undergoing DMF treatment.

Annals of Neurology published new progress about 624-49-7. 624-49-7 belongs to esters-buliding-blocks, auxiliary class Inhibitor,Natural product, name is Dimethyl fumarate, and the molecular formula is C6H8O4, Product Details of C6H8O4.

Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics

Diebold, Martin published the artcileHigh-dimensional immune profiling identifies a biomarker to monitor dimethyl fumarate response in multiple sclerosis, Computed Properties of 624-49-7, the publication is Proceedings of the National Academy of Sciences of the United States of America (2022), 119(31), e2205042119, database is CAplus and MEDLINE.

Di-Me fumarate (DMF) is an immunomodulatory treatment for multiple sclerosis (MS). Despite its wide clin. use, the mechanisms underlying clin. response are not understood. This study aimed to reveal immune markers of therapeutic response to DMF treatment in MS. For this purpose, we prospectively collected peripheral blood mononuclear cells (PBMCs) from a highly characterized cohort of 44 individuals with MS before and at 12 and 48 wk of DMF treatment. Single cells were profiled using high-dimensional mass cytometry. To capture the heterogeneity of different immune subsets, we adopted a bioinformatic multipanel approach that allowed cell population-cluster assignment of more than 50 different parameters, including lineage and activation markers as well as chemokine receptors and cytokines. Data were further analyzed in a semiunbiased fashion implementing a supervised representation learning approach to capture subtle longitudinal immune changes characteristic for therapy response. With this approach, we identified a population of memory T helper cells expressing high levels of neuroinflammatory cytokines (granulocyte-macrophage colony-stimulating factor [GM-CSF], interferon γ [IFNγ]) as well as CXCR3, whose abundance correlated with treatment response. Using spectral flow cytometry, we confirmed these findings in a second cohort of patients. Serum neurofilament light-chain levels confirmed the correlation of this immune cell signature with axonal damage. The identified cell population is expanded in peripheral blood under natalizumab treatment, substantiating a specific role in treatment response. We propose that depletion of GM-CSF-, IFNγ-, and CXCR3-expressing T helper cells is the main mechanism of action of DMF and allows monitoring of treatment response.

Proceedings of the National Academy of Sciences of the United States of America published new progress about 624-49-7. 624-49-7 belongs to esters-buliding-blocks, auxiliary class Inhibitor,Natural product, name is Dimethyl fumarate, and the molecular formula is C6H8O4, Computed Properties of 624-49-7.

Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics

Liu, Hengrui published the artcileCharacterization of a patient-derived variant of GPX4 for precision therapy, Product Details of C6H8O4, the publication is Nature Chemical Biology (2022), 18(1), 91-100, database is CAplus and MEDLINE.

Glutathione peroxidase 4 (GPX4), as the only enzyme in mammals capable of reducing esterified phospholipid hydroperoxides within a cellular context, protects cells from ferroptosis. We identified a homozygous point mutation in the GPX4 gene, resulting in an R152H coding mutation, in three patients with Sedaghatian-type spondylometaphyseal dysplasia. Using structure-based analyses and cell models, including patient fibroblasts, of this variant, we found that the missense variant destabilized a critical loop, which disrupted the active site and caused a substantial loss of enzymic function. We also found that the R152H variant of GPX4 is less susceptible to degradation, revealing the degradation mechanism of the GPX4 protein. Proof-of-concept therapeutic treatments, which overcome the impaired R152H GPX4 activity, including selenium supplementation, selective antioxidants and a deuterated polyunsaturated fatty acid were identified. In addition to revealing a general approach to investigating rare genetic diseases, we demonstrate the biochem. foundations of therapeutic strategies targeting GPX4.

Nature Chemical Biology published new progress about 624-49-7. 624-49-7 belongs to esters-buliding-blocks, auxiliary class Inhibitor,Natural product, name is Dimethyl fumarate, and the molecular formula is C6H8O4, Product Details of C6H8O4.

Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics

Portaccio, Emilio published the artcileImpact of COVID-19 on multiple sclerosis care and management: Results from the European Committee for Treatment and Research in Multiple Sclerosis survey, Safety of Dimethyl fumarate, the publication is Multiple Sclerosis Journal (2022), 28(1), 132-138, database is CAplus and MEDLINE.

Background:: The spread of Coronavirus disease-19 (COVID-19) poses unique challenges in the management of people with multiple sclerosis (PwMS). Objectives:: To collect data about the impact of COVID-19 emergency on access to care for PwMS and on MS treatment practices. Methods:: Between March and July 2020, the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) promoted an online survey covering patient access to care, management of relapses and visits, disease-modifying therapy (DMT) and experience with COVID-19. Results:: Three-hundred and sixty neurologists from 52 countries (68from Europe) completed the survey. 98reported COVID-19-related restrictions. Telemedicine was adopted to overcome the limited access to care and was newly activated (73) or widely implemented (17). 70reported changes in DMT management. Interferons and glatiramer were considered safe. No modifications were considered for natalizumab in 64, cladribine in 24, anti-CD20 in 22and alemtuzumab in 17; 18(for alemtuzumab and cladribine) and 43(for anti-CD20) considered postponing treatment. Conclusion:: The ECTRIMS survey highlighted the challenges in keeping standards of care in clin. practice. Telemedicine clearly needs to be implemented. Gathering data on DMT safety will remain crucial to inform treatment decisions.

Multiple Sclerosis Journal published new progress about 624-49-7. 624-49-7 belongs to esters-buliding-blocks, auxiliary class Inhibitor,Natural product, name is Dimethyl fumarate, and the molecular formula is C6H8O4, Safety of Dimethyl fumarate.

Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics

Maniscalco, Giorgia Teresa published the artcileLong term persistence of SARS-CoV-2 humoral response in multiple sclerosis subjects, SDS of cas: 624-49-7, the publication is Multiple Sclerosis and Related Disorders (2022), 103800, database is CAplus and MEDLINE.

The persistence of the severe acute respiratory syndrome coronavirus (SARS-CoV)-2 pandemic, partly due to the appearance of highly infectious variants, has made booster vaccinations necessary for vulnerable groups. Here, we present data regarding the decline of the SARS-CoV-2 BNT162b2 mRNA vaccine-induced humoral immune response in a monocentric cohort of MS patients.96 MS patients undergoing eight different DMTs, all without previous SARS-CoV-2 infection, were evaluated for anti-Spike IgG levels, 21 days (T1) and 5-6 mo (T2) after the second SARS-CoV-2 BNT162b2 mRNA vaccine dose. The anti-Spike IgG titer from MS subjects was compared with 21 age- and sex-matched healthy controls (HC). When compared with SARS-CoV-2 IgG levels at T2 in HC, we observed comparable levels in interferon-β 1a-, di-Me fumarate-, teriflunomide- and natalizumab-treated MS subjects, but an impaired humoral response in MS subjects undergoing glatiramer acetate-, cladribine-, fingolimod- and ocrelizumab-treatments. Moreover, comparison between SARS-CoV-2 IgG Spike titer at T1 and T2 revealed a faster decline of the humoral response in patients undergoing di-Me fumarate-, interferon-β 1a- and glatiramer acetate-therapies, while those receiving teriflunomide and natalizumab showed higher persistence compared to healthy controls. The prominent decline in humoral response in MS subjects undergoing di-Me fumarate-, interferon-β 1a- and glatiramer acetate-therapies should be considered when formulating booster regimens as these subjects would benefit of early booster vaccinations.

Multiple Sclerosis and Related Disorders published new progress about 624-49-7. 624-49-7 belongs to esters-buliding-blocks, auxiliary class Inhibitor,Natural product, name is Dimethyl fumarate, and the molecular formula is C6H8O4, SDS of cas: 624-49-7.

Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics

Wang, Yi published the artcileDiscovery of SARS-CoV-2-E channel inhibitors as antiviral candidates, Product Details of C6H8O4, the publication is Acta Pharmacologica Sinica (2022), 43(4), 781-787, database is CAplus and MEDLINE.

Abstract: Lack of efficiency has been a major problem shared by all currently developed anti-SARS-CoV-2 therapies. Our previous study shows that SARS-CoV-2 structural envelope (2-E) protein forms a type of cation channel, and heterogeneously expression of 2-E channels causes host cell death. In this study we developed a cell-based high throughput screening (HTS) assay and used it to discover inhibitors against 2-E channels. Among 4376 compounds tested, 34 hits with cell protection activity were found. Followed by an anti-viral anal., 15 compounds which could inhibit SARS-CoV-2 replication were identified. In electrophysiol. experiments, three representatives showing inhibitory effect on 2-E channels were chosen for further characterization. Among them, proanthocyanidins directly bound to 2-E channel with binding affinity (K_D) of 22.14 μM in surface plasmon resonance assay. Mol. modeling and docking anal. revealed that proanthocyanidins inserted into the pore of 2-E N-terminal vestibule acting as a channel blocker. Consistently, mutations of Glu 8 and Asn 15, two residues lining the proposed binding pocket, abolished the inhibitory effects of proanthocyanidins. The natural product proanthocyanidins are widely used as cosmetic, suggesting a potential of proanthocyanidins as disinfectant for external use. This study further demonstrates that 2-E channel is an effective antiviral drug target and provides a potential antiviral candidate against SARS-CoV-2.

Acta Pharmacologica Sinica published new progress about 624-49-7. 624-49-7 belongs to esters-buliding-blocks, auxiliary class Inhibitor,Natural product, name is Dimethyl fumarate, and the molecular formula is C7H7IN2O, Product Details of C6H8O4.

Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics

Valenca, Helber da Maia published the artcileBeneficial effects of Ilex paraguariensis in the prevention of obesity-associated metabolic disorders in mice, Formula: C6H8O4, the publication is Phytotherapy Research (2022), 36(2), 1032-1042, database is CAplus and MEDLINE.

Obesity is a chronic condition involving inflammation and oxidative stress that commonly predisposes affected individuals to develop metabolic disorders. We hypothesize that Ilex paraguariensis (IP) can modulate oxidative stress and inflammation underpinning metabolic disorders caused by obesity. C57BL/6 mice were fed a high-fat diet (HFD group) for 12 wk. Concomitantly, some mice were treated with roasted IP (15 mg/mL – HFD + IP) or di-Me fumarate (DMF) as a pos. control (2 mg/mL – HFD + DMF). The control group received standard chow and water ad libitum. Histol. analyses of fat tissue and liver, and quantification of mediators related to oxidative stress (Kelch-like ECH-associated protein 1/NF-E2-related factor 2, NADP(H) quinone oxidoreductase-1 [NQO1], heme oxygenase 1 [HO1], and superoxide dismutase) as well as metabolic profile blood biomarkers (glucose, leptin, resistin, high-d. lipoproteins [HDLs], and triglycerides) were performed. Metabolic disorders were prevented in mice treated with IP, as evidenced by the observation that glucose, HDL, and resistin levels were similar to those assessed in the control group. Morphol. analyses showed that both IP and DMF treatments prevented hepatic steatosis and adipocyte hypertrophy in visceral adipose tissue. Finally, although the antioxidant response stimulated by IP was quite limited, significant effects were found on NQO1 and HO1 expression. In conclusion, IP has promising preventative effects on the development of metabolic disorders caused by obesity.

Phytotherapy Research published new progress about 624-49-7. 624-49-7 belongs to esters-buliding-blocks, auxiliary class Inhibitor,Natural product, name is Dimethyl fumarate, and the molecular formula is C3H6O2, Formula: C6H8O4.

Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics

Vainio, S. K. published the artcileDimethyl fumarate decreases short-term but not long-term inflammation in a focal EAE model of neuroinflammation, Name: Dimethyl fumarate, the publication is EJNMMI Research (2022), 12(1), 6, database is CAplus and MEDLINE.

Abstract: Background: Di-Me fumarate (DMF) is an oral immunomodulatory drug used in the treatment of autoimmune diseases. Here, we sought to study whether the effect of DMF can be detected using positron emission tomog. (PET) targeting the 18-kDa translocator protein (TSPO) in the focal delayed-type hypersensitivity rat model of multiple sclerosis (fDTH-EAE). The rats were treated orally twice daily from lesion activation (day 0) with either vehicle (tap water with 0.08% Methocel, 200μL; control group n = 4 (3 after week four)) or 15 mg/kg DMF (n = 4) in 0.08% aqueous Methocel (200μL) for 8 wk. The animals were imaged by PET using the TSPO tracer [¹⁸F]GE-180 in weeks 0, 1, 2, 4, 8, and 18 following lesion activation, and the non-displaceable binding potential (BP_ND) was calculated Immunohistochem. staining for Iba1, CD4, and CD8 was performed in week 18, and in sep. cohorts of animals, following 2 or 4 wk of treatment. Results: Using the fDTH-EAE model, DMF reduced the [¹⁸F]GE-180 BP_ND in the DMF-treated animals compared to control animals after 1 wk of treatment (two-tailed unpaired t test, p = 0.031), but not in weeks 2, 4, 8, or 18 when imaged in vivo by PET. Immunostaining for Iba1 showed that DMF had no effect on the perilesional volume or the core lesion volume after 2 or 4 wk of treatment, or at 18 wk. However, the optical d. (OD) measurements of CD4⁺ staining showed reduced OD in the lesions of the treated rats. Conclusions: DMF reduced the microglial activation in the fDTH-EAE model after 1 wk of treatment, as detected by PET imaging of the TSPO ligand [¹⁸F]GE-180. However, over an extended time course, reduced microglial activation was not observed using [¹⁸F]GE-180 or by immunohistochem. for Iba1⁺ microglia/macrophages. Addnl., DMF did affect the infiltration of CD4⁺ and CD8⁺ T-lymphocytes at the fDTH-EAE lesion.

EJNMMI Research published new progress about 624-49-7. 624-49-7 belongs to esters-buliding-blocks, auxiliary class Inhibitor,Natural product, name is Dimethyl fumarate, and the molecular formula is C18H16N2O6, Name: Dimethyl fumarate.

Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics

Lu, Hongyu published the artcileSynergistic degradation of fluorene in soil by dielectric barrier discharge plasma combined with P25/NH₂-MIL-125(Ti), HPLC of Formula: 624-49-7, the publication is Chemosphere (2022), 133950, database is CAplus and MEDLINE.

Plasma techniques to degrade pollutants are generally more efficient than conventional methods, but exist some problems such as high energy consumption, incomplete degradation of pollutants, and secondary pollution caused by highly toxic intermediates. In this study, the dielec. barrier discharge plasma (DBDP) combined with the Ti-based metal organic frameworks (MOFs) catalysts (P25/NH₂-MIL-125(Ti)) was used to degrade fluorene in the soil. The synergistic treatment technique used in soil remediation can realize a green and promising treatment efficiency with relatively low energy consumption. Compared with DBDP system alone, the synergetic treatment system of DBDP and P25/NH₂-MIL-125(Ti) considerably increased the degradation efficiency of fluorene in the soil to above 90% at 10 min, even with a relatively low discharge voltage (5 kV). The synergistic treatment system achieved 88.8% of fluorene mineralization at 60 min. Optical emission spectroscopy and ESR spectroscopy both showed that •OH and •O₂^– played an important role in the synergetic treatment system. Nine main intermediates were identified using gas chromatog.-mass spectrometry and Fourier transform IR anal. The main degradation of fluorine in soil was caused by the electronic transition of the catalytic material excited by DBDP, and finally mineralized into CO₂ and H₂O. The fluorene and its toxic intermediates were effectively removed. This study provides an insight for achieving high efficiency and environmentally friendly application perspective in soil remediation.

Chemosphere published new progress about 624-49-7. 624-49-7 belongs to esters-buliding-blocks, auxiliary class Inhibitor,Natural product, name is Dimethyl fumarate, and the molecular formula is C6H8O4, HPLC of Formula: 624-49-7.

Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics

Bosco-Levy, Pauline published the artcileComparative effectiveness of dimethyl fumarate in multiple sclerosis, SDS of cas: 624-49-7, the publication is British Journal of Clinical Pharmacology (2022), 88(3), 1268-1278, database is CAplus and MEDLINE.

To assess the effectiveness of di-Me fumarate (DMF) on annual rate of relapse subject to treatment (ARRt) and disability progression in multiple sclerosis (MS) compared to injectable immunomodulators (IMM), teriflunomide (TERI) and fingolimob (FTY), in real-life setting. A population-based cohort study was conducted using data of the French nationwide claims database, SNDS. All patients initiating IMM, TERI, FTY or DMF between 1 July 2015 and 12 Dec. 2017, with 4.5 years of database history and 1-3.5 years of follow-up were included in this study. DMF patients were 1:1 matched to IMM, TERI or FTY using a high dimensional propensity score. Neg. binomial regression and a logistic regression model were used to estimate the relative risk (RR ± [95% CI]) of ARRt and the odds ratio (OR ± [95% CI]) of disability progression, resp. Overall, 9304 subjects were identified: 29.0% initiated DMF, 33.2% TERI, 5.6% FTY and 32.2% an IMM. The matched cohorts consisted of 1779 DMF-IMM patients, 1679 DMF-TERI patients, and 376 DMF-FTY patients. DMF significantly reduced ARRt compared to IMM (RR 0.72 [0.61-0.86]) and TERI (0.81 [0.68-0.96]) and did not show any significant difference when compared with FTY. The risk of the progression of MS-specific disability was not significantly different for any matched cohorts. DMF is associated with lower risk of treated relapse for patients with RRMS than other first-line RRMS agents (TERI and IIM).

British Journal of Clinical Pharmacology published new progress about 624-49-7. 624-49-7 belongs to esters-buliding-blocks, auxiliary class Inhibitor,Natural product, name is Dimethyl fumarate, and the molecular formula is C6H8O4, SDS of cas: 624-49-7.

Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics