Category: 624-49-7

Bose, Debdipta published the artcileImpact of disease-modifying therapies on MRI outcomes in patients with relapsing -remitting multiple sclerosis: A systematic review and network meta-analysis., Related Products of esters-buliding-blocks, the publication is Multiple sclerosis and related disorders (2022), 103760, database is MEDLINE.

BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune inflammatory demyelinating disorder of the central nervous system. The clinical presentation supported by characteristic findings on MRI forms the backbone of the current diagnostic criteria. This study was aimed to investigate the efficacy based on MRI outcomes of FDA approved disease-modifying therapies (DMTs) for relapsing-remitting MS (RRMS). MATERIALS AND METHODS: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCTs) of DMTs. The outcome measures were the mean number of T2 [new/enlarging lesions], new T1 [gadolinium-enhancing (Gd+) T1 and hypointense T1] lesions in brain MRI performed at 12 months or 24 months. We performed a network meta-analysis using the frequentist approach in STATA version 16.0. RESULTS: We identified 26 RCTs for final analysis. Interferon β-1a and placebo were the most common comparison treatment. Ocrelizumab was more effective in reducing the number of Gd+T1 lesions. Dimethyl fumarate 480 mg was relatively better in reducing the number of new T2 lesions. The treatment ranking showed that ocrelizumab and dimethyl fumarate 480 mg were more efficacious (1 and 0.9 in SUCRA, respectively) for reducing the number of new Gd+T1/hypointense lesions; dimethyl fumarate 480 mg/720 mg and natalizumab were more efficacious (1.0, 0.9 and 0.8 in SUCRA, respectively) to reduce the number of new T2 lesions. CONCLUSION: Ocrelizumab, dimethyl fumarate 480/720 mg and natalizumab demonstrated favourable MRI outcomes in patients with the RRMS.

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, Related Products of esters-buliding-blocks.

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

Zinger, Nicole published the artcileDimethyl Fumarate Reduces Inflammation in Chronic Active Multiple Sclerosis Lesions., Name: Dimethyl fumarate, the publication is Neurology(R) neuroimmunology & neuroinflammation (2022), 9(2), database is MEDLINE.

BACKGROUND AND OBJECTIVES: To determine the effects of dimethyl fumarate (DMF) and glatiramer acetate on iron content in chronic active lesions in patients with multiple sclerosis (MS) and in human microglia in vitro. METHODS: This was a retrospective observational study of 34 patients with relapsing-remitting MS and clinically isolated syndrome treated with DMF or glatiramer acetate. Patients had lesions with hyperintense rims on quantitative susceptibility mapping, were treated with DMF or glatiramer acetate (GA), and had a minimum of 2 on-treatment scans. Changes in susceptibility in rim lesions were compared among treatment groups in a linear mixed effects model. In a separate in vitro study, induced pluripotent stem cell-derived human microglia were treated with DMF or GA, and treatment-induced changes in iron content and activation state of microglia were compared. RESULTS: Rim lesions in patients treated with DMF had on average a 2.77-unit reduction in susceptibility per year over rim lesions in patients treated with GA (bootstrapped 95% CI -5.87 to -0.01), holding all other variables constant. Moreover, DMF but not GA reduced inflammatory activation and concomitantly iron content in human microglia in vitro. DISCUSSION: Together, our data indicate that DMF-induced reduction of susceptibility in MS lesions is associated with a decreased activation state in microglial cells. We have demonstrated that a specific disease modifying therapy, DMF, decreases glial activity in chronic active lesions. Susceptibility changes in rim lesions provide an in vivo biomarker for the effect of DMF on microglial activity. CLASSIFICATION OF EVIDENCE: This study provided Class III evidence that DMF is superior to GA in the presence of iron as a marker of inflammation as measured by MRI quantitative susceptibility mapping.

Neurology(R) neuroimmunology & neuroinflammation 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 C4H4Br2N2, Name: Dimethyl fumarate.

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

Sokolov, Alexey S. published the artcileGeneration of Cyclopentadiene for Diels-Alder Reactions by Visible-Light Irradiation of Iron Sandwich Complexes, Synthetic Route of 624-49-7, the publication is Helvetica Chimica Acta (2022), 105(4), e202100246, database is CAplus.

Cyclopentadienes readily undergo fast and selective Diels-Alder reactions which can be used for conjugation of biomols. and polymers. Herein authors present a new method for the photochem. generation of cyclopentadienes by the visible light irradiation of the iron complexes [(C₅H₄R)Fe(arene)]+. This reaction proceeds at room temperature, in water, and in the presence of potentially interfering amino acids. Free cyclopentadiene is trapped by dienophiles to give the corresponding Diels-Alder adducts in 72-95% yield.

Helvetica Chimica Acta 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 C22H12F6O6S2, Synthetic Route of 624-49-7.

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

Zhang, Lei published the artcileOxidase-Type C-H/C-H Coupling Using an Isoquinoline-Derived Organic Photocatalyst, Product Details of C6H8O4, the publication is Angewandte Chemie, International Edition (2022), 61(20), e202202649, database is CAplus and MEDLINE.

Herein, an isoquinoline-derived diaryl ketone-type photocatalyst I, which has much enhanced absorption of blue and visible light compared to conventional diaryl ketones was reported. This photocatalyst enables dehydrogenative cross-coupling of heteroarenes e.g., II with inactivated and activated alkanes viz. cyclohexane, THF, adamantane, etc. as well as aldehydes viz. propanal, pentanal, 3-methylbutanal, cyclopropanecarbaldehyde, cyclopentanecarbaldehyde using air as the oxidant. A wide range of heterocycles with various functional groups are suitable substrates. Transient absorption and excited-state quenching experiments point to an unconventional mechanism that involves an excited state ”self-quenching” process to generate the N-radical cation form of the sensitizer, which subsequently abstracts a hydrogen atom from the alkane substrate to yield a reactive alkyl radical.

Angewandte Chemie, International Edition 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 C10H6F17N, Product Details of C6H8O4.

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

Porwal, Mokshal H. published the artcileDisproportional increase in psoriasis reports in association with B cell depleting therapies in patients with multiple sclerosis, Application of Dimethyl fumarate, the publication is Multiple Sclerosis and Related Disorders (2022), 103832, database is CAplus and MEDLINE.

Some pathways involved in the pathogenesis of psoriasis share similarities with processes involved in multiple sclerosis (MS) pathogenesis. However, the association between MS and psoriasis is poorly understood. Since disease-modifying therapies for MS have various targets, it may be possible that the occurrence of psoriasis varies by drug. To analyze the frequency of psoriasis reports in patients treated with various disease-modifying therapies for MS. Data was collected using the FDA Adverse Event Reporting System (FAERS) and OpenFDA database between Jan. 2009 and June 2020. The study analyzed total reports of psoriasis out of total reports in the “Skin and S.c. Tissue Disorders” category for each drug and explored age, sex distribution, and report source. OpenFDA data was used to perform statistical analyses including reporting odds ratios (ROR) and information components. The study identified 517 psoriasis reports of 45,547 total skin and s.c. tissue disorders (1.13%) in FAERS. The highest proportions of reports in this study were associated with rituximab, ocrelizumab, and interferon beta 1a. The lowest proportion of reports were associated with glatiramer acetate, alemtuzumab, di-Me fumarate and teriflunomide. Reports of other autoimmune skin disorders were minimal (29 vitiligo, 33 pemphigoid, and 7 pemphigus). Patients primarily drove reports for most DMTs vs. healthcare providers. The proportion of reports from female patients were the highest for each DMT except alemtuzumab. OpenFDA query retrieved 302 total reports of psoriasis. Significantly increased reporting odds ratios (RORs, 95% confidence interval) of psoriasis were noted for rituximab (7.14, 3.92-13.00), ocrelizumab (3.79, 2.74-5.23), and fingolimod (1.33, 1.01-1.76). Significantly decreased RORs were noted for natalizumab (0.53, 0.36-0.80), glatiramer acetate (0.58, 0.35-0.96), and di-Me fumarate (0.71, 0.53-0.94). There are frequent reports of psoriasis in MS patients treated with various DMTs. However, reports and RORs were disproportionally high in association with B cell depleting therapies. Further research is required to determine if certain DMTs may serve as better options for individuals affected by, or at high-risk for developing psoriasis.

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, Application of Dimethyl fumarate.

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

Ntranos, Achilles published the artcileBacterial neurotoxic metabolites in multiple sclerosis cerebrospinal fluid and plasma., Category: esters-buliding-blocks, the publication is Brain : a journal of neurology (2022), 145(2), 569-583, database is MEDLINE.

The identification of intestinal dysbiosis in patients with neurological and psychiatric disorders has highlighted the importance of gut-brain communication, and yet the question regarding the identity of the components responsible for this cross-talk remains open. We previously reported that relapsing remitting multiple sclerosis patients treated with dimethyl fumarate have a prominent depletion of the gut microbiota, thereby suggesting that studying the composition of plasma and CSF samples from these patients may help to identify microbially derived metabolites. We used a functional xenogeneic assay consisting of cultured rat neurons exposed to CSF samples collected from multiple sclerosis patients before and after dimethyl fumarate treatment to assess neurotoxicity and then conducted a metabolomic analysis of plasma and CSF samples to identify metabolites with differential abundance. A weighted correlation network analysis allowed us to identify groups of metabolites, present in plasma and CSF samples, whose abundance correlated with the neurotoxic potential of the CSF. This analysis identified the presence of phenol and indole group metabolites of bacterial origin (e.g. p-cresol sulphate, indoxyl sulphate and N-phenylacetylglutamine) as potentially neurotoxic and decreased by treatment. Chronic exposure of cultured neurons to these metabolites impaired their firing rate and induced axonal damage, independent from mitochondrial dysfunction and oxidative stress, thereby identifying a novel pathway of neurotoxicity. Clinical, radiological and cognitive test metrics were also collected in treated patients at follow-up visits. Improved MRI metrics, disability and cognition were only detected in dimethyl fumarate-treated relapsing remitting multiple sclerosis patients. The levels of the identified metabolites of bacterial origin (p-cresol sulphate, indoxyl sulphate and N-phenylacetylglutamine) were inversely correlated to MRI measurements of cortical volume and directly correlated to the levels of neurofilament light chain, an established biomarker of neurodegeneration. Our data suggest that phenol and indole derivatives from the catabolism of tryptophan and phenylalanine are microbially derived metabolites, which may mediate gut-brain communication and induce neurotoxicity in multiple sclerosis.

Brain : a journal 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, Category: esters-buliding-blocks.

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

Park, Haesun published the artcileEvolution of drug delivery systems: From 1950 to 2020 and beyond, Related Products of esters-buliding-blocks, the publication is Journal of Controlled Release (2022), 53-65, database is CAplus and MEDLINE.

Modern drug delivery technol. began in 1952 with the advent of the Spansule sustained-release capsule technol., which can deliver a drug for 12 h after oral administration through an initial immediate dose followed by the remaining released gradually. Until the 1980s, oral and transdermal formulations providing therapeutic durations up to 24 h for small mols. dominated the drug delivery field and the market. The introduction of Lupron Depot in 1989 opened the door for long-acting injectables and implantables, extending the drug delivery duration from days to months and occasionally years. Notably, the new technologies allowed long-term delivery of peptide and protein drugs, although limited to parenteral administration. The introduction of the first PEGylated protein, Adagen, in 1990 marked the new era of PEGylation, resulting in Doxil (doxorubicin in PEGylated liposome) in 1995, Movantik (PEGylated naloxone – naloxegol) in 2014, and Onpattro (Patisiran – siRNA in PEGylated lipid nanoparticle) in 2018. Drug-polymer complexes were introduced, e.g., InFed (iron-dextran complex injection) in 1974 and Abraxane (paclitaxel-albumin complex) in 2005. In 2000, both Mylotarg (antibody-drug conjugate – gemtuzumab ozogamicin) and Rapamune (sirolimus nanocrystal formulation) were introduced. The year 2000 also marked the launching of the National Nanotechnol. Initiative by the U. S. government, which was soon followed by the rest of the world. Extensive work on nanomedicine, particularly formulations designed to escape from endosomes after being taken by tumor cells, along with PEGylation technol., ultimately resulted in the timely development of lipid nanoparticle formulations for COVID-19 vaccine delivery in 2020. While the advances in drug delivery technologies for the last seven decades are breathtaking, they are only the tip of an iceberg of technologies that have yet to be utilized in an approved formulation or even to be discovered. As life expectancy continues to increase, more people require long-term care for various diseases. Filling the current and future unmet needs requires innovative drug delivery technologies to overcome age-old familiar hurdles, e.g., improving water-solubility of poorly soluble drugs, overcoming biol. barriers, and developing more efficient long-acting depot formulations. The lessons learned from the past are essential assets for developing future drug delivery technologies implemented into products. As the development of COVID-19 vaccines demonstrated, meeting the unforeseen crisis of the uncertain future requires continuous cumulation of failures (as learning experiences), knowledge, and technologies. Conscious efforts of supporting diversified research topics in the drug delivery field are urgently needed more than ever.

Journal of Controlled Release 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, Related Products of esters-buliding-blocks.

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

Hoshino, Yasunobu published the artcileDysregulated B cell differentiation towards antibody-secreting cells in neuromyelitis optica spectrum disorder, Related Products of esters-buliding-blocks, the publication is Journal of Neuroinflammation (2022), 19(1), 6, database is CAplus and MEDLINE.

Anti-aquaporin 4 (AQP4) antibody (AQP4-Ab) is involved in the pathogenesis of neuromyelitis optica spectrum disorder (NMOSD). However, the mechanism involved in AQP4-Ab production remains unclear. We analyzed the immunophenotypes of patients with NMOSD and other neuroinflammatory diseases as well as healthy controls (HC) using flow cytometry. Transcriptome anal. of B cell subsets obtained from NMOSD patients and HCs was performed. The differentiation capacity of B cell subsets into antibody-secreting cells was analyzed. The frequencies of switched memory B (SMB) cells and plasmablasts were increased and that of naive B cells was decreased in NMOSD patients compared with relapsing-remitting multiple sclerosis patients and HC. SMB cells from NMOSD patients had an enhanced potential to differentiate into antibody-secreting cells when cocultured with T peripheral helper cells. Transcriptome anal. revealed that the profiles of B cell lineage transcription factors in NMOSD were skewed towards antibody-secreting cells and that IL-2 signaling was upregulated, particularly in naive B cells. Naive B cells expressing CD25, a receptor of IL-2, were increased in NMOSD patients and had a higher potential to differentiate into antibody-secreting cells, suggesting CD25+ naive B cells are committed to differentiate into antibody-secreting cells. To the best of our knowledge, this is the first study to demonstrate that B cells in NMOSD patients are abnormally skewed towards antibody-secreting cells at the transcriptome level during the early differentiation phase, and that IL-2 might participate in this pathogenic process. Our study indicates that CD25+ naive B cells are a novel candidate precursor of antibody-secreting cells in autoimmune diseases.

Journal of Neuroinflammation 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, Related Products of esters-buliding-blocks.

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

Shi, Fu-li published the artcileDimethyl fumarate ameliorates autoimmune hepatitis in mice by blocking NLRP3 inflammasome activation, Formula: C6H8O4, the publication is International Immunopharmacology (2022), 108867, database is CAplus and MEDLINE.

Di-Me fumarate (DMF) is a fumaric acid derivative clin. approved for the treatment of some inflammatory diseases, but the underlying mechanism for its therapeutic effects remains incompletely understood. NLR family pyrin domain containing 3 (NLRP3) inflammasome activation has critical roles in innate immune responses to various infections and sterile inflammations. In this study, we aimed to explore whether DMF affects auto-immune hepatitis (AIH) in mice induced by Con A (Con A) by modulating NLRP3 inflammasome activation. The results showed that DMF suppressed the activation of NLRP3 inflammasome activation in lipopolysaccharide-primed murine bone marrow-derived macrophages upon ATP or nigericin treatment, as evidenced by reduced cleavage of pro-caspase-1, release of mature interleukin-1β (IL-1β) and generation of gasdermin D N-terminal fragment (GSDMD-NT). DMF also greatly reduced ASC speck formation upon the stimulation of nigericin or ATP, indicating its inhibitory effect on NLRP3 inflammasome assembly. Consistent with reduced generation of GSDMD-NT, ATP or nigericin-induced pyroptosis was markedly suppressed by DMF. Moreover, DMF treatment alleviated mitochondrial damage induced by ATP or nigericin. Interestingly, all these effects were reversed by the protein kinase A (PKA) pathway inhibitors (H89 and MDL-12330A). Mechanistically, DMF enhanced PKA signaling and thus increased NLRP3 phosphorylation at PKA-specific sites to attenuate its activation. Importantly, DMF decreased serum levels of inflammatory cytokines and ameliorated liver injury in Con A-induced AIH of mice, concomitant with reduced the generation of caspase-1p10 and GSDMD-NT and alleviating mitochondrial aggregation in the liver. Collectively, DMF displayed anti-inflammatory effects by inhibiting NLRP3 inflammasome activation likely through regulating PKA signaling, highlighting its potential application in treating AIH.

International Immunopharmacology 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 C18H28B2O4, Formula: C6H8O4.

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

Moura, Joao published the artcileSARS-CoV-2 infection in patients with neuroimmunological disorders in a tertiary referral centre from the north of Portugal, HPLC of Formula: 624-49-7, the publication is Multiple Sclerosis and Related Disorders (2022), 103893, database is CAplus and MEDLINE.

The impact of COVID-19 in patients with neuroimmunol. disorders is not fully established. There is some evidence suggesting an increased risk of more severe infection associated with the use of immunosuppressors in this population. To characterize SARS-CoV-2 infection in patients followed in the neuroimmunol. outpatient clinic of a tertiary center from the north of Portugal. Retrospective anal. of neuroimmunol. patients with PCR-proven SARS-CoV-2 infection during the observational period of 20 mo. Ninety-one patients were infected, 68.1% female, with a mean age of 48.9±16.7 years. The median disease duration was 11.0 (IQR 6.0-19.0) years. Sixty-one patients (67.0%) had Multiple Sclerosis, of which 50 with relapsing-remitting course, 12 (13.2%) Myasthenia Gravis (MG), 6 (6.6%) Autoimmune Encephalitis and 6 (6.6%) Chronic Inflammatory Demyelinating Polyneuropathy. Seventy-six patients (83.5%) were taking disease-modifying therapy, 77.6% of which were on immunosuppressants, including anti-CD20 in 12 (13.2%). Most patients had mild COVID-19 (84.6%), with 3 cases (3.3%) of severe disease and, 7 cases (7.7%) of critical disease being reported. In total, 13 patients were hospitalized and 4 died. Patients with severe to critical disease were significantly older than patients with milder forms (69.4±21.0 vs. 46.5±14.4 years, p<0.01). MG was also associated with more severe disease (p=0.02). There was no association between comorbidities or use of immunosuppressors (including anti-CD20) and COVID-19 severity. Greater age and MG were associated with severe or critical COVID-19. We found no association between a specific DMT, including anti-CD20, and outcome. Clin. recovery was achieved by 93.4%.

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, HPLC of Formula: 624-49-7.

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