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Workshop report: Immunoassay standardisation for ?universal? influenza vaccines

The development of broadly reactive influenza vaccines raises the need to identify the most appropriate immunoassays that can be used for the evaluation of so-called universal influenza vaccines and to explore a path towards the standardisation of such assays. More than fifty experts from the global influenza vaccine research and development field met to initiate such discussion at a workshop co-organised by the EDUFLUVAC consortium, a European Union funded project coordinated by the European Vaccine Initiative, and the National Institutes of Health/National Institute of Allergy and Infectious Diseases, USA. The workshop audience agreed that it was not possible to establish a single immunoassay for ?universal? influenza vaccines because the current approaches differ in the vaccines’ nature and immunogenicity properties. Therefore, different scientific rationales for the immunoassay selection are required. To avoid dilution of efforts, the choice of the primary evaluation criteria (eg serological assays or T-cell assays) should drive the effort of harmonisation. However, at an early phase of clinical development, more efforts on exploratory assessments should be undertaken to better define the immune profile in response to immunisation with new vaccines. The workshop concluded that each laboratory should aim towards validation of the appropriate immunoassays used during the entire process of vaccine development from antigen discovery up to establishment of correlates of protection, including the different steps of quality control (eg potency assays), animal studies and human clinical development. Standardisation of the immunoassays is the ultimate goal, and there is a long way to go.

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N618 – PubChem

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Comparative genomics screen identifies microbe-associated molecular patterns from ?Candidatus Liberibacter? spp. That elicit immune responses in plants

Citrus huanglongbing (HLB), caused by phloem-limited ?Candidatus Liberibacter? bacteria, is a destructive disease threatening the worldwide citrus industry. The mechanisms of pathogenesis are poorly understood and no efficient strategy is available to control HLB. Here, we used a comparative genomics screen to identify candidate microbe-associated molecular patterns (MAMPs) from ?Ca. Liberibacter? spp. We identified the core genome from multiple ?Ca. Liberibacter? pathogens, and searched for core genes with signatures of positive selection. We hypothesized that genes encoding putative MAMPs would evolve to reduce recognition by the plant immune system, while retaining their essential functions. To efficiently screen candidate MAMP peptides, we established a high-throughput microtiter plate-based screening assay, particularly for citrus, that measured reactive oxygen species (ROS) production, which is a common immune response in plants. We found that two peptides could elicit ROS production in Arabidopsis and Nicotiana benthamiana. One of these peptides elicited ROS production and defense gene expression in HLB-tolerant citrus genotypes, and induced MAMP-triggered immunity against the bacterial pathogen Pseudomonas syringae. Our findings identify MAMPs that boost immunity in citrus and could help prevent or reduce HLB infection.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N539 – PubChem

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Inhibition of human liver aldehyde oxidase: Implications for potential drug-drug interactions

During the course of our research efforts to understand the kinetics of human aldehyde oxidase as a xenobiotic-clearing enzyme, we investigated the effect of eight different inhibitors on the oxidation of the probe substrate phthalazine. Saturation kinetic parameters for phthalazine oxidation in human liver cytosol were found to be the following: Km = 8.0 ¡À 0.4 muM and Vmax = 4.3 ¡À 0.1 nmol¡¤min -1¡¤mg protein-1. Inhibitory potency of the inhibitors tested ranged from 0.1 to 5 muM. Of the eight different inhibitor compounds tested, seven were observed to inhibit through a mixed mode and one through a strictly competitive mode. A ratio of the Kii and K is values was used to assess the relative competitiveness of each inhibitor. For the mixed inhibitors, the mode of inhibition varied from mostly uncompetitive to predominantly competitive (Kii/Kis values ranging from 0.1 to 15). The implications for potential drug-drug interactions and inhibition mechanism are discussed. We found two inhibitors, clozapine and chlorpromazine, that have a moderate predicted risk of drug-drug interactions based on the Ki value relative to the inhibitor concentration in human plasma, having a calculated [I]/Ki value of 0.4 and 0.8, respectively. Copyright

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Phthalazine – Wikipedia,
Phthalazine | C8H6N55 – PubChem

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Visible-light-mediated Minisci C-H alkylation of heteroarenes with unactivated alkyl halides using O2 as an oxidant

Herein, we report a protocol for direct visible-light-mediated Minisci C-H alkylation of heteroarenes with unactivated alkyl halides using molecular oxygen as an oxidant at room temperature. This mild protocol is compatible with a wide array of sensitive functional groups and has a broad substrate scope. Notably, functionalization of (iso)quinolines, pyridines, phenanthrolines, quinazoline, and other heterocyclic compounds with unactivated primary, secondary, and tertiary alkyl halides proceeds smoothly under the standard conditions. The robustness of this protocol is further demonstrated by the late-stage functionalization of complex nitrogen-containing natural products and drugs.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N128 – PubChem

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Synthesis of new analogs of 3-methyl-[1,2,4] triazolo [3,4-a] phthalazines via Suzuki coupling and evaluation of their anticancer and antimicrobial activity

A series of new N-aryl substituted phenyl acetamide analogs of 3-methyl-[1,2,4] triazolo[3,4-a] phthalazines were synthesized starting from commercially available, in-expensive phthalic anhydride in good yields (65-75 %) via Suzuki Coupling. These compounds were tested for inhibition activity against HCT 116 cancer cell line by using MIT assay. Among the library of compounds, N-(3-methoxyphenyl)-2-(4-(3-methyl-[1,2,4]triazolo[3,4-a]phthalazin-6-yl)phenyl) acetamide followed by 2-(4-(3-methyl-[1,2,4]triazolo[3,4-a]phthalazin-6-yl)phenyl)-N-(m-tolyl) acetamide and N-(3-chlorophenyl)-2-(4-(3-methyl-[1,2,4]triazolo[3,4-a]phthalazin-6-yl)phenyl) acetamide were found to be active compounds with IC50 of 70 to and 90 mug mL-1. Further, the compounds were also screened for their antimicrobial activities.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N244 – PubChem

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Chemiluminescence properties of luminol related o-hydroxybenzimidazole analogues: Experimental and DFT based approach to photophysical properties

Novel luminol-isoluminol derivatives containing o-hydroxyphenyl benzimidazole unit were synthesized from aromatic aldehydes and diaminophthalates followed by heating under reflux with hydrazine hydrate. The chemiluminescent properties were studied in hydrogen peroxide, potassium hexacyanoferrate(III) and sodium hydroxide solution. The chemiluminescence properties were compared with the standard luminol and isoluminol systems it was observed that the chemiluminescence properties of the novel derivatives were superior to luminol and isoluminol. Density Functional Theory computations have been used in order to have a greater understanding of the structural, molecular, electronic and photophysical properties. The experimental absorption and emission wavelength values were in good agreement with the computed vertical excitation and emission values.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N122 – PubChem

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Impact of Bariatric Surgical Intervention on Peripheral Blood Neutrophil (PBN) Function in Obesity

Aim: The aim of this study was to investigate the impact of weight loss following gastric band surgery on multiple measures of peripheral blood neutrophil (PBN) function. Material and Methods: Twenty-three obese patients undergoing gastric band surgery were recruited to a longitudinal intervention study, alongside non-obese, healthy gender- and age-matched controls. Eighteen pairs of patients and controls completed all stages of the study. PBNs were isolated by density centrifugation and a comprehensive analysis of PBN function was undertaken at various stages of the patients? bariatric surgical care pathway. Results: Obese patients exhibited exaggerated PBN activity in response to various stimuli, characterised by higher reactive oxygen species (ROS) generation (n = 18, p < 0.001) and release of pro-inflammatory cytokines (n = 10, p < 0.05) and lower PBN extracellular trap (NET) formation (n = 18, p < 0.01). PBN chemotactic accuracy was also impaired prior to surgery (n = 18, p < 0.01). Weight loss was associated with normalised NET production and lower ROS production and cytokine release relative to healthy controls. However, chemotactic accuracy remained impaired in patients. Conclusions: Weight loss following gastric band surgery was associated with a decrease in the pro-inflammatory activities of peripheral blood neutrophils (PBNs). A hyper-inflammatory PBN phenotype, involving excess ROS and cytokine release, reduced NET formation and chemotaxis, may lead to a reduced ability to eliminate infection, alongside inflammation-mediated tissue damage in obese individuals. A reaction mechanism is the microscopic path by which reactants are transformed into products. Each step is an elementary reaction. In my other articles, you can also check out more blogs about 3682-14-2 Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N627 – PubChem

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Recent advances in the preparation and application of organic? inorganic hybrid magnetic nanocatalysts on multicomponent reactions

The combination of advantages of multicomponent reactions (MCRs) and magnetic nano catalysts is going to be an emerging and strategic area and is an ideal blend for the development of sustainable methodologies in organic synthesis in green and benign media. This review focuses on the synthesis, functionalization, and application of organic-inorganic hybrid magnetic nanoparticles as novel task-specific catalysts on multicomponent reactions (MCRs) in recent years. So, properly magnetic nanoparticles can be used as building blocks for the fabrication of various functional moieties, and their application in catalysis of MCRs will be briefly reviewed. The heterogenization of the catalyst using magnetic nanoparticles allows it to be recovered and reused using an external magnet. The approach to magnetic separation is not only easy, cost-effective, favorable for work-up procedures and industrial applications, but also is usually more effective than filtration or centrifugation as it diminishes the loss of the catalyst.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N77 – PubChem

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Anti-HIV activity of stilbene-related heterocyclic compounds

Viral transcription has not been routinely targeted in the development of new antiviral drugs. This crucial step of the viral cycle depends on the concerted action of cellular and viral proteins such as NF-kappaB and Tat. In the present study, stilbene-related heterocyclic compounds including benzalphthalide, phthalazinone, imidazoindole and pyrimidoisoindole derivatives are tested for their anti-HIV activity. Original assays based on recombinant viruses were used to evaluate HIV replication inhibition and stably transfected cell lines were used to evaluate inhibition of Tat and NF-kappaB proteins. Some of the stilbene-related heterocyclic compounds analysed displayed anti-HIV activity through interference with NF-kappaB and Tat function. Moreover, compounds inhibiting both targets displayed a stronger activity on viral replication.

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N721 – PubChem

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Current immunoassay methods and their applications to clinically used biomarkers of breast cancer

Breast cancer is the leading cause of cancer-related mortality worldwide, with a higher incidence in developed countries. The biomarkers for breast cancer such as estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, CA (cancer antigen) 15-3, CA 27.29, and carcinoembryonic antigen have been recommended for use in the laboratory based on the guidelines of American and European societies. Immunoassays have been frequently and consistently used to detect these clinically established biomarkers of breast cancer. Despite the higher accessibility of serum biomarkers, including CA 15-3, CA 27.29, and CEA, compared to tissue markers, variations in immunoassays affect their standardization and clinical utility. When reviewing the immunoassays used to detect these serum markers, we found that the most frequently used immunoassay was enzyme-linked immunosorbent assay, followed by electrochemiluminescent immunoassay, and then chemiluminescence immunoassay for CA 15-3 and CEA. Meanwhile, the chemiluminescence immunoassay was the most common technique for CA27.29. The electrochemiluminescent immunoassay and monoclonal fluorometric assay have become the preferred methods in 2010?2019 compared to 2000?2009. Analytical and clinical performance factors such as sensitivity, specificity, detection limit, hazard risk to laboratory personnel, speed, and economic feasibility influenced these changes in user preference. When using the immunoassays, there should be a comprehensive understanding of the principles, advantages, vulnerability, and precautions for interpretation. In the future, a combination of immunological biomarkers and genetic platforms will benefit patients with breast cancer by facilitating prognosis prediction and guiding therapeutic intervention.

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N580 – PubChem