Category: 58-97-9

Ghobrial, Carolyne; Sobhy, Rodina; Mogahed, Engy; Abdullatif, Hala; El-Karaksy, Hanaa published the artcile< Is sofosbuvir/ledipasvir safe for the hearts of children with hepatitis C virus>, Name: ((2R,3S,4R,5R)-5-(2,4-Dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl dihydrogen phosphate, the main research area is hepatitis C virus infection heart sofosbuvir ledipasvir safety child; Bradycardia; ECG; HCV; Sofosbuvir.

Symptomatic bradycardia has been reported in adults treated for chronic hepatitis C using sofosbuvir based regimens.We studied the cardiac safety of sofosbuvir/ledipasvir in Egyptian children, treated for chronic hepatitis C. The study included 40 hepatitis C virus infected children and adolescents 12-17 years old, using the combination of sofosbuvir (400 mg)/ledipasvir (90 mg) in a single oral tablet (Harvoni) taken daily for 12 wk. All subjects underwent a baseline standard 12-lead surface Electrocardiog. that was repeated at 4 and 12 wk of therapy. Electrocardiog. parameters (Heart Rate, RR interval, PR interval, QRS, QT interval, corrected QT interval, QT dispersion, JT interval, corrected JT interval, JT dispersion, Tpeak-Tend interval) were compared at the 3 different time points during antiviral therapy.No symptoms related to the cardiovascular system were reported during treatment. There were no cases of symptomatic bradycardia/syncope. Heart rate was noted to be significantly lower and RR and QT intervals were significantly longer in the baseline electrocardiog. Heart rate was significantly lower and RR interval was significantly longer in patients with higher viral load.No adverse cardiovascular events were observed in this group of HCV infected children and adolescents treated with sofosbuvir/ledipasvir. None of the patients developed bradyarrhythmias during treatment.

Digestive and Liver Disease published new progress about Adolescent, mammalian. 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, Name: ((2R,3S,4R,5R)-5-(2,4-Dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl dihydrogen phosphate.

Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

Agustina Toscanini, M.; Belen Favarolo, M.; Luis Gonzalez Flecha, F.; Ebert, Berit; Rautengarten, Carsten; Bredeston, Luis M. published the artcile< Conserved Glu-47 and Lys-50 residues are critical for UDP-N-acetylglucosamine/UMP antiport activity of the mouse Golgi-associated transporter Slc35a3>, COA of Formula: C9H13N2O9P, the main research area is UDPGlcNAc UDP N acetylglucosamine UMP transporter; mouse Golgi associated transporter Slc35a3; Golgi; UDP-GlcNAc metabolism; antiporter; congenital glycosylation disorder; glycoprotein biosynthesis; membrane protein; membrane transport; secretory pathway; solute carrier family 35 member A3 (SLC35A3); structural model.

Nucleotide sugar transporters (NSTs) regulate the flux of activated sugars from the cytosol into the lumen of the Golgi apparatus where glycosyltransferases use them for the modification of proteins, lipids, and proteoglycans. It has been well-established that NSTs are antiporters that exchange nucleotide sugars with the resp. nucleoside monophosphate. Nevertheless, information about the mol. basis of ligand recognition and transport is scarce. Here, using topol. predictors, cysteine-scanning mutagenesis, expression of GFP-tagged protein variants, and phenotypic complementation of the yeast strain Kl3, we identified residues involved in the activity of a mouse UDP-GlcNAc transporter, murine solute carrier family 35 member A3 (mSlc35a3). We specifically focused on the putative transmembrane helix 2 (TMH2) and observed that cells expressing E47C or K50C mSlc35a3 variants had lower levels of GlcNAc-containing glycoconjugates than WT cells, indicating impaired UDP-GlcNAc transport activity of these two variants. A conservative substitution anal. revealed that single or double substitutions of Glu-47 and Lys-50 do not restore GlcNAc glycoconjugates. Anal. of mSlc35a3 and its genetic variants reconstituted into proteoliposomes disclosed the following: (i) all variants act as UDP-GlcNAc/UMP antiporters; (ii) conservative substitutions (E47D, E47Q, K50R, or K50H) impair UDP-GlcNAc uptake; and (iii) substitutions of Glu-47 and Lys-50 dramatically alter kinetic parameters, consistent with a critical role of these two residues in mSlc35a3 function. A bioinformatics anal. revealed that an EXXK motif in TMH2 is highly conserved across SLC35 A subfamily members, and a 3D-homol. model predicted that Glu-47 and Lys-50 are facing the central cavity of the protein.

Journal of Biological Chemistry published new progress about Golgi apparatus. 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, COA of Formula: C9H13N2O9P.

Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

Schwarz, Kathleen B.; Rosenthal, Philip; Murray, Karen F.; Honegger, Jonathan R.; Hardikar, Winita; Hague, Rosie; Mittal, Naveen; Massetto, Benedetta; Brainard, Diana M.; Hsueh, Chia-Hsiang; Shao, Jiang; Parhy, Bandita; Narkewicz, Michael R.; Rao, Girish S.; Whitworth, Suzanne; Bansal, Sanjay; Balistreri, William F. published the artcile< Ledipasvir-Sofosbuvir for 12 Weeks in Children 3 to <6 Years Old With Chronic Hepatitis C>, COA of Formula: C9H13N2O9P, the main research area is chronic hepatitis C infection ledipasvir sofosbuvir efficacy safety.

For children under 12 years of age who have chronic HCV infection, there are currently no approved treatments with direct-acting antiviral agents. We therefore evaluated the safety and efficacy of ledipasvir-sofosbuvir in HCV-infected children aged 3 to <6 years. In an open-label study, patients 3 to <6 years old chronically infected with HCV genotype 1 (n = 33) or 4 (n = 1) received weight-based doses of combined ledipasvir-sofosbuvir as granules (33.75 mg/150 mg for weights <17 kg or 45 mg/200 mg for weights =17 kg) for 12 wk. The primary endpoint was sustained virol. response 12 wk after treatment (SVR12). For the first 14 patients, intensive pharmacokinetic sampling was done on day 10 of treatment. All patients had been infected through perinatal transmission and were treatment naive. No patients had known cirrhosis. Ten patients (29%) weighed <17 kg. SVR12 was achieved in 97% of patients (33 of 34); the patient who did not achieve SVR12 was 3 years old and discontinued treatment after 5 days because of an adverse event ""abnormal drug taste. "" The most common adverse events were vomiting (24% of patients), cough (21%), and pyrexia (21%). No patients experienced a serious adverse event. Intensive pharmacokinetic anal. of 13 patients for whom data were evaluable confirmed that the doses selected were appropriate. Conclusion: Ledipasvir-sofosbuvir was well tolerated and highly effective in children 3 to <6 years old with chronic HCV infection. Hepatology (Hoboken, NJ, United States) published new progress about Child. 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, COA of Formula: C9H13N2O9P.

Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

Angiolilli, Chiara; Leijten, Emmerik F. A.; Bekker, Cornelis P. J.; Eeftink, Ella; Giovannone, Barbara; Nordkamp, Michel Olde; van der Wal, Marlot; Thijs, Judith L.; Vastert, Sebastiaan J.; van Wijk, Femke; Radstake, Timothy R. D. J.; van Loosdregt, Jorg published the artcile< ZFP36 Family Members Regulate the Proinflammatory Features of Psoriatic Dermal Fibroblasts>, Formula: C9H13N2O9P, the main research area is zinc finger protein psoriatic dermal fibroblast proinflammatory feature.

Dermal fibroblasts are strategically positioned underneath the basal epidermis layer to support keratinocyte proliferation and extracellular matrix production In inflammatory conditions, these fibroblasts produce cytokines and chemokines that promote the chemoattraction of immune cells into the dermis and the hyperplasia of the epidermis, two characteristic hallmarks of psoriasis. However, how dermal fibroblasts specifically contribute to psoriasis development remains largely uncharacterized. In this study, we investigated through which cytokines and signaling pathways dermal fibroblasts contribute to the inflammatory features of psoriatic skin. We show that dermal fibroblasts from lesional psoriatic skin are important producers of inflammatory mediators, including IL-6, CXCL8, and CXCL2. This increased cytokine production was found to be regulated by ZFP36 family members ZFP36, ZFP36L1, and ZFP36L2, RNA-binding proteins with mRNA-degrading properties. In addition, the expression of ZFP36 family proteins was found to be reduced in chronic inflammatory conditions that mimic psoriatic lesional skin. Collectively, these results indicate that dermal fibroblasts are important producers of cytokines in psoriatic skin and that reduced expression of ZFP36 members in psoriasis dermal fibroblasts contributes to their inflammatory phenotype.

Journal of Investigative Dermatology published new progress about Animal gene Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (BHLHE4). 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, Formula: C9H13N2O9P.

Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

Babatin, Mohammed A; AlGhamdi, Abdullah S; Assiri, Abdullah M; AlBiladi, Haziz; AlOthmani, Hammad S; Mogharbel, Mohammed H; Mahallawi, Wedad; Asselah, Tarik; Sanai, Faisal M published the artcile< Treatment efficacy of ledipasvir/sofosbuvir for 8 weeks in non-cirrhotic chronic hepatitis C genotype 4 patients.>, Recommanded Product: ((2R,3S,4R,5R)-5-(2,4-Dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl dihydrogen phosphate, the main research area is Duration; genotype 4; hepatitis C; ledipasvir; sofosbuvir.

BACKGROUND/AIMS: Ledipasvir/sofosbuvir (LDV/SOF) combination is administered for 12 to 24 weeks to treat hepatitis C virus (HCV); guidelines recommend 8 weeks treatment duration for HCV genotype (GT) 1 infection based on the patient’s baseline characteristics. Data on treating HCV GT4 with LDV/SOF are limited. In this prospective cohort study, the efficacy and safety of 8 weeks treatment duration with LDV/SOF was evaluated in HCV GT4 patients in Saudi Arabia. PATIENTS AND METHODS: Treatment-naïve, non-cirrhotic HCV GT4 patients received LDV/SOF for 8 weeks. HCV RNA levels and laboratory evaluations were recorded at baseline and at Weeks 4, 8, and 20. The primary endpoint was sustained virologic response 12 weeks after the end of the treatment (SVR12). Safety data were also recorded. RESULTS: Forty-five patients with a mean age of 43.9 ± 17.2 years participated, of whom 57.8% were male. Mean log10HCV RNA was 6.26 ± 6.32 IU/mL and most (91.1%) had baseline HCV RNA levels <6 million IU/mL. The most frequent comorbidities were hypertension and diabetes mellitus (20.0% each). Concomitant medication was taken by 18 patients (40.0%), of whom two took proton pump inhibitors. Overall, SVR12 was 97.8% (95% confidence interval [CI]: 88.2%-99.9%); one patient (2.2%) relapsed post treatment. No serious adverse events or discontinuations were reported. Eighteen patients (44.4%) had 38 adverse events related to LDV/SOF; the most frequent was headache. CONCLUSIONS: An 8-week regimen of LDV/SOF was well tolerated and efficacious in this treatment-naïve, non-cirrhotic HCV GT4-infected population. This study provides valuable information on a short treatment regimen for HCV GT4 infection in a real-world setting. Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association published new progress about 58-97-9. 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, Recommanded Product: ((2R,3S,4R,5R)-5-(2,4-Dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl dihydrogen phosphate.

Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

Yang, Lutong; Guo, Zhiheng; Yu, Miao; Cai, Xiaokun; Mao, Yingyi; Tian, Fang; Xu, Wenhui; Liu, Guoliang; Li, Xiang; Zhao, Yanrong; Xie, Lin published the artcile< Profile of Nucleotides in Chinese Mature Breast Milk from Six Regions>, Product Details of C9H13N2O9P, the main research area is mature breast milk nucleotides profile chinese; MUAI; breast milk; nucleotides; total potentially available nucleosides.

This study measured the total potentially available nucleoside (TPAN) content in breast milk from six different regions of China as a part of the Maternal Nutrition and Infant Investigation (MUAI) study. A total of 631 breast milk samples were collected from healthy, lactating women with singleton, full-term pregnancies between 40 and 45 days postpartum in Changchun, Chengdu, Lanzhou, Shanghai, Tianjin, and Guangzhou. TPAN and free 5′-monophosphate nucleotide (5′-MNT) contents were determined by high-performance liquid chromatog. The TPAN content of the Chinese mature milk ranged from 11.61 mg/L to 111.09 mg/L, with a median level of 43.26 mg/L. Four types of nucleotides were identified, and the median levels of cytidine monophosphate (CMP), uridine monophosphate (UMP), guanosine monophosphate (GMP), and adenosine monophosphate (AMP) were 22.84 mg/L, 9.37 mg/L, 4.86 mg/L, and 4.80 mg/L, resp. CMP was the predominant nucleotide, accounting for 52.9% of the TPAN content, while free 5′-MNT accounted for 18.38% of the TPAN content. The distribution pattern of the TPAN content and level of the individual nucleotides were significantly different among the selected regions (p < 0.05), but the result showed no significant differences in the TPAN level in breast milk (p > 0.05). In addition, no correlation was reported between the geog. distribution and TPAN levels. This result showed that TPAN better reflects the level of total potential nucleosides in Chinese breast milk rather than 5′-MNT in free form. CMP, UMP, GMP, and AMP are the only 4 types of nucleotides reported in all detections. In addition, results revealed a large variation of TPAN levels in Chinese breast milk across six regions, so that the median value may not be the optimal fortification level of TPAN for Chinese infant populations.

Nutrients published new progress about Age groups. 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, Product Details of C9H13N2O9P.

Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

Buvelot, He Lene; Roth, Myriam; Jaquet, Vincent; Lozkhin, Andrey; Renzoni, Adriana; Bonetti, Eve-Julie; Gaia, Nadia; Laumay, Floriane; Mollin, Michele; Stasia, Marie-Jose; Schrenzel, Jacques; Franc ois, Patrice; Krause, Karl-Heinz published the artcile< Hydrogen peroxide affects growth of S. aureus through downregulation of genes involved in pyrimidine biosynthesis>, Reference of 58-97-9, the main research area is hydrogen peroxide carA pyrimidine Staphylococcus; S. aureus; carA; hydrogen peroxide; neutrophils; pyrimidine metabolism.

Reactive oxygen species (ROS) play a crucial role in the cellular defense against S. aureus, as evidenced by the importance of this pathogen in patients lacking the ROS-generating phagocyte NADPH oxidase NOX2. ROS concentrations required to kill S. aureusin vitro are much higher than those found in the phagosome. We therefore hypothesized that sublethal ROS concentrations may play a role in S. aureus gene dysregulation and investigated the in vitro transcriptomic response of S. aureus to sublethal concentrations of hydrogen peroxide (H2O2). A striking observation of these experiments was a coordinated and massive downregulation of genes involved in pyrimidine metabolism Using transposon insertion mutants, we demonstrated that deletion of carA, a gene involved in pyrimidine synthesis, led to a significant growth defect and to an increased sensitivity of S. aureus to added H2O2. The phenotype of the carA mutant could be reversed through supplementation with the pyrimidine precursor uracil, or with a multicopy vector encoding carA. As opposed to the impact of ROS on extracellular survival, carA deletion did not affect the intracellular survival in neutrophils. Our results raise the possibility that ROS-dependent downregulation of pyrimidine metabolism might be a survival strategy of S. aureus, allowing colonization through intracellular survival, while decreasing the risk of killing the host through dampened extracellular growth.

Frontiers in Immunology published new progress about Homo sapiens. 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, Reference of 58-97-9.

Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

Vieux, Karl-Frederic; Prothro, Katherine P.; Kelley, Leanne H.; Palmer, Cameron; Maine, Eleanor M.; Veksler-Lublinsky, Isana; McJunkin, Katherine published the artcile< Screening by deep sequencing reveals mediators of microRNA tailing in C. elegans>, Application of C9H13N2O9P, the main research area is microRNA TUT4 TUT7 CDE1 Candida.

MicroRNAs are frequently modified by addition of untemplated nucleotides to the 3′ end, but the role of this tailing is often unclear. Here we characterize the prevalence and functional consequences of microRNA tailing in vivo, using Caenorhabditis elegans. MicroRNA tailing in C. elegans consists mostly of mono-uridylation of mature microRNA species, with rarer mono-adenylation which is likely added to microRNA precursors. Through a targeted RNAi screen, we discover that the TUT4/TUT7 gene family member CID-1/CDE-1/PUP-1 is required for uridylation, whereas the GLD2 gene family member F31C3.2-here named GLD-2-related 2 (GLDR-2)-is required for adenylation. Thus, the TUT4/TUT7 and GLD2 gene families have broadly conserved roles in miRNA modification. We specifically examine the role of tailing in microRNA turnover. We determine half-lives of microRNAs after acute inactivation of microRNA biogenesis, revealing that half-lives are generally long (median = 20.7 h), as observed in other systems. Although we observe that the proportion of tailed species increases over time after biogenesis, disrupting tailing does not alter microRNA decay. Thus, tailing is not a global regulator of decay in C. elegans. Nonetheless, by identifying the responsible enzymes, this study lays the groundwork to explore whether tailing plays more specialized context- or miRNA-specific regulatory roles.

Nucleic Acids Research published new progress about Animal gene Role: BSU (Biological Study, Unclassified), PRP (Properties), BIOL (Biological Study) (GLD2). 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, Application of C9H13N2O9P.

Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

Adeline, Naomi Joan Faray; Geue, Claudia; Hermami, Mohsen Rezaei published the artcile< Cost-effectiveness of treating hepatitis C in Seychelles.>, Application of C9H13N2O9P, the main research area is Hepatitis C; cost-effectiveness; direct-acting antiviral.

INTRODUCTION: approximately eighty million people around the world are living with hepatitis C, and 700,000 people die every year, due to hepatitis C related complications. In Seychelles, a total of 777 cases of hepatitis C were reported from 2002 to 2016, but up to mid of 2016, the cases were not being treated. Treatment with Harvoni, a combination of sofosbuvir and ledipasvir (SOF/LDV), is now being offered on the condition that the patient does not, or has stopped, injecting drugs. This paper is the first to establish the cost effectiveness of treating all cases of hepatitis C in Seychelles with Harvoni, as compared to no treatment. METHODS: data extracted from literature was used to populate an economic model to calculate cost-effectiveness from Seychelles’ government perspective. The model structure was also informed by the systematic review and an accompanying grading of economic models using the Consolidated Health Economic Evaluation Reporting Standard (CHEERS) checklist. A Markov model was developed, employing a lifetime horizon and costs and benefits were analysed from a payer’s perspective and combined into incremental cost effectiveness ratios (ICERs). RESULTS: the direct-acting antiviral (DAA), Harvoni, was found to be cost-saving in Seychelles hepatitis C virus (HCV) cohort, as compared to no treatment, with an ICER of € 753.65/QALY. The treatment was also cost-saving when stratified by gender, with the ICER of male and female being € 783.74/QALY and € 635.20/QALY, respectively. Moreover, the results obtained from acceptability curves showed that treating patients with Harvoni is the most cost-effective option, even for low thresholds. CONCLUSION: treating hepatitis C cases in Seychelles is cost-saving. It is worth developing a treatment programme to include all cases of hepatitis C, regardless of status of drug injection.

The Pan African medical journal published new progress about 58-97-9. 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, Application of C9H13N2O9P.

Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem

Hassenkam, Tue; Deamer, David published the artcile< Visualizing RNA polymers produced by hot wet-dry cycling>, SDS of cas: 58-97-9, the main research area is RNA polymers hot wet dry cycling.

It is possible that the transition from abiotic systems to life relied on RNA polymers that served as ribozyme-like catalysts and for storing genetic information. The source of such polymers is uncertain, but previous investigations reported that wet-dry cycles simulating prebiotic hot springs provide sufficient energy to drive condensation reactions of mononucleotides to form oligomers and polymers. The aim of the study reported here was to verify this claim and visualize the products prepared from solutions composed of single mononucleotides and 1:1 mixture of two mononucleotides. Therefore, we designed experiments that allowed comparisons of all such mixtures representing six combinations of the four mononucleotides of RNA. We observed irregular stringy patches and crystal strands when wet-dry cycling was performed at room temperature (20°C). However, when the same solutions were exposed to wet-dry cycles at 80°C, we observed what appeared to be true polymers. Their thickness was consistent with RNA-like products composed of covalently bonded monomers, while irregular strings and crystal segments of mononucleotides dried or cycled at room temperature were consistent with structures assembled and stabilized by weak hydrogen bonds. In a few instances we observed rings with short polymer attachments. These observations are consistent with previous claims of polymerization during wet-dry cycling. We conclude that RNA-like polymers and rings could have been synthesized non-enzymically in freshwater hot springs on the prebiotic Earth with sizes sufficient to fold into ribozymes and genetic mols. required for life to begin.

Scientific Reports published new progress about Crystallinity. 58-97-9 belongs to class tetrahydrofurans, and the molecular formula is C9H13N2O9P, SDS of cas: 58-97-9.

Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem