Author: tianli

Lewis, Matthew T. published the artcileSkeletal muscle energetics are compromised only during high-intensity contractions in the Goto-Kakizaki rat model of type 2 diabetes, Category: alcohols-buliding-blocks, the main research area is type 2 diabetes skeletal muscle energetic contraction; hyperglycemia; inactivity; insulin resistance; mitochondrial oxidative phosphorylation; obesity.

Type 2 diabetes (T2D) presents with hyperglycemia and insulin resistance, affecting over 30 million people in the United States alone. Previous work has hypothesized that mitochondria are dysfunctional in T2D and results in both reduced ATP production and glucose disposal. However, a direct link between mitochondrial function and T2D has not been determined In the current study, the Goto-Kakizaki (GK) rat model of T2D was used to quantify mitochondrial function in vitro and in vivo over a broad range of contraction-induced metabolic workloads. During high-frequency sciatic nerve stimulation, hindlimb muscle contractions at 2- and 4-Hz intensities, the GK rat failed to maintain similar bioenergetic steady states to Wistar control (WC) rats measured by phosphorus magnetic resonance spectroscopy, despite similar force production Mitochondria isolated from muscles of GK and WC rats also showed no difference in mitochondrial ATP production capacity in vitro, measured by high-resolution respirometry. At lower intensities (0.25-1 Hz) there were no detectable differences between GK and WC rats in sustained energy balance. There were similar phosphocreatine concentrations during steady-state contraction and postcontractile recovery (τ = 72 ± 6 s GK vs. 71 ± 2 s WC). Taken together, these results suggest that deficiencies in skeletal muscle energetics seen at higher intensities are not due to mitochondrial dysfunction in the GK rat.

American Journal of Physiology published new progress about Body mass index. 97-67-6 belongs to class alcohols-buliding-blocks, name is (S)-2-hydroxysuccinic acid, and the molecular formula is C4H6O5, Category: alcohols-buliding-blocks.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Fisher, Gordon published the artcileSex and race contribute to variation in mitochondrial function and insulin sensitivity, Related Products of alcohols-buliding-blocks, the main research area is skeletal muscle myofiber insulin hydrogen peroxide; insulin sensitivity; mitochondrial function; race; reactive oxygen species; sex.

Insulin sensitivity is lower in African American (AA) vs. Caucasian American (CA). We tested the hypothesis that lower insulin sensitivity in AA could be explained by mitochondrial respiratory rates, coupling efficiency, myofiber composition, or H2O2 emission. A secondary aim was to determine whether sex affected the results. AA and CA men and women, 19-45 years, BMI 17-43 kg m2, were assessed for insulin sensitivity (SIClamp) using a euglycemic clamp at 120 mU/m2/min, muscle mitochondrial function using high-resolution respirometry, H2O2 emission using amplex red, and % myofiber composition SIClamp was greater in CA (p < 0.01) and women (p < 0.01). Proportion of type I myofibers was lower in AA (p < 0.01). Mitochondrial respiratory rates, coupling efficiency, and H2O2 production did not differ with race. Mitochondrial function was pos. associated with insulin sensitivity in women but not men. Statistical adjustment for mitochondrial function, H2O2 production, or fiber composition did not eliminate the race difference in SIClamp. Neither mitochondrial respiratory rates, coupling efficiency, myofiber composition, nor mitochondrial reactive oxygen species production explained lower SIClamp in AA compared to CA. The source of lower insulin sensitivity in AA may be due to other aspects of skeletal muscle that have yet to be identified. Physiological Reports published new progress about Body mass index. 97-67-6 belongs to class alcohols-buliding-blocks, name is (S)-2-hydroxysuccinic acid, and the molecular formula is C4H6O5, Related Products of alcohols-buliding-blocks.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Zou, Kai published the artcileAltered tricarboxylic acid cycle flux in primary myotubes from severely obese humans, Related Products of alcohols-buliding-blocks, the main research area is severe obesity primary myotube tricarboxylic acid cycle flux glucose.

Background/objective: The partitioning of glucose toward glycolytic end products rather than glucose oxidation and glycogen storage is evident in skeletal muscle with severe obesity and type 2 diabetes. The purpose of the present study was to determine the possible mechanism by which severe obesity alters insulin-mediated glucose partitioning in human skeletal muscle. Subjects/methods: Primary human skeletal muscle cells (HSkMC) were isolated from lean (BMI = 23.6 ± 2.6 kg/m2, n = 9) and severely obese (BMI = 48.8 ± 1.9 kg/m2, n = 8) female subjects. Glucose oxidation, glycogen synthesis, non-oxidized glycolysis, pyruvate oxidation, and targeted TCA cycle metabolomics were examined in differentiated myotubes under basal and insulin-stimulated conditions. Results: Myotubes derived from severely obese subjects exhibited attenuated response of glycogen synthesis (20.3%; 95% CI [4.7, 28.8]; P = 0.017) and glucose oxidation (5.6%; 95% CI [0.3, 8.6]; P = 0.046) with a concomitant greater increase (23.8%; 95% CI [5.7, 47.8]; P = 0.004) in non-oxidized glycolytic end products with insulin stimulation in comparison to the lean group (34.2% [24.9, 45.1]; 13.1% [8.6, 16.4], and 2.9% [-4.1, 12.2], resp.). These obesity-related alterations in glucose partitioning appeared to be linked with reduced TCA cycle flux, as 2-[14C]-pyruvate oxidation (358.4 pmol/mg protein/min [303.7, 432.9] vs. lean 439.2 pmol/mg protein/min [393.6, 463.1]; P = 0.013) along with several TCA cycle intermediates, were suppressed in the skeletal muscle of severely obese individuals. Conclusions: These data suggest that with severe obesity the partitioning of glucose toward anaerobic glycolysis in response to insulin is a resilient characteristic of human skeletal muscle. This altered glucose partitioning appeared to be due, at least in part, to a reduction in TCA cycle flux.

International Journal of Obesity published new progress about Body mass index. 97-67-6 belongs to class alcohols-buliding-blocks, name is (S)-2-hydroxysuccinic acid, and the molecular formula is C4H6O5, Related Products of alcohols-buliding-blocks.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Loh, Fan Siew published the artcileInsecticidal properties of Citrus hystrix DC leaves essential oil against Spodoptera litura fabricius, Application of 2-(2-Hydroxypropan-2-yl)-5-methylcyclohexanol, the main research area is Citrus essential oil insecticide Spodoptera.

Chem. anal. by gas chromatog. (GC) and gas chromatog.-mass spectroscopy (GC-MS) revealed presence of 29 compounds in the essential oil fraction of kaffir lime, Citrus hystrix fresh leaves. Beta-citronellal was the major compound present with 66.85% of total oil followed by beta-citronellol (6.59%), linalool (3.90%) and citronellol (1.76%). Insecticidal properties of C. hystrix leaves essential oil was investigated against tobacco army worm, Spodoptera litura using topical application bioassay on uniform weighted second instar larvae in the laboratory Essential oil was effective in killing the larvae and showed that the LD50 is 26.748 μL/g. Insect development and growth index observations showed that the essential oil had antifeedant properties resulting in severe growth inhibition of S. litura.

Journal of Medicinal Plants Research published new progress about Bioinsecticides. 42822-86-6 belongs to class alcohols-buliding-blocks, name is 2-(2-Hydroxypropan-2-yl)-5-methylcyclohexanol, and the molecular formula is C10H20O2, Application of 2-(2-Hydroxypropan-2-yl)-5-methylcyclohexanol.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Ndindayino, F. published the artcileBioavailability of hydrochlorothiazide from isomalt-based moulded tablets, Application of (3R,4R,5R)-6-(((2S,3R,4S,5S,6R)-3,4,5-Trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)hexane-1,2,3,4,5-pentaol, the main research area is hydrochlorothiazide isomalt molded tablet bioavailability.

The bioavailability of hydrochlorothiazide (HCT) from molded isomalt-based tablets was evaluated after oral administration of 50 mg HCT to healthy volunteers as an oral molded tablet and as a lozenge, in comparison with a conventional tablet formulation (Dichlotride® 50 mg). Molded tablets had a high relative bioavailability (Frel) as the pharmacokinetic parameters (Cmax, tmax, t1/2, AUC0 24 h) determined from HCT plasma concentration vs. time profiles were not significantly different (P>0.05; two-way ANOVA) in comparison with the conventional tablet. The relative bioavailability of the molded tablet administered as a lozenge and as an oral tablet was 106.2±30.9% and 89.4±25.9%, resp., in relation to the conventional tablet formulation. Direct molding of isomalt tablets proved to be a suitable technique to administer a poorly soluble drug either as a conventional tablet or as a lozenge.

International Journal of Pharmaceutics published new progress about Bioavailability. 64519-82-0 belongs to class alcohols-buliding-blocks, name is (3R,4R,5R)-6-(((2S,3R,4S,5S,6R)-3,4,5-Trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)hexane-1,2,3,4,5-pentaol, and the molecular formula is C12H24O11, Application of (3R,4R,5R)-6-(((2S,3R,4S,5S,6R)-3,4,5-Trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)hexane-1,2,3,4,5-pentaol.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Alkhalidi, Bashar A. published the artcileClarithromycin laurate salt: physicochemical properties and pharmacokinetics after oral administration in humans, Category: alcohols-buliding-blocks, the main research area is clarithromycin laurate salt tablet oral drug delivery pharmacokinetics; Clarithromycin laurate; bioavailability; fatty acid salt; physicochemical characterization.

To prepare and characterize the physicochem. and pharmacokinetic properties of clarithromycin laurate (CLM-L), a fatty acid salt of clarithromycin (CLM). CLM-L was prepared by a simple co-melting process. The formation of CLM-L was confirmed using FTIR, 1H NMR, and 13C NMR. Solubility, intrinsic dissolution rate (IDR), and partitioning properties of CLM-L were determined and compared to those of CLM. Bioavailability of CLM from CLM-L tablets was evaluated in healthy volunteers and compared to immediate release CLM tablets. CLM-L showed lower aqueous solubility, higher partitioning coefficient, and slower dissolution rate. Tablets of CLM-L also showed a significantly slower in vitro release in comparison to CLM tablets. Cmax, Tmax and AUC0→inf of CLM-L tablets and immediate release CLM tablets did not show a significant difference. However, the AUC0→inf for the CLM-L tablets tended to be higher than that of CLM tablets at all-time points. CLM-L was successfully prepared and its formation was confirmed. CLM-L was more hydrophobic than CLM. It exhibited a slight in vivo absorption enhancement in comparison to CLM. However, its pharmacokinetic behavior was comparable to that of CLM.

Pharmaceutical Development and Technology published new progress about Bioavailability. 111-87-5 belongs to class alcohols-buliding-blocks, name is n-Octanol, and the molecular formula is C8H18O, Category: alcohols-buliding-blocks.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Shao, Liangyu published the artcileEffects of Borneol on the Release of Compound Danshen Colon-Specific Osmotic Pump Capsule In Vitro and Pharmacokinetics Study in Beagle Dogs, Synthetic Route of 124-76-5, the main research area is borneol compound danshen colon osmotic pump capsule pharmacokinetics dog; borneol; colon-specific osmotic pump capsule; compound Danshen; in vitro release; in vivo pharmacokinetics.

Borneol can enhance the bioavailability of several other drugs by opening the blood-brain barrier and inhibiting P-glycoprotein (P-gp) efflux. However, whether borneol will impact the bioavailability and the mechanism of compound Danshen colon-specific osmotic pump capsule (CDCOPC) remains unclear. This study aimed to determine the effects of borneol on the in vitro release and in vivo pharmacokinetic characteristics of CDCOPC. Besides, the in vitro release behavior of CDCOPC was further assessed by chromatog. fingerprints. The in vitro release studies showed that borneol followed the zero-order release and hardly impacted the in vitro release of Salvia miltiorrhiza and Panax notoginseng in CDCOPC. Moreover, as revealed from the similarity results of fingerprints, the in vitro release of different components of CDCOPC was almost simultaneous. Compared with the com. available tablets, the pharmacokinetics studies suggested that both CDCOPCs containing and lacking borneol could significantly prolong the retention time of these effective components; their average relative bioavailability values increased to 448.70% and 350.97%, resp. Notably, borneol significantly improved the relative bioavailability of some components of CDCOPC, such as salvianolic acid B (SAB), tanshinone IIA (Tan IIA), notoginsenoside R1 (R1), ginsenoside Rg1 (Rg1), and ginsenoside Re (Re) from CDCOPC, while it slightly impacted ginsenoside Rb1 (Rb1) and ginsenoside Rd (Rd). Summarily, borneol is capable of improving the bioavailability of some effective components in CDCOPC, which is critical to design with CDCOPC for enhanced bioavailability. This study could also help reveal the composition principle of the compound Danshen formula (CDF).

AAPS PharmSciTech published new progress about Bioavailability. 124-76-5 belongs to class alcohols-buliding-blocks, name is rel-(1R,2R,4R)-1,7,7-Trimethylbicyclo[2.2.1]heptan-2-ol, and the molecular formula is C10H18O, Synthetic Route of 124-76-5.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Almadiy, Abdulrhman A. published the artcileBioactivity of Deverra tortuosa essential oil, its nanoemulsion, and phenylpropanoids against the cowpea weevil, a stored grain pest with eco-toxicological evaluations, HPLC of Formula: 124-76-5, the main research area is Callosobruchus maculatus Deverra tortuosa essential oil nanoemulsion phenylpropanoid ecotoxicol; Biosafety; Deverra tortuosa; Ecofriendly pesticides; Essential oil; Nanoemulsion; Phenylpropanoids.

The essential oil (EO) was hydrodistd. from of Deverra tortuosa aerial parts. Fifty-six components amounting 99.3% were identified in EO through using gas chromatog.-fame ionization detection (GC-FID) and (GC-MS). Phenylpropanoids, dillapiole (41.6%), elemicin (7.3%) and myristicin (5.1%), and the monoterpene, sabinene (4.2%) were identified as the major terpenes. An oil-in-water nanoemulsion (particle size 70.3 nm) was developed from EO adopting a low-energy method. The EO products showed insecticidal and biochem. effects against the cowpea weevil Callosobruchus maculatus. Based on a 48-h exposure period, the oil nanoemulsion exhibited a superior contact bioactivity (LC50=10.3μg/cm2), followed by EO (LC50=23.1μg/cm2), dillapiole (LC50=27.8μg/cm2), and myristicin (LC50=37.1μg/cm2). Upon fumigation, nanoemulsion and EO were superior as fumigants (LC50 after 48 h were 6.9 and 14.3μl/l, resp.). Test materials showed a residual bioactivity against C. maculatus, where EO, dillapiole, and myristicin showed the strongest grain protecting activity. EO products significantly inhibited acetylcholinesterase (AChE) activity of C. maculatus adults. Test products were safe toward the non-target earthworms and did not alter the viability of cowpea seeds. There are evidences for the potential of using EO of D. tortuosa and its nanoemulsion and phenylpropanoids as natural grain protectants against C. maculatus.

Environmental Science and Pollution Research published new progress about Bioavailability. 124-76-5 belongs to class alcohols-buliding-blocks, name is rel-(1R,2R,4R)-1,7,7-Trimethylbicyclo[2.2.1]heptan-2-ol, and the molecular formula is C10H18O, HPLC of Formula: 124-76-5.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Franchin, Taisa Busaranho published the artcileAssessment of the Physicochemical Properties and Stability for Pharmacokinetic Prediction of Pyrazinoic Acid Derivatives, Recommanded Product: n-Octanol, the main research area is pharmacokinetics pyrazinoic acid stability physicochem property; Pyrazinoic acid; chemical stability; metabolism; permeability; pharmacokinetics; plasma stability.

Background: Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis, which still has high prevalence worldwide. In addition, cases of drug resistance are frequently observed In the search for new anti-TB drugs, compounds with antimycobacterial activity have been developed, such as derivatives of pyrazinoic acid, which is the main pyrazinamide metabolite. In a previous study, the compounds were evaluated and showed moderate antimycobacterial activity and no important cytotoxic profile; however, information about their pharmacokinetic profile is lacking. Objective: The aim of this work was to perform physicochem., permeability, and metabolic properties of four pyrazinoic acid esters. Method: The compounds were analyzed for their chem. stability, n-octanol:water partition coefficient (logP) and apparent permeability (Papp) in monolayer of Caco-2 cells. The stability of the compounds in rat and human microsomes and in rat plasma was also evaluated. Results: The compounds I, II and IV were found to be hydrophilic, while compound III was the most lipophilic (logP 1.59) compound The apparent permeability measured suggests good intestinal absorption of the compounds Addnl., the compounds showed metabolic stability under action of human and rat microsomal enzymes and stability in rat plasma for at least 6 h. Conclusion: The results bring favorable perspectives for the future development of the evaluated compounds and other pyrazinoic acid derivatives

Current Drug Metabolism published new progress about Bioavailability. 111-87-5 belongs to class alcohols-buliding-blocks, name is n-Octanol, and the molecular formula is C8H18O, Recommanded Product: n-Octanol.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Lategahn, Jonas published the artcileInhibition of osimertinib-resistant epidermal growth factor receptor EGFR-T790M/C797S, Name: 3-(Methylthio)propan-1-ol, the main research area is nonsmall cell lung cancer osimertinib EGFR drug resistance.

Precision medicine has revolutionized the treatment of patients in EGFR driven non-small cell lung cancer (NSCLC). Targeted drugs show high response rates in genetically defined subsets of cancer patients and markedly increase their progression-free survival as compared to conventional chemotherapy. However, recurrent acquired drug resistance limits the success of targeted drugs in long-term treatment and requires the constant development of novel efficient inhibitors of drug resistant cancer subtypes. Herein, we present covalent inhibitors of the drug resistant gatekeeper mutant EGFR-L858R/T790M based on the pyrrolopyrimidine scaffold. Biochem. and cellular characterization, as well as kinase selectivity profiling and western blot anal., substantiate our approach. Moreover, the developed compounds possess high activity against multi drug resistant EGFR-L858R/T790M/C797S in biochem. assays due to their highly reversible binding character, that was revealed by characterization of the binding kinetics. In addition, we present the first x-ray crystal structures of covalent inhibitors in complex with C797S-mutated EGFR which provide detailed insight into their binding mode.

Chemical Science published new progress about Bioavailability. 505-10-2 belongs to class alcohols-buliding-blocks, name is 3-(Methylthio)propan-1-ol, and the molecular formula is C4H10OS, Name: 3-(Methylthio)propan-1-ol.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts