Результаты поиска

Структура, основанная на силико-диагностике естественных витаминов D для целенаправленного и более безопасного лечения резистентного множественного склероза.

Множественный склероз (MS) — хроническое аутоиммунное расстройство, которое вызывает прогрессивную неврологическую недостаточность в результате демиэлизации центральной нервной системы. Недостаток витамина D связан с повышенным риском и активностью MS, при этом были продемонстрированы адекватные уровни для модуляции иммунной реакции. Вместе с тем многие пациенты с синдромом MS демонстрируют устойчивость к высокодозированной терапии витамина D, зачастую из-за неправильной активации витамина D-рецептора (VDR), что ограничивает его терапевтическую эффективность и повышает риск побочных эффектов.

Совпадение в аннотации оригинала
Multiple Sclerosis (MS) is a chronic autoimmune disorder that causes progressive neurological disability through demyelination of the centra … bition constants (Ki) of 1.13 nM and 1.33 nM, respectively, showed high binding affinity, favorable gastrointestinal absorption, and the ability to cross the blood-brain barrier. These compounds were further analyzed via 200 ns molecular dynamics (MD) simulations, which demonstrated strong and stable interactions with key VDR residues, such as ALA135 and HIS137. Both analogs …

Toward New Therapeutics for Visceral Leishmaniasis: Efficacy and Mechanism of Action of Amides Inspired by Gibbilimbol B.

The problems with current strategies to control canine visceral Leishmaniasis (CVL), which include the euthanasia of infected animals, and a … pectively. In silico drug-likeness studies predicted that these compounds would show high levels of gastrointestinal absorption, would be able to penetrate the blood-brain barrier, would show moderate solubility, and would not show unwanted molecular interactions. Due to their promising pharmacological profiles, compounds 9 and 10 were selected for mechanism of action studie …

Population pharmacokinetics and limited sampling strategy for therapeutic drug monitoring of mycophenolate mofetil in Japanese patients with lupus nephritis.

BACKGROUND: Mycophenolate mofetil (MMF), a prodrug of the immunosuppressive agent mycophenolic acid (MPA), is difficult to administer because of the pharmacokinetic complexity of MPA. Although dosage adjustment according to the 12-h area under the concentration-time curve (AUC0-12) is thought to be desirable, multiple blood samplings for AUC calculation may pose a clinical challenge. A limited sampling strategy (LSS) would provide a solution; however, little is known about MPA pharmacokinetics in lupus nephritis patients, especially in those with Asian backgrounds, or few, if any, LSSs are rep

Enumeration of olive derived lignan, pinoresinol for activity against recent Omicron variant spike protein for structure-based drug design, DFT, molecular dynamics simulations, and MMGBSA studies.

The coronavirus disease 2019 (COVID-19) was first found in Wuhan, China, in December 2019. Because the virus spreads quickly, it quickly bec … ase of drug molecules obtained from the OliveNet™ database. Compounds that did not exhibit adequate gastrointestinal absorption and failed the Lipinski test are not considered for further research. The filtered compounds were coupled with our primary target, SARS-CoV-2 Omicron spike protein. We focused on SARS-CoV-2 Omicron spike protein and filtering potent olive compounds. …

In Vivo and In Silico Analgesic Activity of Ficus populifolia Extract Containing 2-O-β-D-(3',4',6'-Tri-acetyl)-glucopyranosyl-3-methyl Pentanoic Acid.

Natural product-based structural templates have immensely shaped small molecule drug discovery, and new biogenic natural products have randomly provided the leads and molecular targets in anti-analgesic activity spheres. Pain relief achieved through opiates and non-steroidal anti-inflammatory drugs (NSAIDs) has been under constant scrutiny owing to their tolerance, dependency, and other organs toxicities and tissue damage, including harm to the gastrointestinal tract (GIT) and renal tissues. A new, 3',4',6'-triacetylated-glucoside, 2-O-β-D-(3',4',6'-tri-acetyl)-glucopyranosyl-3-methyl pentanoi

Effects of whole maize high-grain diet feeding on colonic fermentation and bacterial community in weaned lambs.

High-grain diet is commonly used in intensive production to boost yield in short term, which may cause adverse effects such as rumen and colonic acidosis in ruminants. Maize is one of the key components of high-grain diet, and different processing methods of maize affect the digestive absorption and gastrointestinal development of ruminants. To investigate the effects of maize form in high-grain diets on colonic fermentation and bacterial community of weaned lambs, twenty-two 2.5-month-old healthy Hu lambs were fed separately a maize meal low-grain diet (19.2% grain; CON), a maize meal high-gr

The protective effects of curcumin on metabolic syndrome and its components: In-silico analysis for genes, transcription factors, and microRNAs involved.

BACKGROUND: We aimed to identify the molecular mechanisms behind curcumin's therapeutic benefits for metabolic syndrome (MetS) and its compo … cs are closely connected with its therapeutic advantages in MetS and its components due to its high gastrointestinal absorption, drug-likeness, water solubility, and lipophilic nature. Curcumin is a CYP1A9 and CYP3A4 inhibitor. Although curcumin has a low bioavailability, it can be synthesized and administered to increase its pharmacokinetic features. CONCLUSIONS: Curcumin …

Use of Teduglutide in Children With Intestinal Failure: A Systematic Review.

BACKGROUND AND OBJECTIVES: Short-bowel syndrome (SBS) results from the loss of a significant portion of the small intestine leading to a state of malabsorption. After an intestinal loss, there is a process of adaptation involving the Glucagon-Like Peptide-2 (GLP-2), an enteroendocrine peptide also involved in nutrient absorption. Teduglutide is a recombinant analog of GLP-2 approved in 2016 to treat selected SBS pediatric patients who are dependent on parenteral support. The present systematic review aims to evaluate the efficacy of Teduglutide in pediatric patients with SBS in reducing the ne

miR-29a, b, and c regulate SLC5A8 expression in intestinal epithelial cells.

Short-chain fatty acids (SCFAs) produced by bacterial fermentation of dietary fiber exert myriad of beneficial effects including the amelioration of inflammation. SCFAs exist as anions at luminal pH; their entry into the cells depends on the expression and function of monocarboxylate transporters. In this regard, sodium-coupled monocarboxylate transporter-1 (SMCT-1) is one of the major proteins involved in the absorption of SCFA in the mammalian colon. However, very little is known about the mechanisms of regulation of SMCT-1 expression in health and disease. MicroRNAs (miRs) are known to play

Canola meal or soybean meal as protein source and the effect of microencapsulated sodium butyrate supplementation in calf starter mixture. II. Development of the gastrointestinal tract.

The aim of this study was to assess the effect of protein source, either soybean meal (SM) or canola meal (CM), and microencapsulated sodium butyrate (MSB) supplementation in a pelleted starter mixture on the development of the gastrointestinal tract (GIT) in dairy calves. Twenty-eight bull calves (8.7 ± 0.8 d of age and 43.0 ± 4.4 kg; mean ± SD) were assigned to 1 of 4 treatments in a 2 × 2 factorial arrangement: CM as a main source of protein without or with MSB or SM without or with MSB. Calves were fed starters ad libitum and exposed to a gradual weaning program, with weaning taking place

Quantification of P-Glycoprotein in the Gastrointestinal Tract of Humans and Rodents: Methodology, Gut Region, Sex, and Species Matter.

Intestinal efflux transporters affect the gastrointestinal processing of many drugs but further data on their intestinal expression levels are required. Relative mRNA expression and relative and absolute protein expression data of transporters are commonly measured by real-time polymerase chain reaction (RT-PCR), Western blot and mass spectrometry-based targeted proteomics techniques. All of these methods, however, have their own strengths and limitations, and therefore, validation for optimized quantification methods is needed. As such, the identification of the most appropriate technique is

Comparison of invasive fungal diseases between patients with acute myeloid leukemia receiving posaconazole prophylaxis and those not receiving prophylaxis: A single-center, observational, case-control study in South Korea.

Posaconazole prophylaxis is effective in decreasing the incidence of invasive fungal diseases (IFDs) in patients with acute myeloid leukemia (AML). However, the use of antifungal prophylaxis varies in real-life practice, and only a small number of studies have compared the incidence of IFDs between those receiving posaconazole prophylaxis and those without prophylaxis. We compared the clinical characteristics and outcomes of IFDs between patients with AML who received posaconazole prophylaxis and those without antifungal prophylaxis.We reviewed the medical records of adult AML patients who und

Age-associated changes in caecal microbiome and their apparent correlations with growth performances of layer pullets.

The microbiome in gastrointestinal tracts play an important role in regulating nutrient utilization and absorption, gut immune function, and host growth or development. This study was conducted to investigate the composition and dynamic distribution of caecal microbiota in pullets during the first 16 weeks. Growth performance, immune organs index, and intestinal morphology of pullets were analyzed at 3, 6, 12 and 16 weeks of age. The caecal contents were collected for microbiota analysis by 16S rRNA gene sequencing method. With advancing ages in pullets, the gradually increased average daily f

A Network Pharmacology-Based Investigation to the Pharmacodynamic Material Basis and Mechanisms of the Anti-Inflammatory and Anti-Viral Effect of Isatis indigotica.

PURPOSE: Isatis indigotica (Ii) is a cruciferous herb that is widely distributed in China, and its roots and leaves have been used in two re … l profiling of R and F Isatidis. The active ingredients were screened out through the prediction of gastrointestinal absorption and druglikeness analysis using SwissADME. A herb-ingredient-target network was constructed through target prediction of the herbal active ingredients and anti-inflammation or anti-viral properties, followed by protein-protein interaction analysis. …

Urinary Lithogenic Risk Profile in ADPKD Patients Treated with Tolvaptan.

BACKGROUND AND OBJECTIVES: Nephrolithiasis is a common health problem in autosomal dominant polycystic kidney disease (ADPKD) and significantly contributes to patient morbidity. Recently, Tolvaptan has been introduced for the treatment of ADPKD, but whether it is associated with alterations of the urinary lithogenic risk profile remains unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted an analysis of participants enrolled in the Bern ADPKD registry, a prospective observational cohort study. Twenty-four-hour urine analyses were performed at baseline and then at yearly follow

[Pleural mesothelioma mortality in Italy: time series reconstruction (1970-2009) and comparison with incidence (2003-2008)].

BACKGROUND: The American Society of Hematology reported that according to the National Heart, Lung, and Blood Institute (NHLBI) anemia is the most common blood disorder, which affects more than 3 million Americans, while the Global Burden of Disease 2016 (GBD 2016) reported that iron deficiency anemia (IDA) is the leading cause of anemia, which affects 1.93 billion people worldwide. Anemia is intricately linked to chronic inflammation, chronic kidney disease, gastrointestinal and gynecological malignancies, and autoimmune disorders. Hemorrhagic anemia results in substantial loss of blood, whic

Development and validation of a comprehensive semi-quantitative food frequency questionnaire that includes FODMAP intake and glycemic index.

BACKGROUND: Fermentable, short chain carbohydrates (FODMAPs) have been identified as triggers for functional gastrointestinal symptoms. In addition, excess FODMAP consumption has been implicated in the onset of Crohn's disease, and animal studies suggest that a low glycemic index diet can impair absorption of fructose, a major dietary FODMAP. Such hypotheses cannot be tested without the ability to quantify FODMAP ingestion with a validated dietary assessment tool. OBJECTIVE: To assess the validity and reproducibility of a 297-item comprehensive, semi-quantitative food frequency questionnaire

Gastrointestinal dysfunction in mice with a targeted mutation in the gene encoding vasoactive intestinal polypeptide: a model for the study of intestinal ileus and Hirschsprung's disease.

In 1970, Drs. Said and Mutt isolated a novel peptide from porcine intestinal extracts with powerful vasoactive properties, and named it vasoactive intestinal peptide (VIP). Since then, the biological actions of VIP in the gut as well as its signal transduction pathways have been extensively studied. A variety of in vitro and in vivo studies have indicated that VIP, expressed in intrinsic non-adrenergic non-cholinergic (NANC) neurons, is a potent regulator of gastrointestinal (GI) motility, water absorption and ion flux, mucus secretion and immune homeostasis. These VIP actions are believed to

The safety profile of moxifloxacin and other fluoroquinolones in special patient populations.

BACKGROUND: Fluoroquinolones, including ciprofloxacin, levofloxacin, gemifloxacin, and moxifloxacin, represent a major advance in the development of antimicrobial agents. They offer significant activity against Gram-negative pathogens, while more advanced generation fluoroquinolones including levofloxacin, gemifloxacin, and moxifloxacin are significantly active against Gram-positive (e.g., Streptococcus pneumoniae for some members of the class), typical, atypical, and anaerobic pathogens. Fluoroquinolones have a pharmacokinetic/pharmacodynamic profile that exhibits concentration-dependent kill

Omega-3 fatty acids in immune-enhancing enteral diets selectively increase blood flow to the ileum by a bile acid dependent mechanism.

BACKGROUND: The immune-enhancing diet (IED) (Impact, Novartis Corp, Minneapolis, Minn) initiates a delayed and sustained increase in blood flow to the ileum and gut-associated lymphoid tissue. The immune-enhancing benefits of Impact (Novartis Corp) are attributed to the addition of L-arginine, fish oil (FO), and RNA fragments to a standard enteral diet. The sustained increase in blood flow to the gut-associated lymphoid tissue during IED exposure might account for these immune effects. We hypothesized that the increase in ileal blood flow with IED might be a result of ileal omega-3 fatty acid