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Molecules (Basel, Switzerland) May 2024The 1092 bp F3H gene from Roxb., which was named TbF3H, was cloned and it encodes 363 amino acids. Bioinformatic and phylogenetic tree analyses revealed the high...
The 1092 bp F3H gene from Roxb., which was named TbF3H, was cloned and it encodes 363 amino acids. Bioinformatic and phylogenetic tree analyses revealed the high homology of TbF3H with flavanone 3-hydroxylase from other plants. A functional analysis showed that TbF3H of Roxb. encoded a functional flavanone 3-hydroxylase; it catalyzed the formation of dihydrokaempferol (DHK) from naringenin in . The promoter strengths were compared by fluorescence microscopy and flow cytometry detection of the fluorescence intensity of the reporter genes initiated by each constitutive promoter (FITC), and DHK production reached 216.7 mg/L by the promoter adjustment strategy and the optimization of fermentation conditions. The results presented in this study will contribute to elucidating DHK biosynthesis in Roxb.
Topics: Saccharomyces cerevisiae; Flavanones; Phylogeny; Promoter Regions, Genetic; Cloning, Molecular; Flavonoids; Plant Proteins; Fermentation
PubMed: 38792058
DOI: 10.3390/molecules29102196 -
Marine Drugs May 2024Osteoarthritis (OA) is a debilitating joint disorder characterized by cartilage degradation and chronic inflammation, accompanied by high oxidative stress. In this...
Osteoarthritis (OA) is a debilitating joint disorder characterized by cartilage degradation and chronic inflammation, accompanied by high oxidative stress. In this study, we utilized the monosodium iodoacetate (MIA)-induced OA model to investigate the efficacy of oligo-fucoidan-based formula (FF) intervention in mitigating OA progression. Through its capacity to alleviate joint bearing function and inflammation, improvements in cartilage integrity following oligo-fucoidan-based formula intervention were observed, highlighting its protective effects against cartilage degeneration and structural damage. Furthermore, the oligo-fucoidan-based formula modulated the p38 signaling pathway, along with downregulating cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, contributing to its beneficial effects. Our study provides valuable insights into targeted interventions for OA management and calls for further clinical investigations to validate these preclinical findings and to explore the translational potential of an oligo-fucoidan-based formula in human OA patients.
Topics: Nitric Oxide Synthase Type II; Osteoarthritis; Animals; Cyclooxygenase 2; Polysaccharides; Male; Mice; Disease Models, Animal; Iodoacetic Acid; Oxidative Stress; Humans; Cartilage, Articular; Iodoacetates
PubMed: 38786602
DOI: 10.3390/md22050211 -
Marine Drugs May 2024The applications of fucoidan in the food industry were limited due to its high molecular weight and low solubility. Moderate degradation was required to depolymerize...
The applications of fucoidan in the food industry were limited due to its high molecular weight and low solubility. Moderate degradation was required to depolymerize fucoidan. A few studies have reported that fucoidan has potential antibacterial activity, but its antibacterial mechanism needs further investigation. In this study, the degraded fucoidans were obtained after ultraviolet/hydrogen peroxide treatment (UV/HO) at different times. Their physicochemical properties and antibacterial activities against and were investigated. The results showed that the average molecular weights of degraded fucoidans were significantly decreased (up to 22.04 times). They were mainly composed of fucose, galactose, and some glucuronic acid. Fucoidan degraded for 90 min (DFuc-90) showed the strongest antibacterial activities against and , with inhibition zones of 27.70 + 0.84 mm and 9.25 + 0.61 mm, respectively. The minimum inhibitory concentrations (MIC) were 8 mg/mL and 4 mg/mL, respectively. DFuc-90 could inhibit the bacteria by damaging the cell wall, accumulating intracellular reactive oxygen species, reducing adenosine triphosphate synthesis, and inhibiting bacterial metabolic activity. Therefore, UV/HO treatment could effectively degrade fucoidan and enhance its antibacterial activity.
Topics: Polysaccharides; Hydrogen Peroxide; Anti-Bacterial Agents; Ultraviolet Rays; Escherichia coli; Staphylococcus aureus; Microbial Sensitivity Tests; Molecular Weight; Reactive Oxygen Species
PubMed: 38786600
DOI: 10.3390/md22050209 -
Biomedicine & Pharmacotherapy =... Jun 2024Thrombocytopenia, a common adverse effect of linezolid, often occurs in patients lacking typical risk factors. In this study, we investigated the key risk factors for...
Thrombocytopenia, a common adverse effect of linezolid, often occurs in patients lacking typical risk factors. In this study, we investigated the key risk factors for linezolid-induced thrombocytopenia using two real-world clinical databases and explored its underlying mechanism through in vitro and in vivo experiments. In a retrospective analysis of 150 linezolid-treated patients, multivariate analysis identified coadministration of lansoprazole, a proton pump inhibitor, as a significant independent risk factor for thrombocytopenia (odds ratio: 2.33, p = 0.034). Additionally, analysis of the Food and Drug Administration Adverse Event Reporting System database revealed a reporting odds ratio of thrombocytopenia for lansoprazole of 1.64 (95% CI: 1.25-2.16). In vitro studies showed that the uptake of PNU-142586, a major linezolid metabolite, was significantly higher in human organic anion transporter 3-expressing HEK293 (HEK-hOAT3) cells compared to HEK-pBK cells. The apparent IC value of lansoprazole against hOAT3-mediated transport of PNU-142586 was 0.59 ± 0.38 µM. In a pharmacokinetic study using rats, coadministration of linezolid with lansoprazole intravenously resulted in approximately a 1.7-fold increase in the area under the plasma concentration-time curve of PNU-142586, but not linezolid and PNU-142300. Moreover, PNU-142586, but not linezolid, exhibited concentration-dependent cytotoxicity in a human megakaryocytic cell line. These findings suggest that linezolid-induced thrombocytopenia should be due to delayed elimination of PNU-142586. Furthermore, delayed elimination of PNU-142586 due to renal failure and hOAT3-mediated transport inhibition by lansoprazole should exacerbate linezolid-induced thrombocytopenia.
Topics: Linezolid; Humans; Thrombocytopenia; HEK293 Cells; Animals; Male; Female; Middle Aged; Retrospective Studies; Aged; Rats; Proton Pump Inhibitors; Lansoprazole; Biological Transport; Rats, Sprague-Dawley; Risk Factors; Adult; Organic Anion Transporters, Sodium-Independent
PubMed: 38781867
DOI: 10.1016/j.biopha.2024.116801 -
PloS One 2024Pigmented rice, especially black rice, is gaining popularity as it is rich in antioxidants such as anthocyanins and γ-oryzanol. At present, knowledge about temporal...
Pigmented rice, especially black rice, is gaining popularity as it is rich in antioxidants such as anthocyanins and γ-oryzanol. At present, knowledge about temporal control of biosynthesis and accumulation of antioxidants during grain development is limited. To address this, the accumulation patterns of anthocyanins and γ-oryzanol were assessed in two distinct black rice genotypes over the course of grain development, and the expression of known regulatory genes for anthocyanin biosynthesis was examined. The results indicated that total γ-oryzanol content increased continuously throughout grain development, while total anthocyanins peaked at dough stage (15 to 21 days after flowering) followed by a decline until grain maturity in both genotypes. However, the rate of decrease in anthocyanin content differed between genotypes, and a more prominent decline in cyanidin 3-O-glucoside (C3G) relative to peonidin 3-O-glucoside (P3G) was observed for both. Anthocyanin content was closely linked with the expression of key regulatory genes in the MBW (MYB-bHLH-WD40) complex. This improved knowledge of the genotype-specific biosynthesis (anthocyanins only) and accumulation patterns of anthocyanins and γ-oryzanol can inform subsequent research efforts to increase concentrations of these key antioxidants in black rice grains.
Topics: Anthocyanins; Oryza; Phenylpropionates; Gene Expression Regulation, Plant; Genotype; Glucosides; Edible Grain; Antioxidants; Plant Proteins
PubMed: 38776277
DOI: 10.1371/journal.pone.0302745 -
Veterinary Journal (London, England :... Jun 2024Abomasal ulcers are a significant concern in intensive animal farming due to their impact on animal health and productivity. While proton pump inhibitors (PPIs) such as... (Comparative Study)
Comparative Study
Abomasal ulcers are a significant concern in intensive animal farming due to their impact on animal health and productivity. While proton pump inhibitors (PPIs) such as pantoprazole (PTZ) show promise in treating these ulcers, data on PTZ's pharmacokinetics (PK) in adult goats and sheep are limited. This study aims to fill this gap by investigating and comparing PTZ's PK in these species following single intravenous (IV) and subcutaneous (SC) administrations. Five healthy male goats and sheep were included in the study. PTZ concentrations in plasma samples were determined using a validated analytical method. Non-compartmental analysis was conducted, and statistical comparisons were made between IV and SC administrations and between species. Sheep and goats showed similar systemic exposure levels regardless of the administration route. However, sheep had a shorter t1/2 due to a higher V compared to goats. Cl values were comparable in both species, with low extraction ratio values. There were no significant differences in C and T between the two species with regards to SC administration, and complete bioavailability was observed. The MAT exceeded the t1/2 in both species, indicating a potential flip-flop phenomenon. Considering the AUC as a predictor for drug efficacy, and observing no significant differences in systemic exposure between sheep and goats for any route of administration, dosage adjustment between the two species may not be necessary. In field settings, SC administration proves more practical, providing not only complete bioavailability but also a longer half-life compared to IV. Further studies are warranted to explore the PK/PD of PTZ in small ruminants with abomasal ulcers, to fully comprehend its therapeutic efficacy in such scenarios.
Topics: Animals; Goats; Male; Sheep; Pantoprazole; Injections, Subcutaneous; Injections, Intravenous; Proton Pump Inhibitors; Area Under Curve; Biological Availability; Half-Life
PubMed: 38761957
DOI: 10.1016/j.tvjl.2024.106138 -
International Journal of Colorectal... May 2024A high number of topical products are available for the treatment of hemorrhoidal symptoms. Sucralfate-based topical products constitute a new treatment alternative that... (Observational Study)
Observational Study
BACKGROUND AND AIMS
A high number of topical products are available for the treatment of hemorrhoidal symptoms. Sucralfate-based topical products constitute a new treatment alternative that act as a mechanical barrier to facilitate healing. The aim of this prospective, observational study was to determine patient- and physician-assessed effectiveness and tolerability of rectal ointment and suppositories containing sucralfate for the treatment of hemorrhoidal symptoms in routine clinical practice.
METHODS
Adult patients with diagnosed, mild-to-moderate, symptomatic non-bleeding hemorrhoids treated with rectal ointment or suppositories containing sucralfate were enrolled. Patients were administered treatment twice per day for at least 1 week until symptom resolution and/or for a maximum of 4 weeks. The primary endpoint was patient-assessed effectiveness on a modified Symptom Severity Score (mSSS, range 0 to 14). Physician-assessed effectiveness (9 symptoms, 0 to 5 Likert scale), hemorrhoid grade, and patient satisfaction were also determined.
RESULTS
Five investigators enrolled 60 patients; mean age was 48.4 ± 16.6 years and 72.4% were female. Pain or pressure sensitivity was reported as the most severe symptom by patients, and pressure sensitivity, discharge, soiling, and prolapse by physicians. Mean patient-assessed mSSS at baseline was 6.6 ± 1.9 and was significantly improved overall and in the ointment and suppository groups individually by -4.6 ± 2.0, -4.4 ± 1.8, and -4.8 ± 2.2, respectively (p < 0.0001). Investigator-assessed mean baseline symptom score was 18.1 ± 3.9 and improved by -7.1 ± 4.5, -6.9 ± 5.4, and -7.3 ± 3.5, respectively (p < 0.0001). Investigator-assessed symptoms of pressure sensitivity, swelling, and discharge were improved to the greatest extent. Hemorrhoid grade was improved in 38% of patients at the end of treatment. Compliance with treatment was 97.4% and patient satisfaction with application and onset of action was high (81.3% and 76.2%, respectively). Both the ointment and suppository were well tolerated.
CONCLUSIONS
The effectiveness of topical ointment or suppository containing sucralfate on patient- and investigator-assessed hemorrhoidal symptoms in real-life clinical practice was demonstrated. Patient satisfaction was high and treatments were well tolerated. Larger controlled trials are warranted to confirm the results.
Topics: Humans; Sucralfate; Hemorrhoids; Female; Suppositories; Male; Middle Aged; Ointments; Prospective Studies; Treatment Outcome; Patient Satisfaction; Adult; Aged; Administration, Rectal
PubMed: 38750150
DOI: 10.1007/s00384-024-04642-7 -
Chemical & Pharmaceutical Bulletin 2024The solid-state properties of drug candidates play a crucial role in their selection. Quality control of active pharmaceutical ingredients (APIs) based on their...
The solid-state properties of drug candidates play a crucial role in their selection. Quality control of active pharmaceutical ingredients (APIs) based on their structural information involves ensuring a consistent crystal form and controlling water and residual solvent contents. However, traditional crystallographic techniques have limitations and require high-quality single crystals for structural analysis. Microcrystal electron diffraction (microED) overcomes these challenges by analyzing difficult-to-crystallize or small-quantity samples, making it valuable for efficient drug development. In this study, microED analysis was able to rapidly determine the configuration of two crystal forms (Forms 1, 2) of the API ranitidine hydrochloride. The structures obtained with microED are consistent with previous structures determined by X-ray diffraction, indicating microED is a useful tool for rapidly analyzing molecular structures in drug development and materials science research.
Topics: Ranitidine; Crystallization; Molecular Structure; Electrons
PubMed: 38749738
DOI: 10.1248/cpb.c23-00745 -
Emerging Microbes & Infections Dec 2024The study investigates the potential of lansoprazole, a proton pump inhibitor, to interfere with fungal respiration and enhance the antifungal activity of amphotericin B...
The study investigates the potential of lansoprazole, a proton pump inhibitor, to interfere with fungal respiration and enhance the antifungal activity of amphotericin B against multidrug-resistant Candida auris. The authors administered lansoprazole at concentrations significantly higher than typical therapeutic doses, which demonstrated promising results but also raised concerns about potential toxicity. We suggest incorporating a control group, monitoring toxicity indicators, performing pathological examinations, and conducting cellular assays to improve the study's rigor and reliability. We also highlight the need for further research into the mechanisms of lansoprazole's antifungal activity, its long-term effects on amphotericin B resistance, and potential drug-drug interactions with amphotericin B. Addressing these concerns is crucial for the clinical translation of lansoprazole as an adjuvant to amphotericin B.
Topics: Lansoprazole; Amphotericin B; Antifungal Agents; Drug Resistance, Multiple, Fungal; Drug Synergism; Microbial Sensitivity Tests; Humans; Candida auris; Candidiasis; Proton Pump Inhibitors
PubMed: 38742537
DOI: 10.1080/22221751.2024.2356144 -
Experimental Gerontology Jul 2024Sorghum is a promising treatment for Alzheimer's disease (AD), due to its rich antioxidant and anti-inflammatory qualities. Fermentation may also affect nutritional...
Sorghum is a promising treatment for Alzheimer's disease (AD), due to its rich antioxidant and anti-inflammatory qualities. Fermentation may also affect nutritional values. Therefore, the purpose of this study was to discover the phenolic and flavonoid chemicals found in both fermented and non-fermented red sorghum, as well as their potential therapeutic uses for AD. L. fermentum, and L. reuteri, and/or L. plantarum and L. casei were used to ferment samples of sorghum. The rats were grouped into five groups, healthy animals, and rats with Alzheimer's receiving 200 mg/kg of saline, non-fermented sorghum, and fermented sorghum fermented with L. fermentum and L. reuteri, as well as L. plantarum and L. casei. Various assessments were conducted, including evaluations of behavioral responses, antioxidant responses, inflammatory responses, acetylcholine levels and acetylcholine esterase, and bacterial populations in stool. P-hydroxybenzoic acid, eriodictyo naringenin, and apigenin were significantly higher in fermented samples, while glycerols were higher in non-fermented samples. The induction of Alzheimer's led to decrease step-through latency, time in target zone, FRAP, acetylcholine levels, Bifidobacterium population and lactobacillus population, while increased escape latency, platform location latency, MDA levels, IL-6, TNF-α, acetylcholine esterase, and coliform population (P = 0.001). The administration of both non-fermented sorghum and fermented sorghum demonstrated the potential to reverse the effects of AD, with a notably higher efficacy observed in the fermented samples compared to the non-fermented ones. In conclusion, fermentation exerted significant effects on the bioactive compounds the administration of fermented sorghum resulted in improved behavioral responses, characterized by a reduction in oxidation, inflammation and microbial population.
Topics: Sorghum; Alzheimer Disease; Fermentation; Animals; Male; Antioxidants; Rats; Rats, Wistar; Flavanones; Gastrointestinal Microbiome; Disease Models, Animal; Flavonoids; Apigenin; Phenols; Acetylcholine; Acetylcholinesterase; Anti-Inflammatory Agents; Lactobacillus; Plant Extracts; Feces
PubMed: 38740315
DOI: 10.1016/j.exger.2024.112459