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Journal of Ethnopharmacology Oct 2024Zingiberis rhizoma recens-/wine-/euodiae fructus-processed Coptidis Rhizoma (CR, zCR/wCR/eCR) are the commonly used processed products of CR in clinic. After being...
Untargeted serum and gastric metabolomics and network pharmacology analysis reveal the superior efficacy of zingiberis rhizoma recens-/euodiae fructus-processed Coptidis Rhizoma on gastric ulcer rats.
ETHNOPHARMACOLOGICAL RELEVANCE
Zingiberis rhizoma recens-/wine-/euodiae fructus-processed Coptidis Rhizoma (CR, zCR/wCR/eCR) are the commonly used processed products of CR in clinic. After being processed with different excipients, the efficacy of CR will change accordingly. I.e., wCR could resolve excessive heat of the upper energizer, zCR could eliminate gastric heat and harmonize the stomach, eCR could smooth the liver and harmonize the stomach. However, the underlying mechanisms were still unclear.
AIM OF THE STUDY
To further verify the differential efficacy of the three processed CR products and compare the mechanisms on gastric ulcer.
MATERIAL AND METHODS
First, a GU model, whose onset is closely related to the heat in stomach and the disharmony between liver and stomach, was established, and the therapeutic effects of zCR/wCR/eCR/CR were evaluated by pathologic observation and measurement of cytokine levels. Second, metabolomics analysis and network pharmacology were conducted to reveal the differential intervening mechanism of zCR/eCR on GU. Third, the predicted mechanisms from metabolomics analysis and network pharmacology were validated using western blotting, flow cytometry and immunofluorescence.
RESULTS
zCR/wCR/eCR/CR could alleviate the pathologic damage to varying degrees. In metabolomics research, fewer metabolic pathways were enriched in serum samples, and most of them were also present in the results of gastric tissue samples. The gastroprotective, anti-inflammatory, antioxidant, and anti-apoptotic effects of zCR/wCR/eCR/CR might be due to their interference on histidine, arachidonic acid, and glycerophospholipids metabolism. Quantitative results indicated that zCR/eCR had a better therapeutic effect than wCR/CR in treating GU. A comprehensive analysis of metabolomics and network pharmacology revealed that zCR and eCR exerted anti-GU effects via intervening in five core targets, including AKT, TNF, IL6, IL1B and PPARG. In the validation experiment, zCR/eCR could significantly reverse the abnormal expression of proteins related to apoptosis, inflammation, oxidative stress, gastric function, as well as the PI3K/AKT signaling pathways.
CONCLUSION
zCR and eCR could offer gastroprotective benefits by resisting inflammation and apoptosis, inhibiting gastric-acid secretion, as well as strengthening gastric mucosal defense and antioxidant capacity. Integrating network pharmacology and metabolomics analysis could reveal the acting mechanism of drugs and promote the development of medications to counteract GU.
Topics: Animals; Stomach Ulcer; Metabolomics; Network Pharmacology; Drugs, Chinese Herbal; Male; Rats, Sprague-Dawley; Rats; Evodia; Gastric Mucosa; Coptis chinensis; Disease Models, Animal; Anti-Ulcer Agents; Cytokines
PubMed: 38782310
DOI: 10.1016/j.jep.2024.118376 -
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 -
Obstetrics and Gynecology Jul 2024To compare 24-hour and 12-hour mifepristone-to-misoprostol intervals for second-trimester medication abortion. (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
OBJECTIVE
To compare 24-hour and 12-hour mifepristone-to-misoprostol intervals for second-trimester medication abortion.
METHODS
We conducted a prospective randomized controlled trial. Participants were allocated to receive mifepristone either 24 hours or 12 hours before misoprostol administration. The primary outcome was the time from the first misoprostol administration to abortion (induction time). Secondary outcomes included the time from mifepristone to abortion (total abortion time); fetal expulsion percentages at 12, 24, and 48 hours after the first misoprostol dose; side effects proportion; and pain and satisfaction scores. A sample size of 40 per group (N=80) was planned to compare the 24- and 12-hour regimens.
RESULTS
Eighty patients were enrolled between July 2020 and June 2023, with 40 patients per group. Baseline characteristics were comparable between groups. Median induction time was 9.5 hours (95% CI, 10.3-17.8 hours) and 12.5 hours (95% CI, 13.5-20.2 hours) in the 24- and 12-hour interval arms, respectively ( P =.028). Median total abortion time was 33.0 hours (95% CI, 34.2-41.9 hours) and 24.5 hours (95% CI, 25.7-32.4 hours) in the 24- and 12-hour interval groups, respectively ( P <.001). At 12 hours from misoprostol administration, 25 patients (62.5%) in the 24-hour arm and 18 patients (45.0%) in the 12-hour arm completed abortion ( P =.178). At 24 hours from misoprostol administration, 36 patients (90.0%) in the 24-hour arm and 30 patients (75.0%) in the 12-hour arm had complete abortion ( P =.139). The need for additional medication or surgical treatment for uterine evacuation, pain scores, side effects, and satisfaction levels were not different between groups.
CONCLUSION
A 24-hour mifepristone-to-misoprostol regimen for medication abortion in the second trimester provides a median 3-hour shorter induction time compared with the 12-hour interval. However, the median total abortion time was 8.5-hours longer in the 24-hour interval regimen. These findings can aid in shared decision making before medication abortion in the second trimester.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, NCT04160221.
Topics: Humans; Female; Misoprostol; Mifepristone; Pregnancy; Pregnancy Trimester, Second; Abortion, Induced; Adult; Drug Administration Schedule; Prospective Studies; Abortifacient Agents, Nonsteroidal; Young Adult; Time Factors; Abortifacient Agents, Steroidal
PubMed: 38781593
DOI: 10.1097/AOG.0000000000005535 -
International Journal of Pharmaceutics Jun 2024The smart oral administration Insulin device has the potential to improve glycemic management. It can reduce the risk of hypoglycemia associated with exogenous Insulin...
The smart oral administration Insulin device has the potential to improve glycemic management. It can reduce the risk of hypoglycemia associated with exogenous Insulin (INS) therapy while also avoiding many of the disadvantages associated with subcutaneous injections. Furthermore, diabetes mellitus (DM) is an endocrine illness characterized by inflammation, and it is critical to minimize the amount of inflammatory markers in diabetic patients while maintaining average blood glucose. In this study, a responsive nanosystem vitamin B12-Fucoidan-Concanavalin A (VB12-FU-ConA NPs) with anti-inflammatory action was developed for smart oral delivery of Insulin. Con A has high sensitivity and strong specificity as a glucose-responsive material. Fucoidan has anti-inflammatory, immunomodulatory, and hypoglycemic functions, and it can bind to Con A to form a reversible complex. Under high glucose conditions, free glucose competitively binds to Con A, which swells the nanocarrier and promotes Insulin release. Furthermore, in the low pH environment of the gastrointestinal tract, positively charged VB12 and anionic fucoidan bind tightly to protect the Insulin wrapped in the carrier, and VB12 can also bind to intestinal epithelial factors to improve transit rate, thereby promoting INS absorption. In vitro tests showed that the release of nanoparticles in hyperglycemic solutions was significantly higher than the drug release in normoglycemic conditions. Oral delivery of the nanosystems dramatically lowered blood glucose levels in type I diabetic mice (T1DM) during in vivo pharmacodynamics, minimizing the risk of hypoglycemia. Blood glucose levels reached a minimum of 8.1 ± 0.4 mmol/L after 8 h. Administering the nanosystem orally notably decreased the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in diabetic mice. The nano delivery system can be degraded and metabolized in the intestinal tract after being taken orally, demonstrating good biodegradability and biosafety. In conclusion, the present study showed that VB12-FU-ConA nanocarriers are expected to be a novel system for rationalizing blood glucose.
Topics: Animals; Polysaccharides; Blood Glucose; Administration, Oral; Insulin; Hypoglycemic Agents; Mice; Anti-Inflammatory Agents; Diabetes Mellitus, Experimental; Male; Vitamin B 12; Nanoparticles; Drug Liberation; Drug Carriers; Humans
PubMed: 38777304
DOI: 10.1016/j.ijpharm.2024.124250 -
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 -
Pharmacoepidemiology and Drug Safety Jun 2024Antisecretory drugs are commonly prescribed with clopidogrel-based dual antiplatelet therapy (DAPT) to prevent gastrointestinal bleeding in high-risk patients after...
BACKGROUND
Antisecretory drugs are commonly prescribed with clopidogrel-based dual antiplatelet therapy (DAPT) to prevent gastrointestinal bleeding in high-risk patients after percutaneous coronary intervention (PCI). However, omeprazole and esomeprazole (inhibiting proton pump inhibitors [PPIs]) may increase cardiovascular event rates on co-administration with clopidogrel. This study aimed to examine trends in the use of antisecretory agents in patients administered clopidogrel-based DAPT and the concomitant use of clopidogrel and inhibiting PPIs.
METHODS
We used National Inpatient Sample data compiled by the Health Insurance Review & Assessment Service from 2009 to 2020. Further, we identified patients who were prescribed clopidogrel-based DAPT after PCI and investigated the concomitant use of antisecretory agents with clopidogrel. To verify the annual trend of drug utilization, we used the Cochran-Armitage trend test.
RESULTS
From 2009 to 2020, the percentage of H2 receptor antagonist users decreased steadily (from 82.5% in 2009 to 25.3% in 2020); instead, the percentage of PPI users increased (from 23.7% in 2009 to 82.0% in 2020). The use of inhibiting PPI also increased (from 4.2% in 2009 to 30.7% in 2020). Potassium competitive acid blockers (P-CABs) were rarely used before 2019; however, in 2020, it accounted for 7.8% of the antisecretory users.
CONCLUSIONS
Our study demonstrates that the use of inhibiting PPIs increased steadily in patients administered clopidogrel-based DAPT therapy. This is a major concern since the concomitant use of inhibiting PPIs with clopidogrel could increase the risk of cardiovascular events.
Topics: Humans; Clopidogrel; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Proton Pump Inhibitors; Male; Female; Aged; Middle Aged; Gastrointestinal Hemorrhage; Dual Anti-Platelet Therapy; Esomeprazole; Omeprazole; Drug Interactions; Drug Therapy, Combination; Histamine H2 Antagonists
PubMed: 38773801
DOI: 10.1002/pds.5816 -
Issues in Law & Medicine 2024The U.S. FDA has permanently removed the in-person prescribing requirements that previously safeguarded the use of mifepristone/misoprostol medical abortions, allowing...
The U.S. FDA has permanently removed the in-person prescribing requirements that previously safeguarded the use of mifepristone/misoprostol medical abortions, allowing prescribing through telemedicine or on-line ordering and distribution through the mail and pharmacies, without standard pre-abortion testing. This will increase the risk of complications due to failure to adequately determine the gestational age or rule out ectopic pregnancy by ultrasound or physical exam, failure to perform labs to document whether RhoGAM is indicated, and failure to obtain appropriate informed consent to prevent unwanted abortions, among other concerns. The FDA justified this action by referencing flawed studies with significantly undercounted complications. The details of these study deficiencies are examined in this paper.
Topics: United States; United States Food and Drug Administration; Humans; Pregnancy; Abortion, Induced; Female; Misoprostol; Mifepristone
PubMed: 38771713
DOI: No ID Found -
The Analyst Jun 2024Real-time and non-invasive assessment of tissue health is crucial for maximizing the potential of microphysiological systems (MPS) for drug-induced nephrotoxicity...
Real-time and non-invasive assessment of tissue health is crucial for maximizing the potential of microphysiological systems (MPS) for drug-induced nephrotoxicity screening. Although impedance has been widely considered as a measure of the barrier function, it has not been incorporated to detect cell detachment in MPS with top and bottom microfluidic channels separated by a porous membrane. During cell delamination from the porous membrane, the resistance between both channels decreases, while capacitance increases, allowing the detection of such detachment. Previously reported concepts have solely attributed the decrease in the resistance to the distortion of the barrier function, ignoring the resistance and capacitance changes due to cell detachment. Here, we report a two-channel MPS with integrated indium tin oxide (ITO) electrodes capable of measuring impedance in real time. The trans-epithelial electrical resistance (TEER) and tissue reactance (capacitance) were extracted from the impedance profiles. We attributed the anomalous initial increase observed in TEER, upon cisplatin administration, to the distortion of tight junctions. Cell detachment was captured by sudden jumps in capacitance. TEER profiles illuminated the effects of cisplatin and cimetidine treatments in a dose-dependent and polarity-dependent manner. The correspondence between TEER and barrier function was validated for a continuous tissue using the capacitance profiles. These results demonstrate that capacitance can be used as a real-time and non-invasive indicator of confluence and will support the accuracy of the drug-induced cytotoxicity assessed by TEER profiles in the two-channel MPS for the barrier function of a cell monolayer.
Topics: Cisplatin; Kidney Tubules, Proximal; Electric Impedance; Animals; Tin Compounds; Kinetics; Cimetidine; Cell Adhesion; Electrodes; Epithelial Cells; Cell Line; Humans; Tight Junctions
PubMed: 38767610
DOI: 10.1039/d4an00267a -
Pakistan Journal of Pharmaceutical... Mar 2024To develop a new kind of famotidine-resin microcapsule for gastric adhesion sustained release by screening out suitable excipients and designing reasonable prescriptions...
To develop a new kind of famotidine-resin microcapsule for gastric adhesion sustained release by screening out suitable excipients and designing reasonable prescriptions to improve patient drug activities to achieve the expected therapeutic effect. The famotidine drug resin was prepared using the water bath method with carbomer 934 used as coating material. Microcapsules were prepared using the emulsified solvent coating method and appropriate excipients were used to prepare famotidine sustained release suspension. Pharmacokinetics of the developed microcapsules were studied in the gastrointestinal tract of rats. The self-made sustained-release suspension of famotidine hydrochloride effectively reduced the blood concentration and prolonged the action time. The relative bioavailability of the self-made suspension of the famotidine hydrochloride to the commercially available famotidine hydrochloride was 146.44%, with an average retention time of about 5h longer, which indicated that the new suspension had acceptable adhesion properties. The findings showed that the newly developed famotidine-resin microcapsule increased the bioavailability of the drug with a significant sustained-release property.
Topics: Famotidine; Delayed-Action Preparations; Animals; Biological Availability; Rats; Male; Excipients; Suspensions; Capsules; Drug Liberation; Acrylic Resins; Histamine H2 Antagonists; Adhesiveness; Drug Compounding; Acrylates
PubMed: 38767108
DOI: No ID Found -
Pakistan Journal of Pharmaceutical... Mar 2024A drug-resin liquid delayed-release suspension of pantoprazole sodium (PAZ-Na) was prepared to improve the effectiveness, convenience and safety of peptic ulcer...
A drug-resin liquid delayed-release suspension of pantoprazole sodium (PAZ-Na) was prepared to improve the effectiveness, convenience and safety of peptic ulcer treatment in children, the elderly and patients with dysphagia. Pantoprazole sodium drug-resin complexes (PAZ-Na-DRC) were prepared using the bath method. The fluidized bed coating method is used to coat it and then add excipients to make a dry suspension prepared before use. The parameters of the in vitro release experimental conditions were optimized and the drug release curve showed delayed release. Rats were given commercial PAZ-Na enteric-coated pellet capsules and the PAZ-Na delayed release suspension via intragastric administration. The results showed that the T of the PAZ-Na delayed release suspension was increased from 2h to 4h compared with the PAZ-Na enteric-coated pellet capsules. Similarly, the C was reduced from 6.162μg/mL to 3.244μg/mL with the concentration-time curve is very gentle compared with the commercial drug capsules. After oral administration, the relative bioavailability of PAZ-Na delayed release suspension (AUC of 19.578 μg•h•mL) compared with the commercial drug (AUC of 17.388 μg•h•mL) was 112.67%. The findings showed that the PAZ-Na delayed release suspension for oral administration was successfully formulated with highly improved pharmacokinetic indices.
Topics: Pantoprazole; Animals; Delayed-Action Preparations; Male; Suspensions; Rats; Drug Liberation; Biological Availability; Administration, Oral; Drug Compounding; Excipients; Rats, Sprague-Dawley
PubMed: 38767106
DOI: No ID Found