Evaluation of potential drug interactions of oral anticoagulants in outpatients based on pharmacy information databases

The interactions between hypoglycemic drugs and other drugs were retrieved based on the pharmacy information database to evaluate the X-level/contraindication and D-level/serious potential drug interactions (pDDIs) of outpatient anticoagulant prescriptions, so as to provide a guarantee for clinically safe drug use. METHODS: Based on the interaction of 5 oral anticoagulants recommended in the "China Guidelines for the Prevention and Treatment of Thrombotic Diseases (2018 Edition)" retrieved from the two databases of Lexicomp and Micromedex, statistics of a hospital from January 1,2021 to 2022 During March 31st,200 outpatients with anticoagulant prescriptions for grade X/contraindication and grade D/severe pDDIs were analyzed by multivariate Logistic binary regression analysis. RESULTS: Among the 200 athletic patients, there were 0 pairs of grade X/taboo pDDIs,and 67 pairs of grade D/severe pDDIs, mainly due to grade D/serious potential bleeding caused by the combination of anticoagulants and non-steroidal anti-inflammatory drugs(NSAIDs) risk. Multivariate Logistic binary regression analysis found that multiple drug combination (≥5 kinds) and concomitant cardiovascular disease were risk factors for the occurrence of grade D/severe pDDIs. CONCLUSION: for athletic patients with multiple diseases coexisting and needing to take multiple drugs, it is necessary to pay attention to the pDDIs of anticoagulant drugs, select appropriate drugs, and avoid fatal risks such as severe bleeding. Adverse reactions after medication were closely monitored. (AU)

An oral hydrogel carrier for delivering resveratrol into intestine-specific target released with high encapsulation efficiency and loading capacity based on structure-selected alginate and pectin.

Resveratrol (RES) has many beneficial effects on the human body, but it is always unstable, resulting in low oral bioavailability, especially in the gastrointestinal tract. In this study, we developed an oral intestine-specific released hydrogel carrier for targeted RES release in the intestinal tract, which was composed of alginate (ALG) with a specific ratio of α-L-guluronic (G blocks) and ß-D-mannuronic (M blocks) and low methoxyl pectin (LMP). The encapsulation efficiency and loading capacity of RES was 92.04 ± 0.32% and 6.41 ± 0.022 mg g-1 samples, respectively. Positioning release kinetics were investigated in vivo and in vitro. Also, this hydrogel carrier provides good protection for RES against the stomach. 94.71% of RES could be transported to the intestines in two hours after oral administration and released mainly in the small intestine and colon. Thus, the hydrogel carrier is conducive to RES, which is absorbed through the intestinal barrier rather than the stomach after oral administration. Moreover, the hydrogel carrier could load other health factors with expected encapsulation efficiencies, such as curcumin (93.52%), ascorbic acid (90.33%), ginsenoside Rg3 (81.54%), and EGCG (92.27%). These also implied that the hydrogel carrier holds general applicability in disease management.

Dietary intervention in depression - a review.

Depression is a mental illness that affects the normal lives of over 300 million people. Unfortunately, about 30% to 40% of patients do not adequately respond to pharmacotherapy and other therapies. This review focuses on exploring the relationship between dietary nutrition and depression, aiming to find safer and efficient ingredients to alleviate depression. Diet can affect depression in numerous ways. These pathways include the regulation of tryptophan metabolism, inflammation, hypothalamic-pituitary-adrenal (HPA) axis, microbe-gut-brain axis, brain-derived neurotrophic factor (BDNF) and epigenetics. Furthermore, probiotics, micronutrients, and other active substances exhibit significant antidepressant effects by regulating the above pathways. These provide insights for developing antidepressant foods.

Echinacoside (ECH) suppresses proliferation, migration, and invasion of human glioblastoma cells by inhibiting Skp2-triggered epithelial-mesenchymal transition (EMT).

BACKGROUND: Echinacoside (ECH) is a phenylethanoid extracted from the stems of Cistanches salsa, an herb used in Chinese medicine formulations, and is effective against glioblastoma multiforme (GBM). Epithelial-mesenchymal transition (EMT) is the cornerstone of tumorigenesis and metastasis, and increases the malignant behavior of GBM cells. The S phase kinase-related protein 2 (skp2), an oncoprotein associated with EMT, is highly expressed in GBM and significantly associated with drug resistance, tumor grade and dismal prognosis. The aim of this study was to explore the inhibitory effects of ECH against GBM development and skp2-induced EMT. METHODS: CCK-8, EdU incorporation, transwell, colony formation and sphere formation assays were used to determine the effects of ECH on GBM cell viability, proliferation, migration and invasion in vitro. The in vivo anti-glioma effects of ECH were examined using a U87 xenograft model. The expression levels of skp2 protein, EMT-associated markers (vimentin and snail) and stemness markers (Nestin and sox2) were analyzed by immunofluorescence staining and western blotting experiments. RESULTS: ECH suppressed the proliferation, invasiveness and migration of GBM cells in vitro, as well as the growth of U87 xenograft in vivo. In addition, ECH downregulated the skp2 protein, EMT-related markers (vimentin and snail) and stemness markers (sox2 and Nestin). The inhibitory effects of ECH were augmented in the skp2-knockdown GBM cells, and reversed in cells with ectopic expression of skp2. CONCLUSION: ECH inhibits glioma development by suppressing skp2-induced EMT of GBM cells.

Phytochemicals, Pharmacological Effects and Molecular Mechanisms of Mulberry.

There are numerous varieties of mulberry, and each has high medicinal value and is regarded as a promising source of traditional medicines and functional foods. Nevertheless, the nutrients and uses of mulberry differ from species (Morus alba L., Morus nigra L. and Morus rubra L.). Phenolic compounds are prominent among the biologically active ingredients in mulberry, especially flavonoids, anthocyanins and phenolic acids. Epidemiologic studies suggest that mulberry contains a rich, effective chemical composition and a wide range of biological activity, such as antioxidant, anti-inflammatory, anti-tumor and so on. However, compared with other berries, there has been a lack of systematic research on mulberry, and this hinders its further expansion as a functional fruit. The main purpose of this review is to provide the latest data regarding the effective chemical constituents and pharmacological effects of mulberry to support its further therapeutic potential and health functions.

Nifedipine or amlodipine? The choice for hypertension during pregnancy: a systematic review and meta-analysis.

BACKGROUND: There is a lack of sufficient evidence regarding efficacy and safety of amlodipine on treating hypertension during pregnancy. OBJECTIVE: To compare antihypertensive efficacy, pregnancy outcome and safety of amlodipine with nifedipine on hypertension during pregnancy. METHODS: A systematic search of PubMed, Embase, Cochrane Library, clinicaltrials.gov, Chinese National Knowledge Infrastructure, Wanfang Database and China Biology Medicine disc of randomized controlled trials (RCTs) up to April l5, 2021 was conducted on RCTs comparing amlodipine to nifedipine for the treatment of hypertension during pregnancy. Screening, data extraction, and quality assessment were done by two independent reviewers. To estimate relative effects from all available evidence, a meta-analysis was conducted. RESULTS: Seventeen RCTs were included. Amlodipine was found the efficacy is slightly superior to nifedipine on treating hypertension during pregnancy (RR 1.06, 95% CI 1.01 to 1.10) with a decreased risk for maternal side effects (RR 0.42, 95% CI 0.29 to 0.61). Subgroup analysis found amlodipine can get a better control on SBP (RR - 11.68, 95% CI - 17.98 to - 5.37) and DBP (RR - 7.44, 95% CI - 13.81 to - 1.06) compared with intermediate-/long-acting nifedipine. In addition, there was no difference between amlodipine and nifedipine on pregnancy outcomes including caesarean section, premature labour, placental abruption, FGR, fetal distress, neonatal asphyxia. CONCLUSIONS: Given the results of this systematic review and meta-analysis, amlodipine can be effectively and safely used for hypertension during pregnancy.

Correction: Bilberry anthocyanin improves the serum cholesterol in aging perimenopausal rats via the estrogen receptor signaling pathway.

Correction for 'Bilberry anthocyanin improves the serum cholesterol in aging perimenopausal rats via the estrogen receptor signaling pathway' by Na Li et al., Food Funct., 2019, 10, 3430-3438, DOI.

Correction: Poly(adenine)-mediated DNA-functionalized gold nanoparticles for sensitive detection of mercury ions in aqueous media.

[This corrects the article DOI: 10.1039/C9RA03041G.].

Lactobacillus rhamnosus LRa05 improves lipid accumulation in mice fed with a high fat diet via regulating the intestinal microbiota, reducing glucose content and promoting liver carbohydrate metabolism.

To elucidate the anti-obesity effect of Lactobacillus rhamnosus LRa05 through the analysis of gut microbiota and liver metabolomics, we investigated changes in gut microbiota and liver metabolomic phenotypes in mice by 16S ribosomal RNA gene sequencing and ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. C57BL/6J male mice were orally administered with LRa05 for 8 weeks. Body weight, serum lipid levels, and the lipid accumulation of liver cells and epididymal fat tissues in the mice fed with a high-fat diet were inhibited after treatment with LRa05 at 1 × 109 CFU per day per mouse. LRa05 also reshaped the gut microbiota, reduced the abundance of the pro-pathogen bacterial Streptococcus, suppressed blood and liver glucose content, and promoted liver carbohydrate and energy metabolism. Moreover, Intestinimonas and palmitoyl ethanolamide exhibited a positive correlation, whereas Enterorhabdus and vitamin B2 showed a negative correlation. Therefore, LRa05 can potentially be used as an anti-obesity probiotic in further interventions.

Leuconostoc pseudomesenteroides improves microbiota dysbiosis and liver metabolism imbalance and ameliorates the correlation between dihydroceramide and strains of Firmicutes and Proteobacteria in high fat diet obese mice.

Leuconostoc pseudomesenteroides is widely isolated from fermented foods; however, the underlying molecular mechanism behind its anti-obesity function has rarely been studied. This study aims to explore the role of alterations in gut microbes and liver metabolites mediated by Leuconostoc pseudomesenteroides (Tu) in obese mice for a period of 8 weeks through UPLC/Q-TOF-MS and 16S rRNA sequencing. Our results showed that Tu administration at a dosage of 1 × 109 CFU per day per mouse effectively attenuated the weight of mice, significantly reduced serum lipids, and markedly improved fecal lipid output. Tu also ameliorated the lipid profiles in the liver and epididymal fat tissues, and restored intestinal disorder caused by a high-fat diet. Moreover, glycerophospholipid metabolism in the liver was altered by increased dihydroceramide levels. Surprisingly, the correlation between dihydroceramide and strains of Firmicutes and Proteobacteria was found for the first time. Collectively, these findings highlight that Tu could be a potential dietary supplement for weight control.

Bifidobacterium longum subsp. longum Remodeled Roseburia and Phosphatidylserine Levels and Ameliorated Intestinal Disorders and liver Metabolic Abnormalities Induced by High-Fat Diet.

Bifidobacterium longum is considered as a potential supplement in antiobesity treatment; however, the underlying molecular mechanism has rarely been studied. To understand the contributions of B. longum subsp. longum (BL21) in the prevention of obesity, we investigated alterations in the liver metabonomic phenotype and gut microbiota by ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and 16S ribosomal RNA gene sequencing in C57BL/6J male mice orally administered with BL21 for 8 weeks [high-fat diet (HFD)]. BL21 at 1 × 109 CFU·day-1 per mouse reduced the weight of mice by 16.9% relative to that of the mice fed with HFD and significantly lowered the serum levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol. BL21 also ameliorated fat vacuolization in liver cells and epididymal fat accumulation. BL21 also lowered the Firmicutes/Bacteroidetes ratio, regulated liver remodeling in glycerophospholipids, and alleviated the levels of d-tryptophan. A positive correlation between the butyrate-producing strain Roseburia and the cell membrane component phosphatidylserine was found for the first time. Thus, BL21 can potentially prevent mice from being obese by rebalancing the gut microbiota and glycerophospholipid metabolism. BL21 can be a promising dietary supplement for weight control.

Capsanthin extract prevents obesity, reduces serum TMAO levels and modulates the gut microbiota composition in high-fat-diet induced obese C57BL/6J mice.

The present study investigated the anti-obesity effects and its mechanism of capsanthin (CAP) in high-fat diet-induced obese C57BL/6J mice. Compared with untreated mice on a high-fat diet for 12 weeks, CAP at 200 mg kg-1 reduced the body weight by 27.5%, significantly reversed glucose tolerance, effectively decreased the serum triglycerides, total cholesterol, low-density lipoprotein cholesterol, and trimethylamine N-oxide levels, markedly increased microbial diversity. Furthermore, 16S rRNA gene sequencing of the cecal microbiota suggested that CAP increased the abundance of Bacteroidetes, Bifidobacterium and Akkermansia, decreased the abundance of Ruminococcus and the ratio of Firmicutes/Bacteroidetes. Moreover, predicted functional domain analysis indicated that CAP increased the gene abundance of replication and repair, and decreased the gene abundance of membrane transports and carbohydrate metabolisms. Therefore, it seems CAP exhibit anti-obesity effect and might be used as a potential agent against obesity.

Astragaloside IV Protects Ethanol-Induced Gastric Mucosal Injury by Preventing Mitochondrial Oxidative Stress and the Activation of Mitochondrial Pathway Apoptosis in Rats.

Alcohol consumption affects gastric mucosa by multiple and complex mechanisms depending either by direct contact of ethanol or by indirect biological damage induced by its metabolite acetaldehyde. The present study aims at further investigating the mechanism of ethanol-induced gastric mucosa injury and the protective effect of astragaloside IV (AS-IV) in an aspect of mitochondrial oxidative stress and mitochondrial pathway of apoptosis. Using an array of experimental approaches, we have shown that the development of mitochondrial oxidative stress and associated apoptosis play crucial roles in the pathogenesis of gastric injury induced by ethanol. AS-IV inhibits mitochondrial oxidative stress by scavenging accumulation of malondialdehyde and decreasing the consumption of glutathione. AS-IV also prevents ethanol-induced apoptosis by modulating the activity of caspase-3 and caspase-9, the expression of Bax/Bcl-2, and the release of cytochrome C and apoptosis inducing factor. Moreover, AS-IV reduces ethanol-mediated activation of caspase-8 and breakage of Bid. This study thus indicates that AS-IV prevented ethanol-induced gastric damage by blocking activation of mitochondrial oxidative stress and mitochondrial pathway of apoptosis induced by ethanol in the gastric mucosa.

Bilberry anthocyanin improves the serum cholesterol in aging perimenopausal rats via the estrogen receptor signaling pathway.

With aging, there is an increasing risk for women to develop perimenopause syndrome, which is harmful to women's physical and mental health. The present study investigated the health benefits of bilberry anthocyanin (BA) on aging perimenopausal Sprague-Dawley rats. Rats that entered into perimenopause through natural aging were treated for 8 weeks with BA, and received either a low dose (LD, 35 mg per kg of bodyweight), medium dose (MD, 70 mg per kg of bodyweight), or high dose (HD, 140 mg per kg of bodyweight). The experimental results suggested that all three dosages of BA, especially the high dose, significantly reduced the serum total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) levels. In addition, BA supplementation markedly reduced the serum malondialdehyde (MDA), effectively increased the activity of hepatic total superoxide dismutase (T-SOD), significantly raised the high density lipoprotein cholesterol (HDL-C), increased the number of estrogen receptors, and effectively up-regulated the expression levels of G protein-coupled receptor 30 (GPR30), protein kinase B (AKT), and extracellular regulated protein kinase 2 (ERK2). In summary, BA has a great effect on improving the serum cholesterol in natural aging perimenopausal rats via the estrogen receptor signaling pathway, and it may be used as a dietary supplement for perimenopause women to decrease the risk of cardiovascular disease.

Poly(adenine)-mediated DNA-functionalized gold nanoparticles for sensitive detection of mercury ions in aqueous media.

In this work, a facile and sensitive colorimetric sensor for Hg2+ ions based on poly (adenine)-mediated DNA-functionalized gold nanoparticles (Au NPs) is reported. One DNA sequence consisting of poly-A and T-rich DNA was designed rationally. Poly-A was used as an anchoring block to bind tightly to Au NPs, and T-rich DNA was utilized for specific recognition of Hg2+ ions. With the assistance of poly-A, T-rich DNA was easily introduced onto the surface of Au NPs and kept an upright orientation. In the presence of Hg2+ ions, T base binding with Hg2+ ions results in the formation of "T-Hg2+-T" among the Au NPs, which caused aggregation of the Au NPs and a subsequent change in the color of the solution, from wine red to grayish blue. On this occasion, the limit of detection (LOD) was 3.75 nM Hg2+ ions with a linear range from 5 nM to 200 nM, as measured by UV-Vis spectroscopy. Moreover, successful application of this method for the detection of Hg2+ ions in real samples was demonstrated.

An Ultrasensitive Fluorescence Sensor with Simple Operation for Cu2+ Specific Detection in Drinking Water.

Whether short-term or long-term, overexposure to an abnormal amount of copper ion does significant harm to human health. Considering its nonbiodegradability, it is critical to sensitively detect copper ion. Herein, a novel fluorescent strategy with a "turn-on" signal was developed for highly sensitive and specific detection of copper ion (Cu2+). In the present investigation, we found that Cu2+ exhibits excellent peroxidase-like catalytic activity toward oxidizing the nonfluorescent substrate of Amplex Red into the product of resofurin with outstanding fluorescence emission under the aid of H2O2. Thus, an enzyme-free and label-free sensing system was constructed for copper ion detection with quite simple operation. To ensure the detection sensitivity and reproducibility, the amount of H2O2 and incubation time were optimized. The limit of detection can reach as low as 1.0 nM. In addition, the developed assay demonstrated excellent specificity and could be utilized to detect copper ion in water samples including tap water and bottled purified water without standing recovery.

Implementation of cascade logic gates and majority logic gate on a simple and universal molecular platform.

Wiring a series of simple logic gates to process complex data is significantly important and a large challenge for untraditional molecular computing systems. The programmable property of DNA endows its powerful application in molecular computing. In our investigation, it was found that DNA exhibits excellent peroxidase-like activity in a colorimetric system of TMB/H2O2/Hemin (TMB, 3,3', 5,5'-Tetramethylbenzidine) in the presence of K+ and Cu2+, which is significantly inhibited by the addition of an antioxidant. According to the modulated catalytic activity of this DNA-based catalyst, three cascade logic gates including AND-OR-INH (INHIBIT), AND-INH and OR-INH were successfully constructed. Interestingly, by only modulating the concentration of Cu2+, a majority logic gate with a single-vote veto function was realized following the same threshold value as that of the cascade logic gates. The strategy is quite straightforward and versatile and provides an instructive method for constructing multiple logic gates on a simple platform to implement complex molecular computing.

The effect of Astragaloside IV on ethanol-induced gastric mucosal injury in rats: Involvement of inflammation.

The present study aimed to investigate the potential protective effects of Astragaloside IV (AS-IV) against ethanol-induced gastric mucosal injury in rats. The animals were divided into 7 groups and pretreated with vehicle, various doses of AS-IV (1,2 and 4mg/kg, i.p.) or omeprazole (40mg/kg), 75min later, the gastric mucosal injury was induced by oral administration of ethanol. One hour after ethanol ingestion, the rats were euthanized and gastric tissues were collected to biochemical analyze. Myeloperoxidase (MPO), tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), interleukin 10 (IL-10), nuclear factor kappa B (NF-κB) p65 protein, TNF receptor-associated factor 2 (TRAF2) and nuclear NF-κB (nNF-κB) proteins were estimated by enzyme-linked immunosorbent assay or western blot analysis. The gastric mucosal lesions were assessed by macroscopic and histopathological examinations. The results showed pretreatment with AS-IV attenuated the severity of ethanol gastric mucosal damage as evidenced by lowering of injury scores, histopathologic aberrations and leukocyte invasion. These actions were analogous to the reference omeprazole. AS-IV suppressed gastric inflammation by curbing of MPO, TNF-α levels along with NF-κB p65 and TRAF2 expression. It also augmented the anti-inflammatory IL-10 levels. Meanwhile, AS-IV could inhibit NF-κB transcription by inhibiting the expression of NF-κB p65 and increasing the expression of nNF-κB. It seems that AS-IV as an anti-inflammatory agent may have a protective effect against ethanol-induced mucosal injury by inhibition of neutrophil infiltration and reducing the expression of NF-κB p65, TRAF2 and inflammatory cytokines via regulating TNF-α/NF-κB signal pathway in gastric tissue.

Anthocyanins in black rice, soybean and purple corn increase fecal butyric acid and prevent liver inflammation in high fat diet-induced obese mice.

Epidemiological evidence indicates that anthocyanin consumption reduces the incidence of chronic and degenerative diseases. Therefore, the present study aimed to determine whether black rice anthocyanin (BRA), black soybean anthocyanin (BSA), and purple corn anthocyanin (PCA) could mitigate oxidative stress and inflammation associated obesity in C57BL/6 mice fed with a high-fat diet. BRA, BSA, or PCA was administered at doses of 200 mg kg-1 throughout the 12-week experiment and reduced the bodyweight by 9.6%, 13.3%, or 16.6%, respectively. Furthermore, BRA, BSA or PCA administration could effectively increase fecal butyric acid levels, elevate hepatic SOD and GPx activities, decrease lipid peroxidation, and downregulate the gene expression levels of TNFα, IL-6, iNOS, and NF-κB. Hence, BRA, BSA, or PCA might ameliorate diet-induced obesity by alleviating both oxidative stress and inflammation.

Nanozyme-based bio-barcode assay for high sensitive and logic-controlled specific detection of multiple DNAs.

Since HCV and HIV share a common transmission path, high sensitive detection of HIV and HCV gene is of significant importance to improve diagnosis accuracy and cure rate at early stage for HIV virus-infected patients. In our investigation, a novel nanozyme-based bio-barcode fluorescence amplified assay is successfully developed for simultaneous detection of HIV and HCV DNAs with excellent sensitivity in an enzyme-free and label-free condition. Here, bimetallic nanoparticles, PtAuNPs, present outstanding peroxidase-like activity and act as barcode to catalyze oxidation of nonfluorescent substrate of amplex red (AR) into fluorescent resorufin generating stable and sensitive "Turn On" fluorescent output signal, which is for the first time to be integrated with bio-barcode strategy for fluorescence detection DNA. Furthermore, the provided strategy presents excellent specificity and can distinguish single-base mismatched mutant from target DNA. What interesting is that cascaded INHIBIT-OR logic gate is integrated with biosensors for the first time to distinguish individual target DNA from each other under logic function control, which presents great application in development of rapid and intelligent detection.