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BMC Gastroenterology May 2024Proton-pump inhibitors (PPIs) prevent aspirin-associated gastric and duodenal mucosal damage. However, long-term use of PPIs can lead to various adverse reactions, such...
BACKGROUND
Proton-pump inhibitors (PPIs) prevent aspirin-associated gastric and duodenal mucosal damage. However, long-term use of PPIs can lead to various adverse reactions, such as gastric polyps and enterochromaffin-like cell hyperplasia. Current research indicates that the abovementioned adverse reactions are mainly related to hypergastrinemia. We investigated whether low-frequency administration of omeprazole could effectively repair aspirin-induced mucosal damage and reduce the increase in gastrin levels associated with long-term use of PPIs.
METHODS
Sprague‒Dawley rats were divided into four treatment groups: daily aspirin, daily aspirin and omeprazole once every day (qd), daily aspirin and omeprazole once every other day (qod), and daily aspirin and omeprazole once every three days (1/d3). After 15 days of feeding, blood samples were collected, and the stomachs of sacrificed rats were subjected to macroscopic, histological, and immunohistochemical studies. Moreover, in clinical practice, patients with peptic ulcers caused by aspirin took a standard dose of omeprazole (20 mg) every other day. Two months later, gastroscopy was performed to examine the healing of the ulcers.
RESULTS
Both the omeprazole qd and omeprazole qod administrations effectively prevented aspirin-induced gastric peptic ulcers, with no significant difference between the two groups in the inhibition of parietal cell secretion of gastric acid and cell apoptosis. However, omeprazole 1/d3 failed to completely prevent aspirin-induced gastric mucosal injury. Notably, the gastrin levels, cell proliferation ability and cholecystokinin B receptor expression of the omeprazole qd group were significantly higher than those of the omeprazole qod group. In clinical work, patients with peptic ulcers caused by aspirin were given a standard dose of omeprazole every other day, and their ulcers healed after 2 months, as observed by gastroscopy.
CONCLUSIONS
Omeprazole administration once every other day can effectively prevent aspirin-induced peptic ulcers and reduce hypergastrinemia, which may reduce the long-term adverse effects of PPI treatment.
Topics: Animals; Aspirin; Omeprazole; Rats, Sprague-Dawley; Proton Pump Inhibitors; Gastric Mucosa; Gastrins; Male; Rats; Drug Administration Schedule; Humans; Peptic Ulcer; Intestinal Mucosa; Stomach Ulcer
PubMed: 38811868
DOI: 10.1186/s12876-024-03265-0 -
Scientific Reports May 2024Hemoglobin A (HbA) plays a crucial role in diabetes management. We aimed to evaluate the analytical performance of a new enzymatic method kit for HbA measurement. The...
Hemoglobin A (HbA) plays a crucial role in diabetes management. We aimed to evaluate the analytical performance of a new enzymatic method kit for HbA measurement. The performance of the enzymatic method, including precision, accuracy, and linearity, was evaluated. Moreover, the interference effect from conventional interferents, Hb derivatives, Hb variants, and common drugs were assessed. In addition, the agreement of HbA results was compared between enzymatic methods, cation-exchange high-performance liquid chromatography (HPLC), and immunoassays. The intra-assay, between-assay, and total precision of HbA were all lower than 2%. HbA showed good linearity within the range of 3.96-20.23%. The enzymatic assay yielded results consistent with the external quality control samples, with a bias of less than ± 6% from the target values. The enzymatic method showed no interference from bilirubin, intralipid, vitamin C, Hb derivatives, common Hb variants, as well as antipyretic analgesics and hypoglycemic drugs. The HbA results of the enzymatic assay showed good agreement and accuracy compared to those obtained from the HPLC method and the immunoassay. The enzymatic method kit performed on the BS-600M chemistry analyzer is a reliable and robust method for measuring HbA. It is suitable for routine practice in clinical chemistry laboratories.
Topics: Glycated Hemoglobin; Humans; Enzyme Assays; Chromatography, High Pressure Liquid; Reproducibility of Results; Immunoassay; Diabetes Mellitus
PubMed: 38811684
DOI: 10.1038/s41598-024-63261-y -
JACC. Cardiovascular Interventions May 2024
Topics: Humans; Aspirin; Drug Administration Schedule; Hemorrhage; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 38811106
DOI: 10.1016/j.jcin.2024.04.020 -
Pharmacological Research Jul 2024Coronavirus disease 2019 (COVID-19) affected people worldwide, and fever is one of the major symptoms of this disease. Although Acetaminophen (APAP) is a common...
Coronavirus disease 2019 (COVID-19) affected people worldwide, and fever is one of the major symptoms of this disease. Although Acetaminophen (APAP) is a common fever-reducing medication, it can also mediate liver injury. However, the role of PGC-1α in regulating mitochondrial quality control by lactate dehydrogenase B (LDHB), a vital enzyme catalyzing the conversion of lactate to pyruvate, in APAP-induced hepatotoxicity, is unclear. Here, gene expression omnibus data of patients with APAP-induced liver injury were used to explore gene expression profiles. AML12 cells and C57/BL6 mice were used to establish models of APAP-induced acute liver injury. SIRT1 and PGC-1α were overexpressed in vitro via lentiviral transfection to establish stable cell lines. The results showed that APAP treatment decreased SIRT1/PGC-1α/LDHB expression and increased protein lactylation, mitochondrial lactate levels, and pathological damage in liver mitochondria. PGC-1α upregulation or activation ameliorated APAP-induced damage in the cells and liver. Furthermore, PGC-1α overexpression increased LDHB synthesis, reduced lactylation, and induced a switch from lactate to pyruvate production. These results suggest that PGC-1α and LDHB play a role in APAP-induced liver injury by regulating mitochondrial quality control and lactate metabolic reprogramming. Therefore, the PGC-1α/LDHB axis is a potential therapeutic target for APAP-induced liver injury.
Topics: Animals; Acetaminophen; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Chemical and Drug Induced Liver Injury; Mice, Inbred C57BL; Mice; Humans; Male; L-Lactate Dehydrogenase; Lactic Acid; Mitochondrial Proteins; Cell Line; Mitochondria, Liver; Sirtuin 1; Isoenzymes
PubMed: 38810904
DOI: 10.1016/j.phrs.2024.107228 -
Science Advances May 2024Regular, long-term aspirin use may act synergistically with genetic variants, particularly those in mechanistically relevant pathways, to confer a protective effect on...
Regular, long-term aspirin use may act synergistically with genetic variants, particularly those in mechanistically relevant pathways, to confer a protective effect on colorectal cancer (CRC) risk. We leveraged pooled data from 52 clinical trial, cohort, and case-control studies that included 30,806 CRC cases and 41,861 controls of European ancestry to conduct a genome-wide interaction scan between regular aspirin/nonsteroidal anti-inflammatory drug (NSAID) use and imputed genetic variants. After adjusting for multiple comparisons, we identified statistically significant interactions between regular aspirin/NSAID use and variants in 6q24.1 (top hit ), which has evidence of influencing expression of TBC1D7 (a subunit of the TSC1-TSC2 complex, a key regulator of MTOR activity), and variants in 5p13.1 (top hit ), which is associated with expression of PTGER4 (codes a cell surface receptor directly involved in the mode of action of aspirin). Genetic variants with functional impact may modulate the chemopreventive effect of regular aspirin use, and our study identifies putative previously unidentified targets for additional mechanistic interrogation.
Topics: Humans; Colorectal Neoplasms; Anti-Inflammatory Agents, Non-Steroidal; Genome-Wide Association Study; Polymorphism, Single Nucleotide; Aspirin; Receptors, Prostaglandin E, EP4 Subtype; Male; Genetic Predisposition to Disease; Female; Case-Control Studies; Middle Aged; Genetic Loci; Aged
PubMed: 38809988
DOI: 10.1126/sciadv.adk3121 -
Cell Communication and Signaling : CCS May 2024The SARS-CoV-2 virus causes severe COVID-19 in one-fifth of patients. In addition to high mortality, infection may induce respiratory failure and cardiovascular...
BACKGROUND
The SARS-CoV-2 virus causes severe COVID-19 in one-fifth of patients. In addition to high mortality, infection may induce respiratory failure and cardiovascular complications associated with inflammation. Acute or prolonged inflammation results in organ fibrosis, the cause of which might be endothelial disorders arising during the endothelial-mesenchymal transition (EndMT).
METHODS
HUVECs and HMEC-1 cells were stimulated with SARS-CoV-2 S (Spike) and N (Nucleocapsid) proteins, and EndMT induction was evaluated by studying specific protein markers via Western blotting. Wound healing and tube formation assays were employed to assess the potential of SARS-CoV-2 to stimulate changes in cell behaviour. MRTF nuclear translocation, ROS generation, TLR4 inhibitors, TGF-β-neutralizing antibodies, and inhibitors of the TGF-β-dependent pathway were used to investigate the role of the TGF-β-MRTF signalling axis in SARS-CoV-2-dependent EndMT stimulation.
RESULTS
Both viral proteins stimulate myofibroblast trans-differentiation. However, the N protein is more effective at EndMT induction. The TGF-β-MRTF pathway plays a critical role in this process. The N protein preferentially favours action through TGF-β2, whose secretion is induced through TLR4-ROS action. TGF-β2 stimulates MRTF-A and MRTF-B nuclear translocation and strongly regulates EndMT. In contrast, the Spike protein stimulates TGF-β1 secretion as a result of ACE2 downregulation. TGF-β1 induces only MRTF-B, which, in turn, weakly regulates EndMT. Furthermore, aspirin, a common nonsteroidal anti-inflammatory drug, might prevent and reverse SARS-CoV-2-dependent EndMT induction through TGF-β-MRTF pathway deregulation.
CONCLUSION
The reported study revealed that SARS-CoV-2 infection induces EndMT. Moreover, it was demonstrated for the first time at the molecular level that the intensity of the EndMT triggered by SARS-CoV-2 infection may vary and depend on the viral protein involved. The N protein acts through TLR4-ROS-TGF-β2-MRTF-A/B, whereas the S protein acts through ACE2-TGF-β1-MRTF-B. Furthermore, we identified aspirin as a potential anti-fibrotic drug for treating patients with SARS-CoV-2 infection.
Topics: Humans; Spike Glycoprotein, Coronavirus; SARS-CoV-2; Transforming Growth Factor beta; COVID-19; Coronavirus Nucleocapsid Proteins; Aspirin; Signal Transduction; Epithelial-Mesenchymal Transition; Human Umbilical Vein Endothelial Cells; Transcription Factors; Toll-Like Receptor 4; Cell Line; Endothelial-Mesenchymal Transition; Phosphoproteins
PubMed: 38807115
DOI: 10.1186/s12964-024-01665-z -
Journal of the American Heart... Jun 2024ADP and ATP are importantly involved in vascular and thrombotic homeostasis, via multiple receptor pathways. Blockade of ADP P2Y receptors inhibits platelet aggregation... (Randomized Controlled Trial)
Randomized Controlled Trial
Safety, Tolerability, and Pharmacodynamics of AZD3366 (Optimized Human CD39L3 Apyrase) Alone and in Combination With Ticagrelor and Acetylsalicylic Acid: A Phase 1, Randomized, Placebo-Controlled Study.
BACKGROUND
ADP and ATP are importantly involved in vascular and thrombotic homeostasis, via multiple receptor pathways. Blockade of ADP P2Y receptors inhibits platelet aggregation and represents an effective cardiovascular disease prevention strategy. AZD3366 (APT102), a long-acting recombinant form of an optimized CD39L3 human apyrase, has effectively reduced ATP, ADP, and platelet aggregation and provided tissue protection in preclinical models, features that could be very beneficial in treating patients with cardiovascular disease.
METHODS AND RESULTS
We conducted this phase 1, first-in-human study of single ascending doses of intravenous AZD3366 or placebo, including doses added to dual antiplatelet therapy with ticagrelor and acetylsalicylic acid. The primary objective was safety and tolerability; secondary and exploratory objectives included pharmacokinetics, pharmacodynamics (measured as inhibition of platelet aggregation), adenosine diphosphatase (ADPase) activity, and ATP/ADP metabolism. In total, 104 participants were randomized. AZD3366 was generally well tolerated, with no major safety concerns observed. ADPase activity increased in a dose-dependent manner with a strong correlation to AZD3366 exposure. Inhibition of ADP-stimulated platelet aggregation was immediate, substantial, and durable. In addition, there was a prompt decrease in systemic ATP concentration and an increase in adenosine monophosphate concentrations, whereas ADP concentration appeared generally unaltered. At higher doses, there was a prolongation of capillary bleeding time without detectable changes in the ex vivo thromboelastometric parameters.
CONCLUSIONS
AZD3366 was well tolerated in healthy participants and demonstrated substantial and durable inhibition of platelet aggregation after single dosing. Higher doses prolonged capillary bleeding time without detectable changes in ex vivo thromboelastometric parameters.
REGISTRATION
URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04588727.
Topics: Humans; Male; Ticagrelor; Female; Apyrase; Platelet Aggregation; Aspirin; Platelet Aggregation Inhibitors; Middle Aged; Adult; Double-Blind Method; Dual Anti-Platelet Therapy; Drug Therapy, Combination; Young Adult; Adenosine Diphosphate; Blood Platelets; Dose-Response Relationship, Drug; Treatment Outcome; Recombinant Proteins; Purinergic P2Y Receptor Antagonists
PubMed: 38804212
DOI: 10.1161/JAHA.123.033985 -
Frontiers in Pharmacology 2024Cong-Chi decoction (CCD) is made using L. (shallot) bulbs and Sojae Semen Praeparatum (SSP). Shallot bulbs and SSP are both used regularly in traditional Chinese...
BACKGROUND
Cong-Chi decoction (CCD) is made using L. (shallot) bulbs and Sojae Semen Praeparatum (SSP). Shallot bulbs and SSP are both used regularly in traditional Chinese medicine; however, there are no recent pharmacological studies on their synergistic effects. Despite their roles in the treatment of the common cold for thousands of years, their pharmacological mechanisms of action against wind-cold-type common cold are yet to be explored comprehensively.
METHODS
A mouse model was standardized using wind-cold modeling equipment to study the anti-inflammatory, antioxidant, and antiapoptotic effects of CCD. Then, 16S rRNA sequencing was employed to analyze the association between and changes in body temperature. Additionally, the antipyretic effects of were validated via animal experiments.
RESULTS
The results indicate that CCD improves the symptoms of wind-cold by reducing fever, levels of pro-inflammatory factors, and cellular apoptosis, as well as increasing the blood leukocyte and lymphocyte counts, thereby alleviating lung tissue damage. The effects of CCD are mediated by upregulation of pulmonary Nrf2 and HO-1 expressions, thereby reducing oxidative damage in the lungs, in addition to other anti-inflammatory mechanisms. Furthermore, CCD increases the abundance of in the intestinal tract. The animal experiments confirm that ameliorates fever in mice.
CONCLUSION
CCD exhibits remarkable antioxidant and anti-inflammatory properties for effectively treating wind-cold-type common cold. Furthermore, its regulatory effects on represent a novel mechanism for product development.
PubMed: 38803435
DOI: 10.3389/fphar.2024.1364328 -
Pharmaceuticals (Basel, Switzerland) May 2024Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely utilized pharmaceuticals worldwide. Besides their recognized anti-inflammatory effects, these... (Review)
Review
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely utilized pharmaceuticals worldwide. Besides their recognized anti-inflammatory effects, these drugs exhibit various other pleiotropic effects in several cells, including platelets. Within this article, the multifaceted properties of NSAIDs on platelet functions, activation and viability, as well as their interaction(s) with established antiplatelet medications, by hindering several platelet agonists' pathways and receptors, are thoroughly reviewed. The efficacy and safety of NSAIDs as adjunctive therapies for conditions involving inflammation and platelet activation are also discussed. Emphasis is given to the antiplatelet potential of commonly administered NSAIDs medications, such as ibuprofen, diclofenac, naproxen and ketoprofen, alongside non-opioid analgesic and antipyretic medications like paracetamol. This article delves into their mechanisms of action against different pathways of platelet activation, aggregation and overall platelet functions, highlighting additional health-promoting properties of these anti-inflammatory and analgesic agents, without neglecting the induced by these drugs' side-effects on platelets' functionality and thrombocytopenia. Environmental issues emerging from the ever-increased subscription of these drugs are also discussed, along with the need for novel water treatment methodologies for their appropriate elimination from water and wastewater samples. Despite being efficiently eliminated during wastewater treatment processes on occasion, NSAIDs remain prevalent and are found at significant concentrations in water bodies that receive effluents from wastewater treatment plants (WWTPs), since there is no one-size-fits-all solution for removing all contaminants from wastewater, depending on the specific characteristics of the wastewater. Several novel methods have been studied, with adsorption being proposed as a cost-effective and environmentally friendly method for wastewater purification from such drugs. This article also presents limitations and future prospects regarding the observed antiplatelet effects of NSAIDs, as well as the potential of novel derivatives of these compounds, with benefits in other important platelet functions.
PubMed: 38794197
DOI: 10.3390/ph17050627 -
Sensors (Basel, Switzerland) May 2024The purpose of this paper is to demonstrate a new discovery regarding the interaction between materials and very low radio frequencies. Specifically, we observed a...
The purpose of this paper is to demonstrate a new discovery regarding the interaction between materials and very low radio frequencies. Specifically, we observed a feedback response on an inertia active sensor when specific frequencies (around 2-4 kHz) are used to irradiate targeted pharmaceutical samples like aspirin or paracetamol drugs. The characteristics of this phenomenon, such as excitation and relaxation time, the relation between deceleration and a material's quantity, and signal amplitude, are presented and analyzed. Although the underlying physics of this phenomenon is not yet known, we have shown that it has potential applications in remote identification of compounds, detection, and location sensing, as well as identifying substances that exist in plants without the need for any processing. This method is fast, accurate, low-cost, non-destructive, and non-invasive, making it a valuable area for further research that could yield spectacular results in the future.
Topics: Acetaminophen; Electromagnetic Phenomena; Aspirin; Pharmaceutical Preparations; Radio Waves
PubMed: 38793913
DOI: 10.3390/s24103059