Effect of uric acid reduction on chronic kidney disease. Systematic review and meta-analysis
Accumulating evidence suggests that hyperuricemia is a pathological factor in the development and progression of chronic kidney disease. However, the potential benefit afforded by the control of uric acid (UA) is controversial. Individual studies show discrepant results, and most existing meta-analysis, especially those including the larger number of studies, lack a placebo or control group as they aim to compare efficacy between drugs. On these grounds, we performed a me-ta-analysis restricted to studies including the action of any anti-gout therapies referenced to a control or placebo arm. This approach allows for a clea...
Source: Frontiers in Pharmacology - March 26, 2024 Category: Drugs & Pharmacology Source Type: research

Unveiling the anticancer effects of SGLT-2i: mechanisms and therapeutic potential
Cancer and diabetes are significant diseases that pose a threat to human health. Their interconnection is complex, particularly when they coexist, often necessitating multiple therapeutic approaches to attain remission. Sodium-glucose cotransporter protein two inhibitors (SGLT-2i) emerged as a treatment for hyperglycemia, but subsequently exhibited noteworthy extra-glycemic properties, such as being registered for the treatment of heart failure and chronic kidney disease, especially with co-existing albuminuria, prompting its assessment as a potential treatment for various non-metabolic diseases. Considering its overall to...
Source: Frontiers in Pharmacology - March 26, 2024 Category: Drugs & Pharmacology Source Type: research

Optimum programmed intermittent epidural bolus interval time of ropivacaine 0.0625% with dexmedetomidine 0.4  μg/ml at a fixed volume of 10 mL: a randomized controlled trial
Conclusion:The estimated value for EI90 for PIEB between boluses of ropivacaine 0.0625% with dexmedetomidine 0.4 μg/ml at a fixed volume of 10 mL using probit regression was 45.4 (35.5–50.5) minutes. Furthermore, future studies are warranted to be established to determine the optimal parameters for different regimens in clinical practice. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 26, 2024 Category: Drugs & Pharmacology Source Type: research

Dosing optimization of rituximab for primary membranous nephropathy by population pharmacokinetic and pharmacodynamic study
Primary membranous nephropathy (PMN) is the most common cause for adult nephrotic syndrome. Rituximab has demonstrated promising clinical efficacy by random controlled trials and the off-label use is widely adopted in PMN. However, the standard dosage is borrowed from B cell lymphoma treatment with far more antigens and is oversaturated for PMN treatment, accompanied with additional safety risk and unnecessary medical cost. More than 15% serious adverse events were observed under standard dosage and low dose therapies were explored recently. Dose optimization by clinical trials is extremely time- and cost-consuming and can...
Source: Frontiers in Pharmacology - March 26, 2024 Category: Drugs & Pharmacology Source Type: research

Quercetin reshapes gut microbiota homeostasis and modulates brain metabolic profile to regulate depression-like behaviors induced by CUMS in rats
This study aimed to investigate the therapeutic effects of quercetin on chronic unpredictable mild stress (CUMS)-induced depression-like behaviors in rats and explore the underlying mechanisms by combining untargeted metabolomics and 16S rRNA sequencing analysis of brain tissue metabolites and gut microbiota. Gut microbiota analysis revealed that at the phylum level, quercetin reduced Firmicutes and the Firmicutes/Bacteroidetes (F/B) ratio and enhanced Cyanobacteria. At the genus level, quercetin downregulated 6 and upregulated 14 bacterial species. Metabolomics analysis revealed that quercetin regulated multiple metabolic...
Source: Frontiers in Pharmacology - March 26, 2024 Category: Drugs & Pharmacology Source Type: research

Cost-effectiveness of immune checkpoint inhibitors in treating metastatic urothelial cancer
Conclusion: Our real-world data suggests that first line use of ICI combined with chemotherapy demonstrates better cost-effectiveness and similar survival outcomes for mUC patients, when compared with subsequent ICI therapy after chemotherapy. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 26, 2024 Category: Drugs & Pharmacology Source Type: research

Phytocompounds targeting epigenetic modulations: an assessment in cancer
For centuries, plants have been serving as sources of potential therapeutic agents. In recent years, there has been a growing interest in investigating the effects of plant-derived compounds on epigenetic processes, a novel and captivating Frontier in the field of epigenetics research. Epigenetic changes encompass modifications to DNA, histones, and microRNAs that can influence gene expression. Aberrant epigenetic changes can perturb key cellular processes, including cell cycle control, intercellular communication, DNA repair, inflammation, stress response, and apoptosis. Such disruptions can contribute to cancer developme...
Source: Frontiers in Pharmacology - March 26, 2024 Category: Drugs & Pharmacology Source Type: research

Pharmacological enhancement of cholinergic neurotransmission alleviates neuroinflammation and improves functional outcomes in a triple transgenic mouse model of Alzheimer ’s disease
In conclusion, chronic treatment with α-GPC exhibited a significant anti-inflammatory activity and sustained the key function of hippocampal synapses, crucial for the maintenance of a regular cognitive status. In light of our results, we suggest that α-GPC could be exploited as a promising therapeutic approach in early phases of AD. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 26, 2024 Category: Drugs & Pharmacology Source Type: research

Estimating preferences and willingness to pay for pharmacogenetic testing in populations who are medically underserved: a discrete choice experiment
Conclusion: This first-of-its-kind study provides important insights into the willingness to pay for PGx testing and PGx test preferences of a large medically underserved population. Applying these findings can potentially lead to improvements in the successful implementation of PGx testing in this population. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 26, 2024 Category: Drugs & Pharmacology Source Type: research

The effect of oral butyrate on colonic short-chain fatty acid transporters and receptors depends on microbial status
Butyrate, a metabolite produced by gut bacteria, has demonstrated beneficial effects in the colon and has been used to treat inflammatory bowel diseases. However, the mechanism by which butyrate operates remains incompletely understood. Given that oral butyrate can exert either a direct impact on the gut mucosa or an indirect influence through its interaction with the gut microbiome, this study aimed to investigate three key aspects: (1) whether oral intake of butyrate modulates the expression of genes encoding short-chain fatty acid (SCFA) transporters (Slc16a1, Slc16a3, Slc16a4, Slc5a8, Abcg2) and receptors (Hcar2, Ffar2...
Source: Frontiers in Pharmacology - March 26, 2024 Category: Drugs & Pharmacology Source Type: research

Design and synthesis of novel dihydropyridine- and benzylideneimine-based tyrosinase inhibitors
Tyrosinase (TYR) inhibitors are very significant as they inhibit enzyme tyrosinase activity, and its inhibition is vital for skin care, anticancer medication, and antibrowning of fruits and vegetables. This work presents a novel and economical route for the preparation of new synthetic tyrosinase inhibitors using amlodipine (4). The novel conjugates 6 (a–o) were designed, synthesized, and characterized by spectroscopic analyses, including Fourier transform infrared and low- and high-resolution mass spectroscopy. The purified compound 4 was refluxed with various aldehydes and ketones 5 (a–o) for 5–8 h in methanol at ...
Source: Frontiers in Pharmacology - March 26, 2024 Category: Drugs & Pharmacology Source Type: research

Mechanisms of Bushenyiqi decoction in the treatment of asthma: an investigation based on network pharmacology with experimental validation
Conclusion: In conclusion, the integration of network pharmacology and biological experiments has demonstrated that key constituents of BYD, such as quercetin, kaempferol, and luteolin, exhibit targeted effects on IL-6, EGFR, and HIF1A in combating asthma-related inflammation through inhibition of the PI3K/AKT signaling pathway. The findings of this investigation provide evidence supporting the effectiveness of TCM’s “bushenyiqi” therapy in asthma management, as corroborated by contemporary medical technology. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 25, 2024 Category: Drugs & Pharmacology Source Type: research

Kinetic modeling of the plasma pharmacokinetic profiles of ADAMTS13 fragment and its Fc-fusion counterpart in mice
This study applied kinetic modeling to gain insights into the cellular processing contributing to the observed pharmacokinetic (PK) differences between the novel recombinant ADAMTS13 fragment (MDTCS) and its Fc-fusion protein (MDTCS-Fc).Methods: For MDTCS and MDTCS-Fc, their plasma PK profiles were obtained at two dose levels following intravenous administration of the respective proteins to mice. The plasma PK profiles of MDTCS were fitted to a kinetic model with three unknown protein-dependent parameters representing the fraction recycled (FR) and the rate constants for endocytosis (kup, for the uptake into the endosomes...
Source: Frontiers in Pharmacology - March 25, 2024 Category: Drugs & Pharmacology Source Type: research

Paucatalinone A from Paulownia Catalpifolia Gong Tong Elicits mitochondrial-mediated cancer cell death to combat osteosarcoma
This study underscores the potential of Paucatalinone A in initiating apoptosis in cancer cells and highlights the therapeutic efficacy of plant-derived agents in treating osteosarcoma, offering a viable approach for managing other intractable cancers. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 25, 2024 Category: Drugs & Pharmacology Source Type: research

Comprehensive effect of Naoxintong capsule combined with Western medicine on coronary heart disease after percutaneous coronary intervention: a meta-analysis
Conclusion:A combination of NXT and WM can improve clinical outcomes in patients undergoing PCI. However, further studies are needed to confirm the reliability and safety of this combined treatment approach.Systematic Review Registration:PROSPERO, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=369174, Identifier CRD42022369174. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - March 25, 2024 Category: Drugs & Pharmacology Source Type: research