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Pharmacological Research Jan 2023Cucurbitacin B (CuB, CHO), the most abundant and active member of cucurbitacins, which are highly oxidized tetracyclic triterpenoids. Cucurbitacins are widely... (Review)
Review
Cucurbitacin B (CuB, CHO), the most abundant and active member of cucurbitacins, which are highly oxidized tetracyclic triterpenoids. Cucurbitacins are widely distributed in a variety of plants and mainly isolated from plants in the Cucurbitaceae family. CuB is mostly obtained from the pedicel of Cucumis melo L. Modern pharmacological studies have confirmed that CuB has a broad range of pharmacological activities, with significant therapeutic effects on a variety of diseases including inflammatory diseases, neurodegenerative diseases, diabetes mellitus, and cancers. In this study the PubMed, Web of Science, Science Direct, and China National Knowledge Infrastructure (CNKI) databases were searched from 1986 to 2022. After inclusion and exclusion criteria were applied, 98 out of 2484 articles were selected for a systematic review to comprehensively summarize the pharmacological activity, toxicity, and pharmacokinetic properties of CuB. The results showed that CuB exhibits potent anti-inflammatory, antioxidant, antiviral, hypoglycemic, hepatoprotective, neuroprotective, and anti-cancer activities mainly via regulating various signaling pathways, such as the Janus kinase/signal transducer and activator of transcription-3 (JAK/STAT3), nuclear factor erythroid 2-related factor-2/antioxidant responsive element (Nrf2/ARE), nuclear factor (NF)-κB, AMP-activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/Akt, cancerous inhibitor of protein phosphatase-2A/protein phosphatase-2A (CIP2A/PP2A), Wnt, focal adhesion kinase (FAK), Notch, and Hippo-Yes-associated protein (YAP) pathways. Studies of its toxicity and pharmacokinetic properties showed that CuB has non-specific toxicity and low bioavailability. In addition, derivatives and clinical applications of CuB are discussed in this paper.
Topics: Cucurbitacins; Protein Phosphatase 2; Antioxidants; Phosphatidylinositol 3-Kinases; Triterpenes; NF-kappa B
PubMed: 36460279
DOI: 10.1016/j.phrs.2022.106587 -
Seizure Nov 2020Lamotrigine (LTG) is a new generation antiepileptic drug. However, relatively high interindividual pharmacokinetic variability of this drug has been documented.... (Review)
Review
BACKGROUND
Lamotrigine (LTG) is a new generation antiepileptic drug. However, relatively high interindividual pharmacokinetic variability of this drug has been documented. Therefore, several population pharmacokinetic studies of lamotrigine were conducted to identify factors influencing its pharmacokinetics.
OBJECTIVE
This systematic review aimed to summarize significant factors influencing LTG pharmacokinetics and their relationships with pharmacokinetic parameters as well as the magnitude of pharmacokinetic variability.
METHODS
Four databases i.e. PubMed, Scopus, CINAHL Complete, and Science Direct were systematically searched from their inception to March 2020. Population pharmacokinetic studies of LTG conducted in humans using a nonlinear-mixed effect approach were eligible for a systematic review.
RESULTS
Nineteen studies were included in this systematic review. Most studies characterized LTG pharmacokinetics as a one-compartment model structure. The three most frequently identified significant covariates influencing LTG clearance included concomitant antiepileptic drugs, body weight, and genetic polymorphisms. Approximately 58% of the studies did not externally validate the models.
CONCLUSIONS
For clinical application, LTG maintenance dose could be optimized using population pharmacokinetic models employing covariates such as concomitant antiepileptic drugs, body weight, and genetic polymorphisms. However, these models should be assessed for their predictability in the target population before utilizing such models in clinical settings.
Topics: Anticonvulsants; Body Weight; Humans; Lamotrigine; Triazines
PubMed: 33060011
DOI: 10.1016/j.seizure.2020.07.014 -
Journal of Clinical Medicine Feb 2022: Assessing the abuse potential of new substances with central nervous system activity is essential for preventing possible risks of misuse and addiction. The same... (Review)
Review
: Assessing the abuse potential of new substances with central nervous system activity is essential for preventing possible risks of misuse and addiction. The same methodology is recommended for the evaluation of the abuse potential of recreational drugs. This systematic review aims to assess the pharmacological effects related to the abuse potential and pharmacokinetics of cathinones, which are evaluated in both experimental and prospective observational studies in humans. : A systematic search of the published literature was conducted to retrieve studies that had administered cathinone, mephedrone, methylone, and diethylpropion to evaluate their acute pharmacological effects related to abuse potential. : The search yielded 583 results, 18 of which were included to assess the abuse potential of cathinone ( = 5), mephedrone ( = 7), methylone ( = 1), and diethylpropion ( = 5). All four substances induce stimulant and euphorigenic effects that resemble those of amphetamines and MDMA, and their different intensities may be associated with varying levels of abuse potential. : Cathinone, mephedrone, methylone, and diethylpropion induce a range of desirable and reinforcing effects that may, to some extent, result in abuse potential. Further investigation is needed to minimize and prevent their impact on society and public health.
PubMed: 35207278
DOI: 10.3390/jcm11041004 -
Biomolecules Nov 2022The antioxidant activity of protein-derived peptides was one of the first to be revealed among the more than 50 known peptide bioactivities to date. The exploitation... (Review)
Review
The antioxidant activity of protein-derived peptides was one of the first to be revealed among the more than 50 known peptide bioactivities to date. The exploitation value associated with food-derived antioxidant peptides is mainly attributed to their natural properties and effectiveness as food preservatives and in disease prevention, management, and treatment. An increasing number of antioxidant active peptides have been identified from a variety of renewable sources, including terrestrial and aquatic organisms and their processing by-products. This has important implications for alleviating population pressure, avoiding environmental problems, and promoting a sustainable shift in consumption. To identify such opportunities, we conducted a systematic literature review of recent research advances in food-derived antioxidant peptides, with particular reference to their biological effects, mechanisms, digestive stability, and bioaccessibility. In this review, 515 potentially relevant papers were identified from a preliminary search of the academic databases PubMed, Google Scholar, and Scopus. After removing non-thematic articles, articles without full text, and other quality-related factors, 52 review articles and 122 full research papers remained for analysis and reference. The findings highlighted chemical and biological evidence for a wide range of edible species as a source of precursor proteins for antioxidant-active peptides. Food-derived antioxidant peptides reduce the production of reactive oxygen species, besides activating endogenous antioxidant defense systems in cellular and animal models. The intestinal absorption and metabolism of such peptides were elucidated by using cellular models. Protein hydrolysates (peptides) are promising ingredients with enhanced nutritional, functional, and organoleptic properties of foods, not only as a natural alternative to synthetic antioxidants.
Topics: Animals; Antioxidants; Biological Availability; Peptides; Protein Hydrolysates; Food Handling; Food Additives
PubMed: 36358972
DOI: 10.3390/biom12111622 -
British Journal of Clinical Pharmacology Jul 2020This is a PROSPERO registered systematic review (CRD42018105207), conducted to summarize the available knowledge regarding the population pharmacokinetics of digoxin in... (Review)
Review
This is a PROSPERO registered systematic review (CRD42018105207), conducted to summarize the available knowledge regarding the population pharmacokinetics of digoxin in paediatrics and to identify the sources of variability in its disposition. PubMed, ISI Web of Science, SCOPUS and Science Direct databases were searched from inception to January 2019. All paediatric population pharmacokinetic studies of digoxin that utilized the nonlinear mixed-effect modelling approach were incorporated in this review, and data were synthesized descriptively. After application of the inclusion-exclusion criteria 8 studies were included. Most studies described digoxin pharmacokinetics as a 1-compartment model with only 1 study describing its pharmacokinetics as 2-compartments. Age was an important predictor of clearance in studies involving neonates or infants, other predictors of clearance were weight, height, serum creatinine, coadministration of spironolactone and presence of congestive heart failure. Congestive heart failure was also associated with an increased volume of distribution in 1 study. The estimated value of apparent clearance in a typical individual standardized by mean weight ranged between 0.24 and 0.56 L/h/kg, the interindividual variability in clearance ranged between 7.0 and 35.1%. Half of the studies evaluated the performance of their developed models via external evaluation. In conclusion, substantial predictors of digoxin pharmacokinetics in the paediatric population in addition to model characteristics and evaluation techniques are presented. For clinicians, clearance could be predicted using age especially in neonates or infants, weight, height, serum creatinine, coadministration of medications and disease status. For future researchers, designing pharmacokinetic studies that allow 2-compartment modelling and linking pharmacokinetics with pharmacodynamics is recommended.
Topics: Child; Digoxin; Heart Failure; Humans; Infant; Infant, Newborn; Models, Biological; Nonlinear Dynamics; Pediatrics; Spironolactone
PubMed: 32153059
DOI: 10.1111/bcp.14272 -
Frontiers in Endocrinology 2023The performance in evaluating thyroid nodules on ultrasound varies across different risk stratification systems, leading to inconsistency and uncertainty regarding... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The performance in evaluating thyroid nodules on ultrasound varies across different risk stratification systems, leading to inconsistency and uncertainty regarding diagnostic sensitivity, specificity, and accuracy.
OBJECTIVE
Comparing diagnostic performance of detecting thyroid cancer among distinct ultrasound risk stratification systems proposed in the last five years.
EVIDENCE ACQUISITION
Systematic search was conducted on PubMed, EMBASE, and Web of Science databases to find relevant research up to December 8, 2022, whose study contents contained elucidation of diagnostic performance of any one of the above ultrasound risk stratification systems (European Thyroid Imaging Reporting and Data System[Eu-TIRADS]; American College of Radiology TIRADS [ACR TIRADS]; Chinese version of TIRADS [C-TIRADS]; Computer-aided diagnosis system based on deep learning [S-Detect]). Based on golden diagnostic standard in histopathology and cytology, single meta-analysis was performed to obtain the optimal cut-off value for each system, and then network meta-analysis was conducted on the best risk stratification category in each system.
EVIDENCE SYNTHESIS
This network meta-analysis included 88 studies with a total of 59,304 nodules. The most accurate risk category thresholds were TR5 for Eu-TIRADS, TR5 for ACR TIRADS, TR4b and above for C-TIRADS, and possible malignancy for S-Detect. At the best thresholds, sensitivity of these systems ranged from 68% to 82% and specificity ranged from 71% to 81%. It identified the highest sensitivity for C-TIRADS TR4b and the highest specificity for ACR TIRADS TR5. However, sensitivity for ACR TIRADS TR5 was the lowest. The diagnostic odds ratio (DOR) and area under curve (AUC) were ranked first in C-TIRADS.
CONCLUSION
Among four ultrasound risk stratification options, this systemic review preliminarily proved that C-TIRADS possessed favorable diagnostic performance for thyroid nodules.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, CRD42022382818.
Topics: Humans; Thyroid Nodule; Network Meta-Analysis; Thyroid Neoplasms; Area Under Curve
PubMed: 37720531
DOI: 10.3389/fendo.2023.1227339 -
Evidence-based Complementary and... 2020Fritillariae Cirrhosae Bulbus (known as chuanbeimu in Chinese, FCB) is a famous folk medicine which has been widely used to relieve cough and eliminate phlegm for... (Review)
Review
Fritillariae Cirrhosae Bulbus (known as chuanbeimu in Chinese, FCB) is a famous folk medicine which has been widely used to relieve cough and eliminate phlegm for thousands of years in China. The medicine originates from dried bulbs of six species of which are distributed in the temperate zone of the Northern Hemisphere. Increasing attention has been paid to FCB because of its excellent medicinal value such as being antitussive, expectorant, analgesic, anticancer, anti-inflammatory, and antioxidative. During the past years, a large number of research studies have been conducted to investigate the phytochemistry, pharmacology, and pharmacokinetics of FCB. A range of compounds have been isolated and identified from FCB, including alkaloids, saponins, nucleosides, organic acids, terpenoids, and sterols. Among them, alkaloids as the main active ingredient have been illustrated to exert significant therapeutic effects on many diseases such as cancer, acute lung injury, chronic obstructive pulmonary disease, asthma, Parkinson's disease, and diabetes. Due to the excellent medical value and low toxicity, FCB has a huge market all over the world and triggers a growing enthusiasm among researchers. However, there is still a lack of systematic review. Hence, in this work, we reviewed the FCB-based articles published in Sci Finder, Web of Science, PubMed, Google Scholar, CNKI, and other databases in the recent years. The traditional uses, sources, phytochemistry, pharmacology, pharmacokinetics, and toxicity of FCB were discussed in the review, which aims to provide a reference for further development and utilization of FCB.
PubMed: 33273948
DOI: 10.1155/2020/1536534 -
European Journal of Medicinal Chemistry Jan 2024Prostate specific membrane antigen (PSMA) has been the subject of several studies in recent decades as a promising molecular target for prostate cancer (PCa), in fact it... (Review)
Review
Prostate specific membrane antigen (PSMA) has been the subject of several studies in recent decades as a promising molecular target for prostate cancer (PCa), in fact it is considered an excellent molecular target for both PCa imaging (both for staging and follow-up), by means of PET/CT and for radioligand therapy. Its interesting molecular features have enabled the development of a new diagnostic and therapeutic approach for PCa, called "theranostics." Considering the abundance of PSMA-based probes that have appeared so far in the literature, the present work focuses the attention on radiopharmaceuticals with increasing clinical application, highlighting advantages and disadvantages in terms of different metabolization and excretion processes, pharmacokinetic, binding affinity and variable internalization rate, tumor-to-background ratio, residence times and toxicity profile.
Topics: Male; Humans; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms; Radiopharmaceuticals; Precision Medicine; Gallium Radioisotopes
PubMed: 37992520
DOI: 10.1016/j.ejmech.2023.115966 -
Antibiotics (Basel, Switzerland) Sep 2023Cephalexin is a first-generation β-lactam antibiotic used in adults and pediatrics to treat various streptococcal and staphylococcal infections. This review aims to... (Review)
Review
Cephalexin is a first-generation β-lactam antibiotic used in adults and pediatrics to treat various streptococcal and staphylococcal infections. This review aims to summarize and evaluate all the pharmacokinetic (PK) data on cephalexin by screening out all pertinent studies in human beings following the per oral (PO) route. By employing different online search engines such as Google Scholar, PubMed, Cochrane Central, and Science Direct, 23 studies were retrieved, among which nine were in healthy subjects, five in diseased ones, and the remaining were drug-drug, drug-food, and bioequivalence-related. These studies were included only based on the presence of plasma concentration-time profiles or PK parameters, i.e., maximum plasma concentration (C), half-life (t) area under the curve from time 0-infinity (AUC and clearance (CL/F). A dose-proportional increase in AUC and C can be portrayed in different studies conducted in the healthy population. In comparison to cefaclor, C was recorded to be 0.5 folds higher for cephalexin in the case of renal impairment. An increase in AUC was seen in cephalexin on administration with probenecid, i.e., 117 µg.h/mL vs. 68.1 µg.h/mL. Moreover, drug-drug interactions with omeprazole, ranitidine, zinc sulfate, and drug-food interactions for cephalexin and other cephalosporins have also been depicted in different studies with significant changes in all PK parameters. This current review has reported all accessible studies containing PK variables in healthy and diseased populations (renal, dental, and osteoarticular infections, continuous ambulatory peritoneal dialysis) that may be favorable for health practitioners in optimizing doses among the latter.
PubMed: 37760698
DOI: 10.3390/antibiotics12091402 -
Frontiers in Public Health 2023Variants in organic cation transporter (OCT) genes play a crucial role in metformin pharmacokinetics and are critical for diabetes treatment. However, studies... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Variants in organic cation transporter (OCT) genes play a crucial role in metformin pharmacokinetics and are critical for diabetes treatment. However, studies investigating the effect of OCT genetic polymorphisms on metformin response have reported inconsistent results. This review and meta-analysis aimed to evaluate the associations between OCT genetic polymorphisms and metformin response and intolerance in individuals with type 2 diabetes mellitus (T2DM).
METHOD
A systematic search was conducted on PubMed, EMBASE, CNKI, WANFANG DATA, and VIP database for identifying potential studies up to 10 November 2022. The Q-Genie tool was used to evaluate the quality of included studies. Pooled odds ratios (OR) or standardized mean differences (SMD) and 95% confidence intervals (95% CI) were calculated to determine the associations between OCT genetic polymorphisms and metformin response and intolerance that were reflected by glycemic response indexes, such as glycated hemoglobin level (HbA1c%) or change in glycated hemoglobin level (ΔHbA1c%), fasting plasma level (FPG) or change in fasting plasma glucose level (ΔFPG), the effectiveness rate of metformin treatment, and the rate of metformin intolerance. A qualitative review was performed for the variants identified just in one study and those that could not undergo pooling analysis.
RESULTS
A total of 30 related eligible studies about OCT genes (, and ) and metformin pharmacogenetics were identified, and 14, 3, and 6 single nucleotide polymorphisms (SNPs) in , and , respectively, were investigated. Meta-analysis showed that the rs622342 polymorphism was associated with a reduction in HbA1c level (AA vs. AC: SMD [95% CI] = -0.45 [-0.73--0.18]; = 0.001). The GG genotype of the rs628031 polymorphism was associated with a reduction in FPG level (GG vs. AA: SMD [95 %CI] = -0.60 [-1.04-0.16], = 0.007; GG vs. AG: -0.45 [-0.67-0.20], < 0.001). No statistical association was found between the remaining variants and metformin response and intolerance.
CONCLUSION
rs622342 and rs628031 polymorphisms were potentially associated with glycemic response to metformin. This evidence may provide novel insight into gene-oriented personalized medicine for diabetes.
Topics: Humans; Metformin; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Hypoglycemic Agents; Polymorphism, Single Nucleotide; Cations
PubMed: 37546319
DOI: 10.3389/fpubh.2023.1183879