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World Journal of Surgical Oncology Jan 2024We aimed to provide a reference based on evidence for an individualized clinical medication of high-dose methotrexate (HD-MTX) in osteosarcoma patients by evaluating the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We aimed to provide a reference based on evidence for an individualized clinical medication of high-dose methotrexate (HD-MTX) in osteosarcoma patients by evaluating the effect of gene polymorphism on adverse reactions of HD-MTX usage.
METHODS
Several databases were combed for research on the association between gene polymorphisms and adverse reactions to HD-MTX up to January 2023. A meta-analysis and/or descriptive analysis on the incidence of HD-MTX-related adverse reactions were conducted by using clinical studies meeting inclusion criteria.
RESULTS
Twelve studies involving 889 patients were included. There were 8, 6, 5, and 4 studies related to MTHFR C677T, MTHFR A1298C, RFC1 G80A, and MDR1 C3435T polymorphisms, respectively. The results of the meta-analysis showed that the MTHFR C677T polymorphism was associated with G3-4 hepatotoxicity, G3-4 nephrotoxicity, G3-4 gastrointestinal toxicity, and G3-4 mucositis under the recessive genetic model (MM vs. Mm/mm). Limited research showed that MTHFR C677T was associated with G3-4 nephrotoxicity in the allelic genetic model (M vs. m). MTHFR A1298C polymorphism was associated with a decreased risk of adverse reactions to HD-MTX usage, without statistical significance. This review's descriptive analysis showed no significant correlation between the RFC1 G80A, and MDR1 C3435T polymorphism and adverse reactions of HD-MTX.
CONCLUSION
The MTHFR C677T mutation may enhance the risk of HD-MTX adverse reactions in osteosarcoma patients. Existing studies have not found a significant correlation between the MTHFR A1298C, RFC1 G80A, and MDR1 C3435T polymorphism and adverse reactions caused by HD-MTX. Lastly, this conclusion was limited because of few studies.
Topics: Humans; Methotrexate; Polymorphism, Genetic; Alleles; Methylenetetrahydrofolate Reductase (NADPH2); Osteosarcoma; Polymorphism, Single Nucleotide; Genotype
PubMed: 38212758
DOI: 10.1186/s12957-023-03287-0 -
Journal of Sport and Health Science Jul 2024The ergogenic effects of caffeine intake on exercise performance are well-established, even if differences exist among individuals in response to caffeine intake. The... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The ergogenic effects of caffeine intake on exercise performance are well-established, even if differences exist among individuals in response to caffeine intake. The genetic variation of a specific gene, human cytochrome P450 enzyme 1A2 (CYP1A2) (rs762551), may be one reason for this difference. This systematic review and meta-analysis aimed to comprehensively evaluate the influence of CYP1A2 gene types on athletes' exercise performance after caffeine intake.
METHODS
A literature search through 4 databases (Web of Science, PubMed, Scopus, and China National Knowledge Infrastructure) was conducted until March 2023. The effect size was expressed as the weighted mean difference (WMD) by calculating fixed effects meta-analysis if heterogeneity was not significant (I ≤ 50% and p ≥ 0.1). Subgroup analyses were performed based on AA and AC/CC genotype of CYP1A2.
RESULTS
The final number of studies meeting the inclusion criteria was 12 (n = 666 participants). The overall analysis showed that the cycling time trial significantly improved after caffeine intake (WMD = -0.48, 95% confidence interval (95%CI): -0.83 to -0.13, p = 0.007). In subgroup analyses, acute caffeine intake improved cycling time trial only in individuals with the A allele (WMD = -0.90, 95%CI: -1.48 to -0.33, p = 0.002), but not the C allele (WMD = -0.08, 95%CI: -0.32 to 0.17, p = 0.53). Caffeine supplementation did not influence the Wingate (WMD = 8.07, 95%CI: -22.04 to 38.18, p = 0.60) or countermovement jump test (CMJ) performance (WMD = 1.17, 95%CI: -0.02 to 2.36, p = 0.05), and these outcomes were not influenced by CYP1A2 genotype.
CONCLUSION
Participants with the CYP1A2 genotype with A allele improved their cycling time trials after caffeine supplementation. However, compared to placebo, acute caffeine supplementation failed to increase the Wingate or CMJ performance, regardless of CYP1A2 genotype.
Topics: Cytochrome P-450 CYP1A2; Humans; Caffeine; Athletic Performance; Performance-Enhancing Substances; Genotype; Dietary Supplements; Bicycling
PubMed: 38158179
DOI: 10.1016/j.jshs.2023.12.005 -
Endocrine Apr 2024Subacute thyroiditis (SAT) is a transient inflammatory disorder of the thyroid gland with a possible viral etiology. We conducted this study to estimate the pooled... (Meta-Analysis)
Meta-Analysis
PURPOSE
Subacute thyroiditis (SAT) is a transient inflammatory disorder of the thyroid gland with a possible viral etiology. We conducted this study to estimate the pooled prevalence of thyroid autoantibodies in SAT patients. This question arose due to the varying reports on the positivity rates of thyroid autoantibodies among SAT patients.
METHODS
We searched PubMed, Embase, Scopus, and Web of Science from their inception until March 25th, 2023. Observational studies reporting the positivity rate of thyroid autoantibodies for more than ten patients were included. We used the Joanna Briggs Institute's (JBI) critical appraisal checklist to assess the quality of the included studies. Pooled prevalence estimates with 95% confidence intervals were calculated using the random effects model. Subgroup analyses were performed to find sources of heterogeneity.
RESULTS
Out of 1373 identified records, 32 studies involving 2348 SAT patients were included in our study. Thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) were positive in 22.8% and 12.2% of patients, respectively. The Study design, mean erythrocyte sedimentation rate and mean thyroid-stimulating hormone of patients were identified as sources of heterogeneity. As our secondary objectives, we found a recurrence rate of 14.7% and permanent hypothyroidism in 11.6% of patients.
CONCLUSION
The results of our study revealed a low TPOAb positivity rate in SAT patients, consistent with its non-autoimmune etiology. The TgAb positivity rate in SAT patients was higher than that of the general population, possibly explained by the transient release of thyroglobulin into the bloodstream during the thyrotoxic phase, leading to subsequent TgAb production. Furthermore, our findings demonstrate a notable recurrence rate and permanent hypothyroidism among SAT patients, highlighting the importance of ongoing follow-up care.
Topics: Humans; Autoantibodies; Hypothyroidism; Iodide Peroxidase; Prevalence; Thyroglobulin; Thyroiditis, Subacute
PubMed: 38147263
DOI: 10.1007/s12020-023-03655-6 -
International Journal of Dermatology Apr 2024Skin is a major site of cortisol bioconversion by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzymes which catalyze intracellular inactive cortisone into... (Review)
Review
Skin is a major site of cortisol bioconversion by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzymes which catalyze intracellular inactive cortisone into physiologically active cortisol. 11β-HSD1 is highly expressed in skin, especially in dermal fibroblasts, epidermal keratinocytes, melanocytes, and hair follicles, and plays important roles in regulating keratinocytes, fibroblast proliferation, and has roles in skin aging. Inhibition of 11β-HSD1 may reverse decreased collagen levels observed in extrinsically and intrinsically aged skin. Inhibitors of 11β-HSD1 may also have the potential to reverse decreased collagen observed in skin atrophy induced by glucocorticoid treatment. This systematic review aimed to summarize the current knowledge of roles for 11β-HSD1 inhibitor in skin physiology and potential for future use in medications. Studies have demonstrated that immediately following experimental insult in an animal model, there is increased expression of 11β-HSD1, and that topical application of an 11β-HSD1 inhibitor increases the rate of healing, increases skin collagen content, increases dermal fibroblasts, and increases dermal thickness. Furthermore, in patients with type 2 diabetes mellitus, 11β-HSD1 inhibitors reduce wound diameter after injury. Further development of 11β-HSD1 inhibitors appears to be a promising area for treating aging skin, aiding wound healing, and mitigating effects of systemic glucocorticoid use. Both topically and orally administered 11β-HSD1 inhibitors appear to be viable avenues for future research.
Topics: Animals; Humans; Aged; 11-beta-Hydroxysteroid Dehydrogenase Type 1; Glucocorticoids; Hydrocortisone; Diabetes Mellitus, Type 2; Collagen; Skin Aging
PubMed: 38146184
DOI: 10.1111/ijd.16967 -
Expert Review of Clinical Pharmacology Jan 2024Quetiapine exhibits notable pharmacokinetic and pharmacodynamic (PK/PD) variability, the origins of which are poorly understood. This systematic review summarizes... (Review)
Review
INTRODUCTION
Quetiapine exhibits notable pharmacokinetic and pharmacodynamic (PK/PD) variability, the origins of which are poorly understood. This systematic review summarizes published population PK/PD studies and identifies significant covariates accounting for this variability to inform precision dosing.
METHODS
We systematically searched the PubMed, Web of Science, and Embase databases and compared study characteristics, model parameters, and covariate effects. Visual predictive distributions were used to compare different models. Forest plots and Monte Carlo simulations were used to assess the influence of covariates.
RESULTS
Six population PK and three population PK/PD studies were included. The median apparent clearance in adults was 87.7 L/h. Strong and moderate cytochrome P450 3A4 inducers increased the apparent clearance approximately fourfold, while strong cytochrome P450 3A4 inhibitors reduced it by 93%. The half-maximum effect concentrations were 82.8 ng/mL for the Brief Psychiatric Rating Scale and 583 ng/mL for dopamine D receptor occupancy. Both treatment duration and quetiapine exposure were associated with weight gain.
CONCLUSIONS
Concurrent administration of potent or moderate CYP3A4 inducers and inhibitors need to be avoided in quetiapine-treated patients. When co-medication is required, it is recommended to adjust the dosage based on therapeutic drug monitoring. Additional research is warranted to delineate the dose-exposure-response relationships of quetiapine and active metabolite norquetiapine in pediatrics, geriatrics, hepatically-impaired patients, and women using contraceptives or are pregnant or menopausal.
PROSPERO REGISTRATION
CRD42023446654.
Topics: Adult; Humans; Female; Child; Quetiapine Fumarate; Cytochrome P-450 Enzyme System; Models, Biological
PubMed: 38108086
DOI: 10.1080/17512433.2023.2295428 -
The Journal of Maternal-fetal &... Dec 2023Three common endothelial nitric oxide synthase (eNOS) gene variants are existed such as; G-894T, T-786C, and variable number tandem repeats in intron-4 (VNTR intron-4)... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Three common endothelial nitric oxide synthase (eNOS) gene variants are existed such as; G-894T, T-786C, and variable number tandem repeats in intron-4 (VNTR intron-4) which has been proposed to be linked with PE. However, there is still debate regarding the findings. To address this, a review was conducted to assess the potential association of eNOS gene variants at these positions with the risk of PE.
METHODS
PubMed, Scopus, Science Direct, Hinari, and African Journal Online databases and Google Scholar search engines were utilized to search studies published in English-language until 30 January 2023. The Joanna Briggs Institute Meta-Analysis instrument was used for data extraction process and the Newcastle-Ottawa Scale was used to appraise the quality of the included studies. Meta-regression analysis was conducted using Stata 14 statistical software. The pooled odds ratios (ORs) of fixed and random effect models were utilized to evaluate the association of eNOS gene polymorphism with the risk of PE at 95% CI. Publication bias was assessed using Egger's test and a funnel plot.
RESULTS
The study included 47 observational studies involving 13,795 pregnant women (6216 cases and 7579 controls). Pregnant women carrying TT and CC genotypes of eNOS gene at 894 and 786 positions were found to have a greater probability of developing PE as compared to GG and TT genotypes (OR = 1.54 vs. 1.43 and CI: 1.12 - 2.14 vs.1.02 - 2.00 at 95% CI), respectively. However, a significant association was not observed between aa genotype of eNOS gene in VNTR intron-4 region and risk of PE as compared to bb genotype (OR =1.26, 95% CI: 0.83 - 1.89). The allelic model of eNOS gene at all positions showed nonsignificant association with the risk of PE.
CONCLUSIONS
The women having eNOS gene variants at 894 and 786 positions showed a significant association with the risk of PE. Yet, the women having eNOS gene variant at intron-4 region showed nonsignificant association with the risk of PE. Thus, this study suggests that eNOS gene variants may play a role in the development of PE, but large-scale studies are required to inaugurate concrete evidence on the roles of eNOS gene variants in PE pathogenesis.
Topics: Female; Humans; Pregnancy; Case-Control Studies; Genetic Predisposition to Disease; Genotype; Nitric Oxide Synthase Type III; Polymorphism, Genetic; Pre-Eclampsia
PubMed: 38086755
DOI: 10.1080/14767058.2023.2290918 -
Anti-inflammatory & Anti-allergy Agents... 2023Previous studies have experimentally validated and reported that chemical constituents of marine sponges are a source of natural anti-inflammatory substances with the...
BACKGROUND
Previous studies have experimentally validated and reported that chemical constituents of marine sponges are a source of natural anti-inflammatory substances with the biotechnological potential to develop novel drugs.
AIMS
Therefore, the aim of this study was to perform a systematic review to provide an overview of the anti-inflammatory substances isolated from marine sponges with therapeutic potential.
METHODS
This systematic review was performed on the Embase, PubMed, Scopus and Web of Science electronic databases. In total, 613 were found, but 340 duplicate studies were excluded, only 100 manuscripts were eligible, and 83 were included.
RESULTS
The results were based on and assays, and the anti-inflammatory effects of 251 bioactive compounds extracted from marine sponges were investigated. Their anti-inflammatory activities include inhibition of pro-inflammatory mediators, such as tumor necrosis factor- α (TNF-α), interleukin-6 (IL-6), nitrite or nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin 1β (IL-1β), prostaglandin E2 (PGE2), phospholipase A2 (PLA2), nuclear transcription factor-kappa B (NF-κB), leukotriene B4 (LTB4), cyclooxygenase- 1 (COX-1), and superoxide radicals.
CONCLUSION
In conclusion, data suggest (approximately 98% of articles) that substances obtained from marine sponges may be promising for the development of novel anti-inflammatory drugs for the treatment of different pathological conditions.
Topics: Animals; NF-kappa B; Anti-Inflammatory Agents; Interleukin-6; Tumor Necrosis Factor-alpha; Porifera; Lipopolysaccharides; Nitric Oxide Synthase Type II; Cyclooxygenase 2; Nitric Oxide
PubMed: 38038014
DOI: 10.2174/0118715230272152231106094727 -
Medicinal Research Reviews Mar 2024Lysine-specific demethylase 1 (LSD1) is a flavin adenine dinucleotide (FAD) dependent monoamine oxidase (MAO) that erases the mono-, and dimethylation of histone 3... (Review)
Review
Lysine-specific demethylase 1 (LSD1) is a flavin adenine dinucleotide (FAD) dependent monoamine oxidase (MAO) that erases the mono-, and dimethylation of histone 3 lysine 4 (H3K4), resulting in the suppression of target gene transcriptions. Besides, it can also demethylate some nonhistone substrates to regulate their biological functions. As reported, LSD1 is widely upregulated and plays a key role in several kinds of cancers, pharmacological or genetic ablation of LSD1 in cancer cells suppresses cell aggressiveness by several distinct mechanisms. Therefore, numerous LSD1 inhibitors, including covalent and noncovalent, have been developed and several of them have entered clinical trials. Herein, we systemically reviewed and discussed the biological function of LSD1 in tumors, lymphocytes as well as LSD1-targeting inhibitors in clinical trials, hoping to benefit the field of LSD1 and its inhibitors.
Topics: Humans; Lysine; Histone Demethylases; Monoamine Oxidase Inhibitors; Histones; Neoplasms; Drug Discovery; Enzyme Inhibitors
PubMed: 38014919
DOI: 10.1002/med.22000 -
Epilepsia Feb 2024Antiseizure medications (ASMs) are commonly categorized as enzyme-inducers and non-enzyme-inducers based on their propensity to enhance the metabolism of concomitantly... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Antiseizure medications (ASMs) are commonly categorized as enzyme-inducers and non-enzyme-inducers based on their propensity to enhance the metabolism of concomitantly administered drugs. This systematic review and network meta-analysis aimed to rank ASMs as cytochrome P450 3A (CYP3A)-inducers based on a comparative assessment of ASM-induced reduction in the concentrations of sensitive substrate drugs.
METHODS
The protocol was registered with PROSPERO (International Prospective Register of Systematic Reviews; CRD42022335846), and the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) standards were followed. We searched MEDLINE, Embase, and Cochrane until March 14, 2023 without an initial date restriction. Data were additionally obtained via the US Food and Drug Administration database. Studies had to be prospective, with ASM monotherapy for ≥5 days. The primary parameter was the magnitude of change in the area under the concentration-time curve of CYP3A substrates following treatment with the ASM. The standardized mean difference (SMD) was used as the point estimate for the indirect comparisons between ASMs using the pairwise method. Bias risk was assessed using the PKclin tool.
RESULTS
We identified 14 open-label, fixed-sequence studies with 370 participants. The effect size of 600 mg/day carbamazepine did not differ from those of 300 mg/day phenytoin (SMD = -.06, 95% confidence interval [CI] = -.18 to .07) and 200 mg/day cenobamate (SMD = -.11, 95% CI = -.26 to .04). Carbamazepine at 600 mg/day was the strongest CYP3A-inducer (P-score = .88), followed by carbamazepine 400 mg/day (.83), phenytoin 300 mg/day (.79), and cenobamate 200 mg/day (.73). Eslicarbazepine (800 mg/day) ranked higher than cenobamate 100 mg/day and oxcarbazepine 900 mg/day (.60, .39, and .37, respectively).
SIGNIFICANCE
Despite the limited number of studies, our network meta-analysis emphasizes that the magnitude of ASM effects on CYP3A substrate metabolism is a dose-dependent continuum. When possible, ASM classification as inducers should apply cutoff values tailored to the outcome. Prescribers should monitor plasma concentrations or clinical effects of CYP3A substrates and consider selecting concomitant medications accordingly.
Topics: Humans; Cytochrome P-450 CYP3A; Phenytoin; Network Meta-Analysis; Pharmaceutical Preparations; Carbamazepine; Benzodiazepines; Carbamates; Chlorophenols; Tetrazoles
PubMed: 38010146
DOI: 10.1111/epi.17822 -
CNS Drugs Nov 2023In Parkinson's disease, safinamide and zonisamide are novel monoamine oxidase-B inhibitors with a dual mechanism of action involving the inhibition of sodium and calcium... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
In Parkinson's disease, safinamide and zonisamide are novel monoamine oxidase-B inhibitors with a dual mechanism of action involving the inhibition of sodium and calcium channels and the subsequent release of glutamate. The aim of this systematic review and meta-analysis was to examine the efficacy and safety of both drugs compared with placebo on motor symptoms, cognitive function, and quality of life in patients with Parkinson's disease.
METHODS
We searched MEDLINE, EMBASE, Cochrane Central, Scopus, PsycINFO, and trials registries up to March 2023 for randomized controlled trials of adults with Parkinson's disease administered either safinamide or zonisamide and published in English. We excluded single-arm trials or if neither the efficacy nor safety outcomes of interest were reported. Primary outcomes were the change from baseline in Unified Parkinson's Disease Rating Scale section III (UPDRS-III) and serious adverse events. Secondary outcomes included a change from baseline in OFF-time, Parkinson's Disease Questionnaire 39 to evaluate quality of life, and Mini-Mental State Examination for cognitive function assessment. The meta-analysis was conducted using Review Manager 5.4.1. Random-effect models were used to calculate the pooled mean differences (MDs) and risk ratios with 95% confidence intervals (CIs). Subgroup analyses by medication, doses, Parkinson's disease stage, and risk of bias were conducted. We assessed the risk of bias using the Cochrane's risk of bias tool. Sensitivity analysis was conducted, and publication bias were evaluated. This meta-analysis was not externally funded, and the protocol is available on the Open Science Framework Registration ( https://doi.org/10.17605/OSF.IO/AMNP5 ).
RESULTS
Of 3570 screened citations, 16 trials met inclusion criteria (4314 patients with Parkinson's disease). Ten safinamide trials were conducted in several countries. Six zonisamide trials were included, five of which were conducted in Japan and one in India. UPDRS Part III scores were significantly lower with both monoamine oxidase-B inhibitors than with placebo (MD = - 2.18; 95% CI - 2.88 to - 1.49; I =63%; n = 14 studies). A subgroup analysis showed a significant improvement in UPDRS-III in safinamide (MD = - 2.10; 95% CI - 3.09 to - 1.11; I = 71%; n = 8 studies) and zonisamide (MD = - 2.31; 95% CI - 3.35 to - 1.27; I = 52%; n = 6 studies) compared with placebo. Monoamine oxidase-B inhibitors significantly decreased OFF-time compared with placebo. No significant differences in cognitive function (Mini-Mental State Examination), whereas an improvement in quality of life (Parkinson's Disease Questionnaire 39 scores) was observed. There was no significant difference in incidence rates of serious adverse events among all examined doses of zonisamide and safinamide compared with placebo. Two trials were reported as a high risk of bias and sensitivity analyses confirmed the primary analysis results.
CONCLUSIONS
Evidence suggests that novel monoamine oxidase-B inhibitors not only improve motor symptoms but also enhance patients' quality of life. The meta-analysis showed that both medications have a similar safety profile to placebo with regard to serious adverse events. The overall findings emphasize the effectiveness of safinamide and zonisamide in the treatment of Parkinson's disease as adjunct therapy. Further long-term studies examining the impact of these medications on motor and non-motor symptoms are necessary.
Topics: Adult; Humans; Parkinson Disease; Zonisamide; Quality of Life; Randomized Controlled Trials as Topic; Dopamine Agents; Monoamine Oxidase
PubMed: 37973769
DOI: 10.1007/s40263-023-01048-x