Front Pharmacol. 2025 Jan 3;15:1540478. doi: 10.3389/fphar.2024.1540478. eCollection 2024.

NO ABSTRACT

PMID:39830351 | PMC:PMC11739166 | DOI:10.3389/fphar.2024.1540478

Front Pharmacol. 2025 Jan 3;15:1526101. doi: 10.3389/fphar.2024.1526101. eCollection 2024.

ABSTRACT

INTRODUCTION: The field of pharmacogenetics (PGx) is experiencing significant growth, with increasing evidence to support its application in psychiatric care, suggesting its potential to personalize treatment plans, optimize medication efficacy, and reduce adverse drug reactions. However, the perceived utility and practicability of PGx for psychiatric treatment in youth remains underexplored. This study investigated perceived barriers and attitudes in Australian young adults towards the implementation of PGx testing to guide antidepressant treatment in primary care.

METHODS: Semi-structured focus groups and interviews were conducted with 17 participants aged between 18 and 24 years. These sessions were recorded and transcribed before thematic analysis was used to identify collective themes.

RESULTS: Three key themes were identified, including attitudes towards the medication prescription process, concerns and attitudes towards PGx testing, and perceived barriers to its clinical implementation. Although PGx testing was positively perceived by most participants, all participants shared concerns about PGx testing. Participants voiced concerns about the financial impact of PGx testing, the potential for treatment delays, and the accuracy of PGx testing in guiding antidepressant treatment. Additionally, participants noted that the low awareness and willingness of general practitioners to incorporate PGx testing into routine practice could hinder successful clinical implementation.

DISCUSSION: Prior to the implementation of PGx testing into Australian primary practices, it is essential to acknowledge patient perspectives and ensure that clinical practices remain patient-focused. This study highlights important considerations for integrating PGx testing into antidepressant pharmacotherapy and emphasizes the need for future research to address and mitigate the perceived barriers of young adults.

PMID:39830342 | PMC:PMC11739104 | DOI:10.3389/fphar.2024.1526101

Clin Pharmacol Ther. 2025 Jan 20. doi: 10.1002/cpt.3557. Online ahead of print.

ABSTRACT

Tuberculosis (TB) is a major health burden in Africa. Although TB is treatable, anti-TB drugs are associated with adverse drug reactions (ADRs), which are partly attributed to pharmacogenetic variation. The distribution of star alleles (haplotypes) influencing anti-TB drug metabolism is unknown in many African populations. This presents challenges in implementing genotype-guided therapy in Africa to decrease the occurrence of ADRs and enhance the efficacy of anti-TB drugs. In this study, we used StellarPGx to call variants and star alleles in NAT1, NAT2, GSTM1, GSTT1, GSTP1, and CYP2E1, from 1079 high-depth African whole genomes. We present the distribution of common, rare, and potential novel star alleles across various Sub-Saharan African (SSA) populations, in comparison with other global populations. NAT1*10 (53.6%), GSTT1*0 (65%), GSTM1*0 (48%), and NAT2*5 (17.5%) were among the predominant functionally relevant star alleles. Additionally, we predicted varying phenotype distributions for NAT1 and NAT2 (acetylation) and the glutathione-S-transferase (GST) enzymes (detoxification activity) between SSA and other global populations. Forty-seven potentially novel haplotypes were identified computationally across the genes. This study provides insight into the distribution of key variants and star alleles potentially relevant to anti-TB drug metabolism and other drugs prescribed across various African populations. The high number of potentially novel star alleles exemplifies the need for pharmacogenomics studies in the African context. Overall, our study provides a foundation for functional pharmacogenetic studies and potential implementation of pharmacogenetic testing in Africa to reduce the risk of ADRs related to treatment of TB and other diseases.

PMID:39829327 | DOI:10.1002/cpt.3557

Pharmacogenomics. 2025 Jan 19:1-5. doi: 10.1080/14622416.2025.2454217. Online ahead of print.

ABSTRACT

BACKGROUND: Macrolides are widely used antibiotics, but adverse drug reactions (ADRs), particularly in genetically predisposed individuals, can compromise their safety. This study examines the impact of pharmacogenetic markers on macrolide safety in participants with bacterial complications of influenza.

OBJECTIVE: To evaluate how polymorphisms in genes encoding transporter proteins (ABCB1) and enzymes (CYP3A4, CYP3A5) influence ADR risk during macrolide therapy.

METHODS: A prospective study included 100 participants with lower respiratory tract bacterial complications of influenza treated with azithromycin or erythromycin for five days. Genotyping targeted ABCB1 (3435C>T), CYP3A4 (C>T intron 6), and CYP3A5 (6986A>G) polymorphisms. ADRs were monitored daily and correlated with genetic markers.

RESULTS: The ABCB1 (3435C>T) polymorphism was associated with higher rates of abdominal pain and diarrhea in CT and TT genotypes (OR = 2.12, p = 0.043). The CYP3A4 (C>T intron 6) polymorphism increased ADR risk in erythromycin-treated participants (OR = 24.0, p = 0.0339). No significant effects were observed for CYP3A5 (6986A>G).

CONCLUSION: Genetic polymorphisms in ABCB1 and CYP3A4 genes predict macrolide-related ADRs. Pharmacogenetic screening could improve macrolide safety, particularly for genetically susceptible individuals.

PMID:39829075 | DOI:10.1080/14622416.2025.2454217

Headache. 2025 Jan 17. doi: 10.1111/head.14903. Online ahead of print.

ABSTRACT

Antibodies targeting either the calcitonin gene-related peptide (CGRP), such as galcanezumab, fremanezumab, and eptinezumab, or the receptor (erenumab) have been approved for the prevention of episodic and chronic migraine. Although widely used and generally effective, a proportion of patients discontinue treatment due to lack of efficacy. In both randomized controlled trials and observational studies, all anti-CGRP monoclonal antibodies (mAbs) have consistently demonstrated comparable efficacy and tolerability, suggesting a pharmacological class effect. However, differences in therapeutic targets, structure, and pharmacokinetic characteristics may influence their efficacy and safety differently. Therefore, in patients not achieving a clinically meaningful response with one anti-CGRP antibody, switching to a different antibody may be a viable option. This review examines the pharmacological characteristics and distinctions among anti-CGRP mAbs, highlighting their mechanisms of action and pharmacokinetic profiles, along with the clinical observational data of switching. Finally, we summarize suggestions from international guidelines.

PMID:39825578 | DOI:10.1111/head.14903

Genome Med. 2025 Jan 17;17(1):5. doi: 10.1186/s13073-025-01432-w.

ABSTRACT

BACKGROUND: Despite extensive analysis, the dynamic changes in prostate epithelial cell states during tissue homeostasis as well as tumor initiation and progression have been poorly characterized. However, recent advances in single-cell RNA-sequencing (scRNA-seq) technology have greatly facilitated studies of cell states and plasticity in tissue maintenance and cancer, including in the prostate.

METHODS: We have performed meta-analyses of new and previously published scRNA-seq datasets for mouse and human prostate tissues to identify and compare cell populations across datasets in a uniform manner. Using random matrix theory to denoise datasets, we have established reference cell type classifications for the normal mouse and human prostate and have used optimal transport to compare the cross-species transcriptomic similarities of epithelial cell populations. In addition, we have integrated analyses of single-cell transcriptomic states with copy number variants to elucidate transcriptional programs in epithelial cells during human prostate cancer progression.

RESULTS: Our analyses demonstrate transcriptomic similarities between epithelial cell states in the normal prostate, in the regressed prostate after androgen-deprivation, and in primary prostate tumors. During regression in the mouse prostate, all epithelial cells shift their expression profiles toward a proximal periurethral (PrU) state, demonstrating an androgen-dependent plasticity that is restored to normal during androgen restoration and gland regeneration. In the human prostate, we find substantial rewiring of transcriptional programs across epithelial cell types in benign prostate hyperplasia and treatment-naïve prostate cancer. Notably, we detect copy number variants predominantly within luminal acinar cells in prostate tumors, suggesting a bias in their cell type of origin, as well as a larger field of transcriptomic alterations in non-tumor cells. Finally, we observe that luminal acinar tumor cells in treatment-naïve prostate cancer display heterogeneous androgen receptor (AR) signaling activity, including a split between AR-positive and AR-low profiles with similarity to PrU-like states.

CONCLUSIONS: Taken together, our analyses of cellular heterogeneity and plasticity provide important translational insights into the origin and treatment response of prostate cancer. In particular, the identification of AR-low tumor populations suggests that castration-resistance and predisposition to neuroendocrine differentiation may be pre-existing properties in treatment-naïve primary tumors that are selected for by androgen-deprivation therapies.

PMID:39825401 | DOI:10.1186/s13073-025-01432-w

Pharmacogenomics. 2025 Jan 17:1-9. doi: 10.1080/14622416.2025.2452834. Online ahead of print.

ABSTRACT

AIMS: To ascertain and describe pharmacogenomic concepts included in the intended curriculum of accredited Australian medical schools.

METHODS: Content analysis of curriculum learning objectives of Australian medical schools was conducted, focusing on keywords and phrases pertaining to pharmacogenomic education. Learning objectives related to pharmacogenomics were categorized using (1) undergraduate medical genomic competencies per the Association of Professors in Human and Medical Genetics (2) Bloom's Taxonomy for cognitive and knowledge dimensions and (3) knowledge translation (enabling science, translation science and clinical implementation).

RESULTS: The curricula of 19 accredited medical schools in Australia were analyzed. Two-thirds (68%) contained genomic/pharmacogenomic education. Eight schools had content relating to undergraduate medical genomic competencies. Of those which had pharmacogenomic-related learning objectives, the majority (65%) were categorized in Bloom's Taxonomy's lower levels (Remember and Understand) and 15% were deemed to be at the level of 'Clinical Implementation.'

CONCLUSION: The majority of Australian medical schools have incorporated pharmacogenomics in their current curriculum; however, learning objectives addressing application and clinical implementation are required. Doctors have a unique role to play in implementing pharmacogenomics into clinical practice. Comprehensiveness of course curricula across all learning domains would support uptake of pharmacogenomics into routine practice.

PMID:39824782 | DOI:10.1080/14622416.2025.2452834

Am J Hum Genet. 2025 Jan 10:S0002-9297(24)00461-0. doi: 10.1016/j.ajhg.2024.12.019. Online ahead of print.

ABSTRACT

Nutrient-dependent mTORC1 regulation upon amino acid deprivation is mediated by the KICSTOR complex, comprising SZT2, KPTN, ITFG2, and KICS2, recruiting GATOR1 to lysosomes. Previously, pathogenic SZT2 and KPTN variants have been associated with autosomal recessive intellectual disability and epileptic encephalopathy. We identified bi-allelic KICS2 variants in eleven affected individuals presenting with intellectual disability and epilepsy. These variants partly affected KICS2 stability, compromised KICSTOR complex formation, and demonstrated a deleterious impact on nutrient-dependent mTORC1 regulation of 4EBP1 and S6K. Phosphoproteome analyses extended these findings to show that KICS2 variants changed the mTORC1 proteome, affecting proteins that function in translation, splicing, and ciliogenesis. Depletion of Kics2 in zebrafish resulted in ciliary dysfunction consistent with a role of mTORC1 in cilia biology. These in vitro and in vivo functional studies confirmed the pathogenicity of identified KICS2 variants. Our genetic and experimental data provide evidence that variants in KICS2 are a factor involved in intellectual disability due to its dysfunction impacting mTORC1 regulation and cilia biology.

PMID:39824192 | DOI:10.1016/j.ajhg.2024.12.019

Leuk Res. 2025 Jan 7;149:107644. doi: 10.1016/j.leukres.2025.107644. Online ahead of print.

ABSTRACT

Tyrosine kinase inhibitors (TKIs) targeting BCR::ABL1 are highly successful in chronic myeloid leukemia (CML). However, extensive interpatient variability in therapeutic responses and resistance supports the need to find new prognostic biomarkers. We have previously reported that TP53 SNP215 variant affects CML risk and clinical outcome. We aimed to evaluate the role of MDM2 genetic variants in CML susceptibility and treatment response to TKIs. We genotyped five MDM2 promoter variants (del1518, SNP309, SNP285, SNP288 and SNP344) in 135 CML patients and 136 healthy individuals. Our study showed that MDM2 variants alone or in combination had no effect on CML susceptibility. The analysis of MDM2 genotypes in relation to patients' clinical parameters revealed that individuals with SNP309 G/G genotypes were at a significantly increased risk of undergoing molecular response failure (p = 0.044). Improved overall survival was also observed for non-responders with the alternative MDM2 del1518 del allele (p = 0.017) as well as for MDM2 del1518-SNP309 combinations with alternative genotypes (p = 0.014). In addition, combinatorial analysis demonstrated that alternative MDM2 SNP309 and TP53 SNP215 genotypes together are associated with faster achievement of MR2 (p = 0.029) and MMR (p = 0.042) in non-responders, suggesting a relationship with a favorable outcome. Overall, our study highlights the influence of MDM2 variants on clinical outcome, supporting that specific genotypes, alone or in combination, underlie the treatment-responsive phenotype.

PMID:39823766 | DOI:10.1016/j.leukres.2025.107644

Genet Med Open. 2024 Mar 20;2:101840. doi: 10.1016/j.gimo.2024.101840. eCollection 2024.

ABSTRACT

The number of human disease genes has dramatically increased over the past decade, largely fueled by ongoing advances in sequencing technologies. In parallel, the number of available clinical genetic tests has also increased, including the utilization of exome sequencing for undiagnosed diseases. Although most clinical sequencing tests have been centered on enrichment-based multigene panels and exome sequencing, the continued improvements in performance and throughput of genome sequencing suggest that this technology is emerging as a potential platform for routine clinical genetic testing. A notable advantage is a single workflow with the opportunity to reflexively interrogate content as clinically indicated; however, challenges with implementing routine clinical genome sequencing still remain. This review is centered on evaluating the applications of genome sequencing as a single platform for clinical constitutional genetic testing, including its potential utility for diagnostic testing, carrier screening, cytogenomic molecular karyotyping, prenatal testing, mitochondrial genome interrogation, and pharmacogenomic and polygenic risk score testing.

PMID:39822265 | PMC:PMC11736070 | DOI:10.1016/j.gimo.2024.101840

Clin Transl Sci. 2025 Jan;18(1):e70131. doi: 10.1111/cts.70131.

ABSTRACT

In neurovascular settings, including treatment and prevention of ischemic stroke and prevention of thromboembolic complications after percutaneous neurointerventional procedures, dual antiplatelet therapy with a P2Y12 inhibitor and aspirin is the standard of care. Clopidogrel remains the most commonly prescribed P2Y12 inhibitor for neurovascular indications. However, patients carrying CYP2C19 no-function alleles have diminished capacity for inhibition of platelet reactivity due to reduced formation of clopidogrel's active metabolite. In patients with cardiovascular disease undergoing a percutaneous coronary intervention, CYP2C19 no-function allele carriers treated with clopidogrel experience a higher risk of major adverse cardiovascular outcomes, and multiple large prospective outcomes studies have shown an improvement in clinical outcomes when antiplatelet therapy selection was guided by CYP2C19 genotype. Similarly, accumulating evidence has associated CYP2C19 no-function alleles with poor clinical outcomes in clopidogrel-treated patients in neurovascular settings. However, the utility of implementing a genotype-guided antiplatelet therapy selection strategy in the setting of neurovascular disease and the clinical outcomes evidence in neurointerventional procedures remains unclear. In this review, we will (1) summarize existing evidence and guideline recommendations related to CYP2C19 genotype-guided antiplatelet therapy in the setting of neurovascular disease, (2) evaluate and synthesize the existing evidence on the relationship of clinical outcomes to CYP2C19 genotype and clopidogrel treatment in patients undergoing a percutaneous neurointerventional procedure, and (3) identify knowledge gaps and discuss future research directions.

PMID:39822142 | DOI:10.1111/cts.70131

Mayo Clin Proc. 2025 Jan 14:S0025-6196(24)00546-9. doi: 10.1016/j.mayocp.2024.10.016. Online ahead of print.

NO ABSTRACT

PMID:39818680 | DOI:10.1016/j.mayocp.2024.10.016

Biometrics. 2025 Jan 7;81(1):ujae169. doi: 10.1093/biomtc/ujae169.

ABSTRACT

Pharmacogenomics stands as a pivotal driver toward personalized medicine, aiming to optimize drug efficacy while minimizing adverse effects by uncovering the impact of genetic variations on inter-individual outcome variability. Despite its promise, the intricate landscape of drug metabolism introduces complexity, where the correlation between drug response and genes can be shaped by numerous nongenetic factors, often exhibiting heterogeneity across diverse subpopulations. This challenge is particularly pronounced in datasets such as the International Warfarin Pharmacogenetic Consortium (IWPC), which encompasses diverse patient information from multiple nations. To capture the between-patient heterogeneity in dosing requirement, we formulate a novel change surface model as a model-based approach for multiple subgroup identification in complex datasets. A key feature of our approach is its ability to accommodate nonlinear subgroup divisions, providing a clearer understanding of dynamic drug-gene associations. Furthermore, our model effectively handles high-dimensional data through a doubly penalized approach, ensuring both interpretability and adaptability. We propose an iterative 2-stage method that combines a change point detection technique in the first stage with a smoothed local adaptive majorize-minimization algorithm for surface regression in the second stage. Performance of the proposed methods is evaluated through extensive numerical studies. Application of our method to the IWPC dataset leads to significant new findings, where 3 subgroups subject to different pharmacogenomic relationships are identified, contributing valuable insights into the complex dynamics of drug-gene associations in patients.

PMID:39817854 | DOI:10.1093/biomtc/ujae169

J Clin Endocrinol Metab. 2025 Jan 16:dgaf025. doi: 10.1210/clinem/dgaf025. Online ahead of print.

ABSTRACT

CONTEXT: The response to treatment with vitamin D varies between patients.

OBJECTIVE: To identify genetic variants associated with the biochemical response to vitamin D3 supplementation.

DESIGN: Randomized placebo-controlled trial conducted between 2017 and 2019.

SETTING: The trial was nested in an ongoing community-based cohort study, the Multi-Ethnic Study of Atherosclerosis (MESA).

INTERVENTION: 2,000 International Units of vitamin D3 or placebo daily for 16 weeks.

PARTICIPANTS: The analytic sample included 427 participants assigned to vitamin D3 (mean age 73 y, 54% females) and was 36% White, 33% Black, 18% Hispanic, and 14% Chinese.

MAIN OUTCOME MEASURES: The biochemical response to vitamin D3 included changes in serum concentrations of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], parathyroid hormone (PTH), and 25-hydroxyvitamin D3 [25(OH)D3].

RESULTS: In genome-wide analyses, SNPs in 8 regions of the genome had significant association (p < 5E-08) with one of the traits (2 with change in 1,25(OH)2D3, 1 with change in PTH, and 5 with change in 25(OH)D3). rs16867276 within an intergenic region on 2q31 was associated with change in serum 1,25(OH)2D3 (+8.37 pg/mL difference per effect allele; p = 4.93E-08) and was the only locus that achieved genome-wide significance in transethnic meta-analysis. rs114044709 adjacent to FAM20A, which encodes a protein required for biomineralization, was associated with change in PTH among Black participants (+20.32 pg/mL difference per effect allele; p = 1.34E-08). In candidate analyses, SNPs within SULT2A1 and CYP24A1 had significant association (p < 0.05 ÷ 36 = 0.0014) with the changes in 1,25(OH)2D3 and PTH, respectively.

CONCLUSIONS: Our results reveal potential new pathways of vitamin D regulation that require replication in other vitamin D trials.

PMID:39815761 | DOI:10.1210/clinem/dgaf025

Drug Metab Rev. 2025 Jan 20:1-24. doi: 10.1080/03602532.2025.2453521. Online ahead of print.

ABSTRACT

Idiosyncratic drug reactions (IDRs) pose severe threats to patient health. Unlike conventionally dose-dependent side effects, they are unpredictable and more frequently manifest as life-threatening conditions, such as severe cutaneous adverse reactions (SCARs) and drug-induced liver injury (DILI). Some HLA alleles, such as HLA-B*57:01, HLA-B*15:02, and HLA-B*58:01, are known risk factors for adverse reactions induced by multiple drugs. However, the structural basis underlying most HLA-associated adverse events remains poorly understood. This review summarizes the application of molecular docking to reveal the mechanisms of IDR-related HLA associations, covering studies using this technique to examine drug-HLA binding pockets and identify key binding residues. We provide a comprehensive overview of risk HLA alleles associated with IDRs, followed by a discussion of the utility and limitations of commonly used molecular docking tools in simulating complex molecular interactions within the HLA binding pocket. Through examples, including the binding of abacavir and flucloxacillin to HLA-B*57:01, carbamazepine to HLA-B*15:02, and allopurinol to HLA-B*58:01, we demonstrate how docking analyses can provide insights into the drug and HLA allele-specificity of adverse events. Furthermore, the use of molecular docking to screen drugs with unknown IDR liability is examined, targeting either multiple HLA variants or a single specific variant. Despite multiple challenges, molecular docking presents a promising toolkit for investigating drug-HLA interactions and understanding IDR mechanisms, with significant implications for preemptive HLA typing and safer drug development.

PMID:39811883 | DOI:10.1080/03602532.2025.2453521

Drug Metab Pers Ther. 2025 Jan 2;39(4):163-165. doi: 10.1515/dmpt-2024-0091. eCollection 2024 Dec 1.

NO ABSTRACT

PMID:39814711 | DOI:10.1515/dmpt-2024-0091

Platelets. 2025 Dec;36(1):2449344. doi: 10.1080/09537104.2024.2449344. Epub 2025 Jan 15.

ABSTRACT

Platelet-like particles (PLPs), derived from megakaryocytic cell lines MEG-01 and K-562, are widely used as a surrogate to study platelet formation and function. We demonstrate by RNA-Seq that PLPs are transcriptionally distinct from platelets. Expression of key genes in signaling pathways promoting platelet activation/aggregation, such as the PI3K/AKT, protein kinase A, phospholipase C, and α-adrenergic and GP6 receptor pathways, was missing or under-expressed in PLPs. Functionally, PLPs do not aggregate following epinephrine, collagen, or ADP stimulation. While PLPs aggregated in response to thrombin, they did not display enhanced expression of surface markers P-selectin and activated α2bβ3, in contrast to platelets. We have previously demonstrated that platelets physically couple to MDA-PCa-2b and RC77T/E prostate cancer (PCa) cells via specific ligand-receptor interactions, leading to platelet-stimulated cell invasiveness and apoptotic resistance, and reciprocal cell-induced platelet aggregation. In contrast, PLP interactions with PCa cells inhibited both cell invasion and apoptotic resistance while failing to promote PLP aggregation. Moreover, PLPs reduced platelet-PCa cell interactions and antagonized platelet-stimulated oncogenic effects in PCa cells. RNA-Seq analysis identified candidate ligand-transmembrane protein combinations involved in anti-tumorigenic signaling of PLPs to PCa cells. Antibody neutralization of the TIMP3-MMP15 and VEGFB-FGFR1 signaling axes reversed PLP-mediated anti-invasion and apoptotic sensitization, respectively. In summary, PLPs lack many transcriptomic, molecular and functional features of platelets and possess novel anti-tumorigenic properties. These findings indicate that PLPs may have a potential therapeutic role in targeting and disrupting the oncogenic signaling between platelets and cancer cells, offering a new avenue for anti-cancer strategies.

PMID:39812346 | DOI:10.1080/09537104.2024.2449344

Heliyon. 2024 Dec 18;11(1):e41108. doi: 10.1016/j.heliyon.2024.e41108. eCollection 2025 Jan 15.

ABSTRACT

INTRODUCTION: Severe cutaneous adverse reactions (SCARs) are life-threatening and often linked to antiepileptic drugs (AEDs). Common types of SCARs include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS). Immune-mediated mechanisms involving human leukocyte antigen (HLA) alleles have been implicated in the pathogenesis of this reaction. This study examines the association between specific HLA alleles (HLA-A, -B, and -DRB1) and AED-induced SCARs in the Iraqi population.

METHODOLOGY: A total of 50 patients diagnosed with SCARs and 90 tolerant controls were recruited from Dr. Saad Al-Wattari Hospital for Neurological Sciences and Baghdad Hospital - Medical City. HLA genotyping was performed using PCR-SSO method from peripheral blood samples. Statistical comparisons were made using the t-test or chi-square test, while univariate logistic regression with Bonferroni's correction (p < 0.05) were used to assess associations between HLA alleles and SCARs.

RESULTS: Among the patients, SJS was the most prevalent type of SCARs observed. Analysis of HLA allele frequencies revealed significant associations between specific alleles. HLA-A∗02:01 was found to be significantly associated with a lower risk of AED-induced SJS (OR = 0.36; 95 % CI: 0.13-0.97), while HLA-A∗24:02 and HLA-B∗15:02 were associated with an increased risk of AED-induced SJS (OR = 3.60; 95 % CI: 1.21-10.72 and OR = 4.41; 95 % CI: 1.18-16.47, respectively). For AED-induced TEN, HLA-A∗01:02, HLA-B∗15:02, and HLA-B∗52:01 showed significant associations (OR = 6.92; 95 % CI: 1.39-34.37 and OR = 6.55; 95 % CI: 1.62-26.52, respectively), with HLA-DRB1∗03:01 being highly significant (OR = 5.09; 95 % CI: 1.72-15.00). Additionally, HLA-B∗40:02 was strongly associated with AED-induced DRESS (OR = 29.33; 95 % CI: 3.50-245.32).

CONCLUSION: This study identifies key HLA alleles associated with AED-induced SCARs in the Iraqi population. These findings could facilitate personalized medicine approaches, aiding in better prediction and prevention of SCARs in AED therapy.

PMID:39811327 | PMC:PMC11732454 | DOI:10.1016/j.heliyon.2024.e41108

World Psychiatry. 2025 Feb;24(1):141-142. doi: 10.1002/wps.21289.

NO ABSTRACT

PMID:39810666 | DOI:10.1002/wps.21289

Anal Methods. 2025 Jan 15. doi: 10.1039/d4ay01941e. Online ahead of print.

ABSTRACT

Saponins are responsible for the clinical effects of Panax notoginseng leaves, which are traditionally produced as the single herb resource of 'Qiye Shenan Pian' in Chinese patent medicine. In this study, the metabolic characteristics of PNLSs were explored in rat feces. PNLSs as well as their metabolites were analyzed by ultra-performance liquid chromatography tandem/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS). Subsequently, seventy-five metabolites were tentatively identified in the control group mainly due to the deglycosylation and dehydration biopathways, but only twenty low yields were determined in the pseudo-germ-free (GF) group. Ginsenoside compound K was the predominant metabolite in the control group. The data presented that gut microbiota played a pivotal role in the metabolic kinetics of PNLSs.

PMID:39810648 | DOI:10.1039/d4ay01941e