Int J Mol Sci. 2025 Feb 19;26(4):1757. doi: 10.3390/ijms26041757.

ABSTRACT

The extracts from fruits of Chaenomeles japonica (Thunb.) Lindl. ex Spach (CJE), Cornus mas L. (CME), and Hippophaё rhamnoides L. (HRE) are known inhibitors of a variety of eukaryotic hydrolases, engaged in the digestion of fats and polysaccharides. However, there are no data on their potential interaction with the bacterial hydrolases participating in the replication of microbial nucleic acids. This analysis predicted the interaction of the most abundant constituents of HRE, CJE, and CME with the bacterial nucleases. The analysis covered the molecular docking of isorhamnetin glycosides, procyanidins C1 and B2, epicatechin, loganic acid, and cornuside with bacterial enzymes (Escherichia coli endonuclease 1, colicin E9, and ribonuclease H; or Staphylococcus aureus thermonuclease and nuclease SbcCD). The suggested complexes have been subjected to molecular mechanics with generalized Born and surface area solvation (MM/GBSA) calculations. The second aim was the in vitro evaluation of the influence of the CJE, HRE, and CME on the metabolic activity of bacterial biofilm of selected microbial strains, as well as fibroblasts (L929) and adenocarcinoma intestinal cells (Caco-2) toxicity. Among all extracts, CME showed the most relevant effect on the survival of planktonic cells and biofilm of E. coli and Pseudomonas aeruginosa. As a result of in silico studies, most virtual hits were predicted to inhibit the proteins under investigation, except for procyanidin C1. Further research on the direct interaction of phytochemicals and selected enzymes in vitro is required and challenged.

PMID:40004218 | DOI:10.3390/ijms26041757

Int J Mol Sci. 2025 Feb 13;26(4):1571. doi: 10.3390/ijms26041571.

ABSTRACT

(6S,9R)-vomifoliol (VO) is a natural norisoprenoid of the megastigmane type derived from Gaultheria procumbens, an aromatic, evergreen shrub whose leaves, fruits, and aerial parts are used in traditional phytotherapy to treat oxidative stress and inflammation-related disorders. The plant is known as a rich source of essential oil and polyphenols. However, the levels of other constituents of G. procumbens, including VO, have yet to be explored. There is also a knowledge gap in the pharmacological potential of VO in the context of inflammation. Therefore, the present study aimed to investigate the accumulation of VO in leaves, stems, and fruits of G. procumbens and to determine its antioxidant and anti-inflammatory effects in non-cellular in vitro and cell-based models of human immune cells ex vivo. The GC-FID-MS (gas chromatography coupled with flame ionisation detector and mass spectrometer) analysis revealed the leaves as the richest source of VO (0.36 mg/g dw of the plant material) compared to other G. procumbens organs. In non-cellular activity tests, VO showed comparable to positive control anti-inflammatory activity against lipoxygenase, with significantly weaker impact on hyaluronidase and cyclooxygenase-2, and no effect on cyclooxygenase-1 isozyme. VO at 5-75 μM revealed a significant and dose-dependent ability to reduce the reactive oxygen species (ROS) level, downregulate the release of pro-inflammatory cytokines [tumour necrosis factor-α (TNF-α), interleukin-8 (IL-8), IL-6, and IL-1β] and tissue-remodelling enzymes (elastase-2, metalloproteinase-9), and up-regulate the secretion of anti-inflammatory cytokine IL-10 in bacterial lipopolysaccharide (LPS)- and N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP)-stimulated human neutrophils and peripheral blood mononuclear cells (PBMCs) ex vivo. Furthermore, a significant reduction in IL-6, lipoxygenase (LOX), nuclear factor κ-light-chain-enhancer of activated B cells 1 (NF-κB1), and NF-κB2 gene expression in LPS-stimulated peripheral blood lymphocytes was demonstrated by real-time PCR. The cellular safety of VO at 5-75 μM was confirmed by flow cytometry, with the viability of neutrophils and PBMCs after incubation with VO at 93.8-98.4%. The results encourage further studies of VO as a promising non-cytotoxic natural anti-inflammatory agent and support the use of leaves of G. procumbens in the adjuvant treatment of oxidative stress and inflammation-related diseases of affluence.

PMID:40004039 | DOI:10.3390/ijms26041571

Life (Basel). 2025 Jan 22;15(2):144. doi: 10.3390/life15020144.

ABSTRACT

Endometriosis afflicts 10% of women in their reproductive years and nearly half of women with infertility, and its etiology is not yet clear. Pharmacological therapy is generally based on progestins like progestogen. This drug binds to progesterone receptors with many known side effects. Here, we describe the case of a 33-year-old woman surgically treated for endometriosis who continued with drug therapy based on estradiol valerate and dienogest. Approximately 21 months after treatment, she reported ocular symptoms with vision alteration, diplopia, and metamorphopsia related to central serous chorioretinopathy (CSC). After the discontinuation of combined progestin-based treatment, the CSC fully subsided. Semeiological, clinical, and laboratory approaches were adopted, and urinary steroids were measured. A slight increase in prolactinemia in the absence of macro-prolactinemia was reported. The steroidal profile appeared without abnormalities, although a slight alteration of estrogen balance was noted. Considering the pharmacodynamics of dienogest versus selective progesterone receptor modulators, it can be assumed that patients' clinical events are related to specific site response to steroids that bind the progesterone receptor. Dienogest may have induced the CSC as a not yet characterized side effect of the drug. Undoubtedly, further specific studies are needed concerning the metabolic and pharmacodynamic aspects that cannot be exhaustively covered here.

PMID:40003553 | DOI:10.3390/life15020144

Biomedicines. 2025 Feb 12;13(2):447. doi: 10.3390/biomedicines13020447.

ABSTRACT

Type 2 diabetes (T2D) is the fastest-growing non-communicable disease worldwide, accounting for around 90% of all diabetes cases and imposing a significant health burden globally. Due to its phenotypic heterogeneity and composite genetic underpinnings, T2D requires a precision medicine approach personalized to individual molecular profiles, thereby shifting away from the traditional "one-size-fits-all" medical methods. This review advocates for a thorough pharmacomultiomics approach to enhance precision medicine for T2D. It emphasizes personalized treatment strategies that enhance treatment efficacy while minimizing adverse effects by integrating data from genomics, proteomics, metabolomics, transcriptomics, microbiomics, and epigenomics. We summarize key findings on candidate genes impacting diabetic medication responses and explore the potential of pharmacometabolomics in predicting drug efficacy. The role of pharmacoproteomics in prognosis and discovering new therapeutic targets is discussed, along with transcriptomics' contribution to understanding T2D pathophysiology. Additionally, pharmacomicrobiomics is explored to understand gut microbiota interactions with antidiabetic drugs. Emerging evidence on utilizing epigenomic profiles in improving drug efficacy and personalized treatment is also reviewed, illustrating their implications in personalized medicine. In this paper, we discuss the integration of these layers of omics data, examining recently developed paradigms that leverage complex data to deepen our understanding of diabetes. Such integrative approaches advance precision medicine strategies to tackle the disease by better understanding its complex biology.

PMID:40002860 | DOI:10.3390/biomedicines13020447

Biomedicines. 2025 Jan 24;13(2):291. doi: 10.3390/biomedicines13020291.

ABSTRACT

Background: Resistin (RETN), an inflammatory cytokine exhibiting multifaceted roles in cancer progression, has emerged as a plausible mediator between inflammation and oncogenesis. Prior research from our group has highlighted the pivotal role of resistin in carcinogenesis and its impact on drug responsiveness. The present study delves into the relationship between resistin expression and genetic polymorphisms with cancer risk and clinical outcomes among lung cancer patients undergoing platinum-based chemotherapy. Methods: Immunohistochemical analysis was conducted to assess resistin expression levels in 104 tumor tissues derived from lung adenocarcinoma patients. Additionally, 498 lung cancer patients and 213 healthy controls were recruited for this study, with 467 patients undergoing at least two cycles of platinum-based chemotherapy. Unconditional logistical regression analysis was employed to evaluate the associations between RETN polymorphisms and lung cancer risk, as well as clinical outcomes. Genotyping of RETN polymorphisms (rs1862513 and rs3745367) was performed using the Sequenom MassARRAY System. Results: The findings revealed a positive correlation between resistin expression in tumor tissues and metastasis (particularly distant metastasis) and overall survival in lung adenocarcinoma. However, RETN polymorphisms were not significantly associated with overall survival in lung cancer patients. No substantial association was observed between RETN polymorphisms and lung cancer risk, chemotherapy response, or toxicities, except for rs1862513, which showed a link with severe gastrointestinal toxicity. Meta-analysis results further confirmed the absence of a significant association between RETN polymorphisms and cancer risk. Conclusions: Despite the pivotal role of resistin in carcinogenesis, only the RETN rs1862513 polymorphism emerges as a potential biomarker for gastrointestinal toxicity in lung cancer patients undergoing platinum-based chemotherapy. However, these findings necessitate validation through well-designed studies with larger sample sizes.

PMID:40002704 | DOI:10.3390/biomedicines13020291

Diagnostics (Basel). 2025 Feb 7;15(4):404. doi: 10.3390/diagnostics15040404.

ABSTRACT

Background/Objectives: Lipoprotein (a) [Lp(a)] plays a significant role in atherosclerosis and cardiovascular disease (CVD). Genetic regulation of Lp(a) involves variations in the apo(a) LPA gene, as specific polymorphisms like rs10455872 and rs3798220, both linked to higher Lp(a) levels and CVD. CVD remains the leading global cause of death, with high Lp(a) levels increasingly recognized as a significant factor in younger patients with no other CVD risk factors. We aimed to evaluate the association of LPA genetic variations with Lp(a) levels and its effect on cardiovascular risk as there are existing inconsistent findings. Methods: This case-control study included 251 subjects with a median age of 52 years (interquartile range, IQR = 17) and elevated Lp(a) levels. Cases were subjects who experienced early cardiovascular incidents (women < 65, men < 55 years old), and the control group included subjects without such history. Genotyping of LPA gene polymorphisms (rs10455872 and rs3798220) was performed, and demographic data with Lp(a) levels were collected. To evaluate the association between the LPA genotypes and the risk of cardiovascular incidents (CVI), several logistic regression models were performed. The cut-off points for Lp(a) levels were determined using diagnostic test accuracy measures. Results: The rs3798220-C allele was associated with higher Lp(a) levels (288 ± 166 nmol/L in cases vs. 189 ± 102 nmol/L in controls, p < 0.001) and myocardial infarction (53% in cases vs. 36% in controls, p = 0.036). Among cases, 28.9% carried the rs3798220-C allele, compared to 18.7% in controls. The rs10455872-G allele was slightly more prevalent in controls (34.15% vs. 29.69%) but without further significant associations. In this study, the cut-off Lp(a) value of 151 nmol/L, for patients with a positive family history of early CVD, is associated with a higher chance of developing CVI. Conclusions: This study demonstrates an association between the LPA rs3798220-C allele and higher Lp(a) levels, as well as an increased risk of early onset myocardial infarction. However, the obtained association should further be evaluated at a much larger scale.

PMID:40002555 | DOI:10.3390/diagnostics15040404

Antibiotics (Basel). 2025 Feb 16;14(2):204. doi: 10.3390/antibiotics14020204.

ABSTRACT

Background/Objectives: Studies show that SNPs in ABCB1 rs2032582 and SLCO1B1 rs4149015 affect the PK profile of moxifloxacin, a key drug for MDR-TB. This study aimed to assess the genotype frequencies of ABCB1 rs2032582 and SLCO1B1 rs4149015; describe moxifloxacin AUC0-24 and Cmax; and evaluate the association between genotype variations and moxifloxacin AUC0-24 and Cmax, corrected for the effect of other determinants in MDR-TB patients in Indonesia. Methods: The genotypes were identified using DNA sequencing. Plasma samples for PK analysis were collected at either two or four timepoints post-dose, at steady state. AUC0-24 values were assessed with a limited sampling formula. A multivariate linear regression analysis identified the determinants for moxifloxacin AUC0-24 and Cmax. Results: We recruited 204 MDR-TB patients for PG analysis, with 80 providing PK samples. The majority of the ABCB1 and SLCO1B1 genotypes were wildtype (GG), 41.7% and 93.6%, respectively. The geometric mean AUC0-24 for moxifloxacin was 78.6 mg·h/L and that for Cmax was 6.1 mg/L. No statistically significant difference in exposure to moxifloxacin could be shown between the genotypes. Sex, age, and dose in mg/kg/body weight were significant determinants of the AUC0-24 of moxifloxacin. Conclusions: The major genotype of ABCB1 rs2032582 and SLCO1B1 rs4149015 was wildtype, and the exposure to moxifloxacin was high but not related to the studied genotype in an Indonesian population.

PMID:40001447 | DOI:10.3390/antibiotics14020204

Br J Clin Pharmacol. 2025 Feb 25. doi: 10.1002/bcp.70026. Online ahead of print.

ABSTRACT

AIMS: The influence of CYP2C19 polymorphisms on voriconazole plasma concentrations is recognized, but its extent, other contributing factors and risks for adverse reactions remain under-explored.

METHODS: This study focused on Japanese paediatric patients recruited between 2020 and 2022 treated with voriconazole. We specifically investigated the occurrence of cholestasis and thrombocytopenia as adverse reactions of voriconazole. Voriconazole plasma levels were modelled in a previous study using a population pharmacokinetics approach. Missing values were estimated with a Bayesian method in Phoenix NLME. We analysed CYP2C19*2, CYP2C19*3 and CYP2C19*17. Clinical and laboratory data were collected before and after voriconazole treatment.

RESULTS: Among the 60 patients (mean age: 6.5 years; 53.3% male), 38 had haematological malignancies, 18 inborn errors of immunity, 2 solid tumours and 2 other diseases. Adverse reactions occurred in 12 patients. The voriconazole plasma concentrations were significantly higher in those experiencing these adverse reactions (mean normalized concentrations: 0.66 in cases vs. -0.16 in controls, P = .025), with a trend towards higher concentrations in carriers of the CYP2C19*2 or *3 alleles (mean normalized concentrations: 0.98 in carrier cases vs. 0.016 in noncarrier cases, P = .14). A predictive model for voriconazole concentrations, incorporating carriership of CYP2C19*2 or *3, C-reactive protein levels, and platelet counts, showed a summed variance explained of 23.6% with the variance attributable to CYP2C19*2 or *3 carrier status alone was 2.6%. Including carrier status improved the area under the receiver operating characteristic curve for predicting adverse reactions to 0.70.

CONCLUSIONS: Our findings underscore the role of the CYP2C19 polymorphism in voriconazole-induced thrombocytopenia and cholestasis.

PMID:40001258 | DOI:10.1002/bcp.70026

Reprod Biol Endocrinol. 2025 Feb 25;23(Suppl 1):29. doi: 10.1186/s12958-025-01359-2.

ABSTRACT

Luteinizing hormone (LH) is fundamental to support development and reproduction. It acts through a receptor expressed in the gonads, modulating mitogenic, anti-apoptotic, and steroidogenic signals. LH is also marketed as a drug for controlled ovarian stimulation (COS), where it is administered to women to support the action of follicle-stimulating hormone and can lead to specific responses, depending on the individual genetic background. These concepts underline the relevance of a pharmacogenetic approach to COS, in the attempt to optimize clinical outcomes and avoid adverse events. However, knowledge is currently limited by the paucity of clinical studies. This review aims to provide a comprehensive overview of LH and its receptor activity, starting from the description of their molecular pathways from in vitro studies. Data on LH action from in vivo studies were described, as well as the impact of LH and LH/choriogonadotropin (hCG) receptor genetic variants on folliculogenesis and its association with infertility or polycystic ovarian syndrome. Finally, evidence from clinical studies evaluating genetic polymorphisms in the context of assisted reproductive technology treatments and its implications for a pharmacogenomic approach were discussed.

PMID:40001128 | DOI:10.1186/s12958-025-01359-2

NPJ Precis Oncol. 2025 Feb 25;9(1):53. doi: 10.1038/s41698-025-00837-5.

ABSTRACT

Preclinical models of breast cancer that better predict patient-specific drug responses are critical for expanding the clinical utility of targeted therapies, including for inhibitors of poly(ADP-ribose) polymerase (PARP). Reprogramming primary cancer cells into human induced pluripotent stem cells (hiPSCs) recently emerged as a powerful tool to model drug response phenotypes, but its use to date has been limited to hematopoietic malignancies. We designed an optimized reprogramming methodology to generate breast cancer-derived hiPSCs (BC-hiPSCs) from nine patients representing all major subtypes of breast cancer. BC-hiPSCs retain patient-specific oncogenic variants, including variants unique to individual tumor subclones. Additionally, we developed a protocol to differentiate BC-hiPSCs into mammary epithelial cells and mammary-like organoids for in vitro disease modeling, including drug response phenotyping. Using these tools, we demonstrated that BC-hiPSCs can be used to screen for differential sensitivity to PARP inhibitors and mechanistically investigated the causal genetic variant driving drug sensitivity in one patient.

PMID:40000798 | DOI:10.1038/s41698-025-00837-5

Pharmacogenomics. 2025 Feb 25:1-18. doi: 10.1080/14622416.2025.2470605. Online ahead of print.

ABSTRACT

AIMS: The present review explores the existing evidence on pharmacogenomic tests for prediction of lithium response in the treatment of bipolar disorder. We focused our research article on reports describing findings from genome-wide association studies, polygenic risk scores, and gene expression analyses associated with lithium response.

METHODS: We conducted a non-systematic review of studies from PubMed/Medline by using terms such as "pharmacogenomics," "GWAS," "gene expression," and "lithium response." Inclusion criteria focused on original research involving human subjects and assessing lithium response outcomes as well as in vitro studies. An extensive pearl-growing strategy was employed to further enlarge the scope of the piece by capitalizing on the knowledge of study authors on the subject.

RESULTS: The observed results, albeit promising, remain preliminary in terms of clinical relevance. Machine learning combining genetic and clinical data appears associated with moderate success in predicting lithium responsiveness. Gene expression studies and genome-wide association studies have helped identify possible targets of lithium and have the potential to support target-specific drug research.

CONCLUSIONS: Pharmacogenomics may support further discoveries in precision medicine further enlarging our understanding of the underlying mechanisms of lithium for its efficacy. However, clinical applications currently appear out of reach in the near future.

PMID:39998910 | DOI:10.1080/14622416.2025.2470605

Adv Healthc Mater. 2025 Feb 25:e2404612. doi: 10.1002/adhm.202404612. Online ahead of print.

ABSTRACT

Immunotherapy has fundamentally transformed the clinical treatment landscape for non-small cell lung cancer (NSCLC). While its effectiveness is ultimately limited by patient heterogeneity and immunosuppressive tumor microenvironment. Photodynamic therapy (PDT), as an emerging antitumor immunotherapy, has shown its unique therapeutic advantages. However, previous studies often overlooked the potential toxicity of photosensitizers (PS), making the discovery of safe and effective PS a pressing clinical need. In this study, Aloe Emodin (AE), a medicinal plant natural compound, was loaded with copper ions (Cu), and self-assembled into nanoparticles (NPs) under the modification of PEG2k-DSPE-FA. NPs can target, accumulate, and reside within tumor sites, responsively releasing copper ions and AE, thus dual-functioning by inducing tumor cell death via cuproptosis and enhancing PDT effects. The LLC tumor-bearing mouse model demonstrated that NPs induce the maturation of dendritic cells (DCs) in vivo, promote lymphocyte infiltration, transform "cold tumors" into "hot tumors" and significantly enhance the efficacy of immune checkpoint blockade (ICB). This study provides experimental evidence of AE as a clinically promising PDT agent and offers a novel perspective for the synergistic treatment of clinical NSCLC.

PMID:39998287 | DOI:10.1002/adhm.202404612

Ther Drug Monit. 2025 Feb 25. doi: 10.1097/FTD.0000000000001314. Online ahead of print.

ABSTRACT

Pharmacogenomics (PGx) enhances drug therapy by tailoring treatment to individual genetic profiles, thereby improving safety and efficacy. However, the integration of PGx into clinical practice, particularly in hospitals, faces significant challenges, including limited testing services, variant coverage, and inconsistent guidelines. A recent review, "Implementation and Evaluation Strategies of Pharmacogenetic Testing in Hospital Settings," highlights these challenges and current strategies. Sustaining PGx programs requires ongoing education, support, the integration of advanced technologies, and financial sustainability. Addressing inconsistent insurance coverage, developing standardized methodologies, and implementing clear policies are crucial for widespread adoption, advancement of personalized medicine, and improvement of patient care in hospital settings.

PMID:39996574 | DOI:10.1097/FTD.0000000000001314

Heliyon. 2025 Jan 23;11(3):e42197. doi: 10.1016/j.heliyon.2025.e42197. eCollection 2025 Feb 15.

ABSTRACT

BACKGROUND AND OBJECTIVE: Obesity is intricately linked with metabolic disturbances. The comprehensive exploration of metabolomes is important in unravelling the complexities of obesity development. This study was aimed to discern unique metabolite signatures in obese and lean individuals using liquid chromatography-mass spectrometry quadruple time-of-flight (LC-MS/Q-TOF), with the goal of elucidating their roles in obesity.

METHODS: A total of 160 serum samples (Discovery, n = 60 and Validation, n = 100) of obese and lean individuals with stable Body Mass Index (BMI) values were retrieved from The Malaysian Cohort biobank. Metabolic profiles were obtained using LC-MS/Q-TOF in dual-polarity mode. Metabolites were identified using a molecular feature and chemical formula algorithm, followed by a differential analysis using MetaboAnalyst 5.0. Validation of potential metabolites was conducted by assessing their presence through collision-induced dissociation (CID) using a targeted tandem MS approach.

RESULTS: A total of 85 significantly differentially expressed metabolites (p-value <0.05; -1.5 < FC > 1.5) were identified between the lean and the obese individuals, with the lipid class being the most prominent. A stepwise logistic regression revealed three metabolites associated with increased risk of obesity (14-methylheptadecanoic acid, 4'-apo-beta,psi-caroten-4'al and 6E,9E-octadecadienoic acid), and three with lower risk of obesity (19:0(11Me), 7,8-Dihydro-3b,6a-dihydroxy-alpha-ionol 9-[apiosyl-(1->6)-glucoside] and 4Z-Decenyl acetate). The model exhibited outstanding performance with an AUC value of 0.95. The predictive model underwent evaluation across four machine learning algorithms consistently demonstrated the highest predictive accuracy of 0.821, aligning with the findings from the classical logistic regression statistical model. Notably, the presence of 4'-apo-beta,psi-caroten-4'-al showed a statistically significant difference between the lean and obese individuals among the metabolites included in the model.

CONCLUSIONS: Our findings highlight the significance of lipids in obesity-related metabolic alterations, providing insights into the pathophysiological mechanisms contributing to obesity. This underscores their potential as biomarkers for metabolic dysregulation associated with obesity.

PMID:39995923 | PMC:PMC11848079 | DOI:10.1016/j.heliyon.2025.e42197

Pain Rep. 2025 Feb 21;10(2):e1248. doi: 10.1097/PR9.0000000000001248. eCollection 2025 Apr.

ABSTRACT

INTRODUCTION: The cytochrome P450 enzyme 2D6 (CYP2D6) and the catechol-O-methyltransferase (COMT) enzyme are involved in catecholamine metabolism, potentially influencing pain modulation. Catechol-O-methyltransferase has 3 major haplotypes related to pain sensitivity: low (LPS), average (APS), and high (HPS). However, the reliability of these haplotypes in predicting clinical outcomes is not well investigated. We present a 40-year-old female patient with fibromyalgia. Despite extensive pharmacotherapy with 120 mg/d duloxetine, 150 mg/d pregabalin, 80 mg/d oxycodone, 2 g/d paracetamol, and 1.6 g/d ibuprofen, she suffered from severe pain.

OBJECTIVES: We aim to investigate the patient's susceptibility to analgesic therapy failure (TF) and pain sensitivity with pharmacogenotyping.

METHODS: PGx panel testing, including CYP2D6 and COMT rs4680, was conducted by a commercial provider. Additional genotyping of COMT rs6269, rs4633 and rs4818 was performed applying PCR, restriction fragment length polymorphism assay and sanger sequencing.

RESULTS: The patient was identified as COMT HPS/HPS diplotype carrier and CYP2D6 intermediate metabolizer. CYP2D6 is mainly responsible for the bioactivation of oxycodone into oxymorphone. Reduced CYP2D6 activity may result in a lower oxycodone activation. Considering the coadministration of duloxetine (a moderate CYP2D6 inhibitor), the TF of oxycodone could also be the result of a drug-drug-gene interaction. No other medications were affected by her genetic profile.

CONCLUSION: We hypothesize that the broad TF of pain medications and associated high pain sensitivity could be related to the patient's genetic predisposition in CYP2D6 and COMT, warranting further investigation in a larger patient sample.

PMID:39995492 | PMC:PMC11850035 | DOI:10.1097/PR9.0000000000001248

Front Pharmacol. 2025 Feb 10;16:1552652. doi: 10.3389/fphar.2025.1552652. eCollection 2025.

NO ABSTRACT

PMID:39995412 | PMC:PMC11848066 | DOI:10.3389/fphar.2025.1552652

Pharmacogenomics J. 2025 Feb 25;25(2):4. doi: 10.1038/s41397-025-00363-4.

ABSTRACT

Liver transplantation is the only curative option for patients with advanced stages of liver disease, with tacrolimus used as the immunosuppressive drug of choice. Genetic variability can interfere with drug response, potentially leading to overexposure or underexposure. This study aims to investigate the association of CYP3A4 (rs2740574, rs2242480, rs35599367), CYP3A5 (rs776746, rs10264272), POR (rs1057868) and ABCB1 (rs1128503, rs2229109, rs9282564) gene polymorphisms with infection, acute rejection, and renal failure. The logistic regression model found an influence of CYP3A5 (rs776746) and POR28 (rs1057868) on the development of acute rejection after liver transplantation (p = 0.028). It also found an association between carriers of the variant allele of the POR*28 gene and infection.

PMID:39994182 | DOI:10.1038/s41397-025-00363-4

Cancer Genomics Proteomics. 2025 Mar-Apr;22(2):285-305. doi: 10.21873/cgp.20502.

ABSTRACT

BACKGROUND/AIM: Oncogenic processes are delineated by metabolic dysregulation. Drug likeness is pharmacokinetically tested through the CYP450 enzymatic system, whose genetic aberrations under epigenetic stress could shift male organisms into prostate cancer pathways. Our objective was to predict the susceptibility to prostate neoplasia, focused on benign prostatic hyperplasia (BPH) and prostate cancer (PCa), based on the pharmacoepigenetic and the metabolic profile of Caucasians.

MATERIALS AND METHODS: Two independent cohorts of 47,389 individuals in total were assessed to find risk associations of CYP450 genes with prostatic neoplasia. The metabolic profile of the first cohort was statistically evaluated and frequencies of absorption-distribution-metabolism-excretion-toxicity (ADMET) properties were calculated. Prediction of miRNA pharmacoepigenetic targeting was performed.

RESULTS: We found that prostate cancer and benign prostatic hyperplasia patients of the first cohort shared common cardiometabolic trends. Drug classes C08CA, C09AA, C09CA, C10AA, C10AX of the cardiovascular, and G04CA, G04CB of the genitourinary systems, were associated with increased prostate cancer risk, while C03CA and N06AB of the cardiovascular and nervous systems were associated with low-risk for PCa. CYP3A4*1B was the most related pharmacogenetic polymorphism associated with prostate cancer susceptibility. miRNA-200c-3p and miRNA-27b-3p seem to be associated with CYP3A4 targeting and prostate cancer predisposition. Metabolomic analysis indicated that 11β-OHT, 2β-OHT, 15β-OHT, 2α-OHT and 6β-OHT had a high risk, and 16α-OHT, and 16β-OHT had an intermediate disease-risk.

CONCLUSION: These findings constitute a novel integrated signature for prostate cancer susceptibility. Further studies are required to assess their predictive value more fully.

PMID:39993800 | DOI:10.21873/cgp.20502

Innovation (Camb). 2025 Jan 18;6(2):100773. doi: 10.1016/j.xinn.2024.100773. eCollection 2025 Feb 3.

ABSTRACT

Pharmacogenomic landscapes and related databases are important for identifying the biomarkers of drug response and toxicity. However, these data are still lacking for the Chinese population. In this study, we constructed a pharmacogenomic landscape and an associated database using whole-genome sequencing data generated by non-invasive prenatal testing in 206,640 Chinese individuals. In total, 1,577,513 variants (including 331,610 novel variants) were identified among 3,538 pharmacogenes related to 2,086 drugs. We found that the variant spectrum in the Chinese population differed among the seven major regions. Regional differences also exist among provinces in China. The average numbers of drug enzyme, transporter, and receptor variants were 258, 557, and 632, respectively. Subsequent correlation analysis indicated that the pharmacogenes affecting multiple drugs had fewer variants. Among the 16 categories of drugs, we found that nervous system, cardiovascular system, and genitourinary system/sex hormone drugs were more likely to be affected by variants of pharmacogenes. Characteristics of the variants in the enzyme, transporter, and receptor subfamilies showed specificity. To explore the clinical utility of these data, a genetic association study was conducted on 1,019 lung cancer patients. Two novel variants, AKT2 chr19:40770621 C>G and SLC19A1 chr21:46934171 A>C, were identified as novel platinum response biomarkers. Finally, a pharmacogenomic database, named the Chinese Pharmacogenomic Knowledge Base (CNPKB: http://www.cnpkb.com.cn/), was constructed to collect all the data. In summary, a pharmacogenomic landscape and database for the Chinese population were constructed in this study, which could support personalized Chinese medicine in the future.

PMID:39991480 | PMC:PMC11846038 | DOI:10.1016/j.xinn.2024.100773

Pan Afr Med J. 2024 Nov 14;49:79. doi: 10.11604/pamj.2024.49.79.42550. eCollection 2024.

ABSTRACT

The thirteenth conference of the African Society of Human Genetics with the theme "harnessing genomics and translational research to improve health in Africa" was held in Dar es Salaam, Tanzania, in August 2021, using a hybrid in-person and virtual model for participation in the wake of COVID-19 pandemic. During the meeting, African research across various human genetics disciplines was presented, including talks on the genetics of infectious and non-communicable diseases, population genetics, and translational research. The meeting also featured presentations on pharmacogenomics, genetics of developmental disorders, cancer genetics and genetics of rare diseases. In-depth discussions on ethical legal and social issues in genomics research and community and patient engagement were also key sessions of this meeting. The primary focus of the conference and the discussions was how to translate the wealth of genomic research in the continent into improved health outcomes in the continent. In this report, we summarize the key scientific research relevant to Africa presented and discussed during the meeting providing an overview of the progress of human genetics in the continent. We also discuss opportunities and challenges of harnessing genomics for health improvement in Africa.

PMID:39989936 | PMC:PMC11845995 | DOI:10.11604/pamj.2024.49.79.42550