Genes (Basel). 2025 Mar 24;16(4):371. doi: 10.3390/genes16040371.

ABSTRACT

Neuropsychiatric disorders are complex conditions with multifactorial etiologies, in which genetics play a pivotal role. Despite significant advancements in psychiatric research, traditional treatment options remain largely symptomatic, focusing on clinical signs without fully addressing the underlying biological causes. However, recent developments in precision medicine-an approach that tailors treatments based on genetic, environmental, and lifestyle factors-hold great promise for transforming the treatment of these disorders. By identifying specific genetic markers and understanding gene-environment interactions, precision medicine can offer more personalized and effective treatments, leading to better patient outcomes. Our primary aim was to explore how integrating genetic data with environmental factors could enhance the understanding and treatment of neuropsychiatric conditions such as schizophrenia, bipolar disorder, and depression. The secondary aim was to examine the potential of pharmacogenomics and gene therapy in improving therapeutic strategies. The results indicate that while significant progress has been made, challenges remain, including the complexity of genetic interactions and the need for more granular phenotypic data. In conclusion, precision medicine has the potential to revolutionize neuropsychiatric treatment by providing individualized care that considers genetic makeup, environmental influences, and lifestyle factors, paving the way for more effective therapies and improved patient outcomes.

PMID:40282331 | DOI:10.3390/genes16040371

Hum Genomics. 2025 Apr 25;19(1):44. doi: 10.1186/s40246-025-00753-6.

ABSTRACT

BACKGROUND: Statins are essential for managing cardiovascular disease (CVD), but adverse effects often lead to treatment discontinuation and non-adherence, underscoring the need for personalized approaches. This study aimed to evaluate the influence of pharmacogenomic (PGx) variants and demographic factors on statin-associated adverse effects in a multiethnic cohort from the United Arab Emirates (UAE).

METHODS: This sub-analysis of the EmHeart Study included 675 patients using rosuvastatin or atorvastatin. Patients were genotyped for SLCO1B1 and ABCG2 actionable variants using real-time PCR. Data on demographics, comorbidities, and statin use were extracted from electronic health records. Adverse events, including statin-associated muscle symptoms (SAMS) and liver enzyme elevation, were tracked over 12 months. Associations were analyzed using chi-square tests and logistic regression.

RESULTS: Rosuvastatin users carrying the ABCG2 rs2231142 variant had a threefold increased risk of liver enzyme elevation, particularly among East Asian patients (P < 0.005). Atorvastatin users with the SLCO1B1 rs4149056 variant exhibited a twofold increased risk of SAMS, with higher rates observed in females and Arabs (P < 0.05). The combination of rosuvastatin with ezetimibe further exacerbated risks of SAMS and liver enzyme elevation.

CONCLUSION: This study highlights the importance of genetic testing and demographic factors, such as ethnicity and gender, in tailoring statin therapy to minimize adverse effects. Despite extensive research on PGx-guided statin prescribing, clinical implementation remains limited. Integrating PGx testing into routine practice and enhancing physician awareness of genetic and demographic risk factors can improve the safety, efficacy, and adherence of lipid-lowering therapies in diverse populations.

PMID:40281622 | DOI:10.1186/s40246-025-00753-6

Pharmacogenomics J. 2025 Apr 25;25(3):12. doi: 10.1038/s41397-025-00371-4.

ABSTRACT

Pharmacogenomic testing for CYP2C19 helps personalise clopidogrel therapy and reduces the risk of experiencing a secondary myocardial infarction in individuals with impaired CYP2C19 function. Routine testing, however, is uncommon and it is proposed that the key requirements and processes of testing services are poorly understood. This scoping review aimed to explore the literature for CYP2C19 testing services for clopidogrel and identify their commonalities to inform the design and delivery of future services. In total, 37 eligible studies describing services across hospital and community settings were retrieved. Key elements of delivery included a multi-disciplinary approach involving physicians and pharmacists, provision of pre-implementation training and education, and electronic communication of test results. Result integration into clinical decision support systems improved the practical application of pharmacogenomic testing. The identification of the key requirements and processes may be used by institutions looking to design and deliver CYP2C19 testing services to guide clopidogrel therapy.

PMID:40280918 | DOI:10.1038/s41397-025-00371-4

Chem Biol Interact. 2025 Apr 23:111526. doi: 10.1016/j.cbi.2025.111526. Online ahead of print.

ABSTRACT

Pharmacogenetic (PGx) testing can be used to help guide drug therapy and decrease or avoid the risk of adverse drug reactions. CYP2D6 is an important pharmacogene in pharmacogenomics testing panels. However, phenoconversion, whereby an individual's ability to metabolize a drug does not match the genotype-predicted metabolizer status, is a confounding factor to the accurate application of PGx testing results to patient care. To address this issue, CYP2D6 expression between and within genotype-predicted CYP2D6 metabolizer phenotype groups was compared using WGS and RNA-Seq data from 134 normal liver tissue donors obtained from the GTEx program. Wide variability in CYP2D6 mRNA levels was observed within metabolizer phenotype groups. The median expression level for ultrarapid metabolizers (UMs) was 738.9 TPM (transcripts per million; 196.8-778.9 TPM), 212.5 TPM (32.1-666.5 TPM) for normal metabolizers (NMs), 219.6 TPM for intermediate metabolizers (IMs) (22-389.8 TPM), and 121.2 TPM for poor metabolizers (PMs) (9.3-298.2 TPM). The PM and UM phenotypes were significant predictors of CYP2D6 expression (p=0.0004 and p=0.019, respectively). Interestingly, expression of the gene encoding human serum albumin (ALB) was also a significant predictor of CYP2D6 expression (p=0.0003). Data from 50 patients with hepatocellular carcinoma obtained from the TCGA program showed no significant difference in expression between tumor tissue (median=119.7 TPM, range 0.16-817.7 TPM) and normal matched tissue (median=143.3 TPM, range 26.2-810.7 TPM). Transcriptional regulation of CYP2D6 expression may contribute to differences in drug response and risk for CYP2D6 phenoconversion. Efforts to understand the role of gene expression to predict CYP2D6 phenoconversion may inform the use of PGx testing in the clinical setting.

PMID:40280382 | DOI:10.1016/j.cbi.2025.111526

Life Sci. 2025 Apr 23:123661. doi: 10.1016/j.lfs.2025.123661. Online ahead of print.

ABSTRACT

AIMS: Arbutin (ARB), a natural polyphenol isolated from the bearberry plant Arctostaphylos uva-ursi, has been studied for its diverse pharmacological activities including anti-diabetic, cardioprotective and anti-inflammatory effects. This study aimed to evaluate arbutin's diuretic activity, focusing on its impact on aldosterone synthase gene expression and its toxicity profile.

MATERIAL AND METHODS: Acute toxicity was assessed using single doses ranging from 500 to 9000 mg/kg and sub-acute toxicity with doses of 375 and 750 mg/kg over 14 days. To evaluate acute diuretic activity, ARB was administered in three doses (25, 50 and 75 mg/kg i.p) alongside standard groups, furosemide (FUR) 10 mg/kg i.p and Spironolactone (SPIR) 25 mg/kg i.p. In sub-acute diuretic study, treatment was administered for seven days, followed by blood collection and adrenal dissection for gene expression analysis.

KEY FINDINGS: Acute toxicity studies revealed that ARB is well-tolerated up to 8000 mg/kg with no significant changes in organ and body weight. However, sub-acute studies showed minor changes in leukocyte count, alkaline phosphatase (ALP), alanine aminotransferase (ALT) and triglycerides (TGs) at high doses while histopathological evaluations revealed no severe organ damage. The diuretic index and electrolyte analysis confirmed the potential of ARB as diuretic and saluretic with reduced risk of hyperuricemia and hyperkalemia. Gene expression studies showed non-selective downregulation of aldosterone synthase gene (CYP11B2) and 11β-hydroxylase (CYP11B1). While the effects on 17α-hydroxylase (CYP17A1) were less pronounced than SPIR, indicating fewer possible anti-androgenic effects.

SIGNIFICANCE: Our findings suggest that ARB is a promising diuretic agent with a favorable safety profile.

PMID:40280300 | DOI:10.1016/j.lfs.2025.123661

J Allergy Clin Immunol. 2025 Apr 23:S0091-6749(25)00457-9. doi: 10.1016/j.jaci.2025.04.017. Online ahead of print.

ABSTRACT

BACKGROUND: Childhood asthma has been linked to distinct metabolomic profiles.

OBJECTIVE: To identify phenotypes (metabotypes) in children with moderate-to-severe asthma through integrative fecal and serum metabolome analysis.

METHODS: Children from the Systems Pharmacology Approach to Uncontrolled Pediatric Asthma cohort with Global Initiative for Asthma treatment step ≥3 were recruited. Asthma control was defined by the Asthma Control Test and annual exacerbation history. Targeted metabolomics profiling of feces and serum was performed using liquid chromatography and flow injection electrospray ionization-triple quadrupole mass spectrometry. Similarity Network Fusion integrated fecal and serum metabolome profiles, followed by spectral clustering. Clusters were analyzed for differences in asthma characteristics, food diaries, fecal microbiota composition, and levels of serum inflammatory markers and blood cells.

RESULTS: Integrative fecal and serum metabolome analysis of 92 children with moderate-to-severe asthma (median age: 11.5 years, 34% female) revealed three metabotypes. Metabotype1 had the lowest percentage of allergic rhinitis, with elevated serum ceramides and triglycerides. Metabotype2 had higher odds of asthma control, the highest percentage of children with ≥4 months of breastfeeding, reduced sugar intake, lowest levels of blood neutrophils and serum inflammatory markers, and with elevated serum acylcarnitines and ω-3 fatty acids. Metabotype3 included the highest percentage of uncontrolled asthma patients, with decreased serum cholesteryl esters, phosphatidylcholines, and sphingomyelins, elevated fecal amino acids, and reduced fecal microbiota diversity.

CONCLUSIONS: Metabotypes in children with moderate-to-severe asthma are linked to asthma control, distinct fecal microbiota and systemic inflammatory patterns. The findings suggest that metabotyping can be valuable in precision medicine approaches for asthma.

PMID:40280190 | DOI:10.1016/j.jaci.2025.04.017

J Pharm Biomed Anal. 2025 Apr 19;263:116910. doi: 10.1016/j.jpba.2025.116910. Online ahead of print.

ABSTRACT

Systemic arterial hypertension, affecting more than 1 billion people worldwide, necessitates widespread use of antihypertensive and diuretic medications. However, the potential toxicity related to exposure of these medications is not always fully understood, potentially leading to underestimates of deaths related to cardiovascular drugs. Additionally, the growing interest in monitoring adherence to antihypertensive medications necessitates the development of specific analytical methods suitable for both clinical and forensic applications. In this study, we developed a novel, high-throughput quantitative method for the simultaneous analysis of 21 antihypertensive and diuretic drugs mainly in human plasma using liquid chromatography with tandem mass spectrometry. This method has several advantages, including minimal sample volume requirement, a one-step sample preparation using an Ostro® plate, and a chromatographic run time of 7 min. The method was successfully validated on 11 criteria following the European Medicines Agency's guidances. The method was successfully applied to authentic samples from 62 clinical cases and 76 post-mortem cases, with two cases of severe intoxications more precisely described. The first case describes an attempted suicide by candesartan (2558 ng/mL in plasma) combined with celiprolol (18 ng/mL) and amlodipine (161 ng/mL). The second case is a diuretic-contaminated dietary supplement poisoning with plasma concentrations of 40 ng/mL for furosemide and 36 ng/mL for hydrochlorothiazide. The authors present a simple, fast, and sensitive quantification method for the analysis of 21 antihypertensive and diuretic drugs, with concentration values reported in both living subjects and post-mortem cases to aid in the often-challenging interpretation of cardiotropic drug concentrations.

PMID:40280085 | DOI:10.1016/j.jpba.2025.116910

Clin Transl Sci. 2025 May;18(5):e70230. doi: 10.1111/cts.70230.

ABSTRACT

Pharmacogenetic (PGx) testing can individualize pharmacotherapy, but many current panels lack inclusivity for diverse populations and are often cost-prohibitive for medically underserved communities. This study aimed to develop and validate GatorPGx Plus, a low-cost, preemptive PGx panel tailored for diverse patient populations. Pharmacogenes were selected based on the drug/drug classes potentially influenced by their variants, the clinical severity of drug-gene interactions, or the strength of guideline recommendations or emerging evidence. Variants within the pharmacogenes were included if their allele frequencies were approximately 1% or greater in any major ancestral population. The panel was validated for accuracy, precision, and analytical sensitivity and applied to 124 participants from an ongoing pharmacogenetic clinical implementation trial. To reduce costs, a high-throughput platform was chosen, laboratory technician hands-on time was minimized, and result translation and reporting were automated. The panel comprised tests for 62 variants in 14 genes/gene regions, including a CYP2D6 copy number assay. It demonstrated 100% concordance with reference methods. The average turnaround time between test order and results was 14.3 (±6.4) days. Among the 124 genotyped trial participants (mean age 60 years, 57.3% female), 99% had at least one non-normal function (less common or higher-risk) phenotype. The most frequently identified non-normal function phenotypes were in CYP2C19 (69.4%). CYP2D6 *17, *29, and CYP2C19 *9 were captured at higher frequencies than reported in European populations. GatorPGx Plus is a low per-test cost, clinically validated, preemptive PGx panel that effectively captures key variants in a mixed-ancestry population, underscoring its potential clinical utility in diverse, medically underserved populations.

PMID:40279185 | DOI:10.1111/cts.70230

Toxins (Basel). 2025 Apr 11;17(4):192. doi: 10.3390/toxins17040192.

ABSTRACT

Onabotulinumtoxin-A (onabotA) is a neurotoxin widely used for several indications, including chronic migraine (CM) preventive treatment, due to its well-demonstrated efficacy, tolerability, and safety. However, onabotA safety during pregnancy and breastfeeding remains unclear, as these populations are typically excluded from clinical trials. The action of onabotA starts locally at the injection sites, modulating the pain pathway with minimal systemic absorption, which theoretically minimizes risks to the fetus or breastfeeding infant. Preclinical studies demonstrate that onabotA does not distribute systemically in significant amounts after administration, although adverse fetal outcomes in rats and rabbits were reported when injected at high doses. Limited human data suggest that onabotA exposure during pregnancy may not be associated with major malformations or significant adverse outcomes for the fetus, especially when used at therapeutic doses for migraine prevention during the first trimester or earlier. Data on breastfeeding are even scarcer but indicate a low likelihood of drug transfer into breast milk. This narrative review highlights the available evidence on the use of onabotA in pregnancy and breastfeeding women, including real-word evidence, with a focus on the use for CM.

PMID:40278690 | DOI:10.3390/toxins17040192

J Pers Med. 2025 Apr 5;15(4):146. doi: 10.3390/jpm15040146.

ABSTRACT

Background: Pharmacogenomics (PGx) is the future of healthcare and implementation is being driven by increasing evidence. Understanding the workflow in a PGx clinic provides insight into the development and implementation of PGx services. It considers the patient's perspective, the role of the interprofessional team and the pivotal input of the pharmacist. Objectives: The purpose of this study was to describe the clinical workflow followed in selected PGx clinics. Methods: Four different sites that offer PGx clinical services (United States of America) were included. Qualitative data were collected through semi-structured interviews and observations providing valuable insights into the workflow followed in both community-based and hospital-based PGx clinics. Results: Although each setting differed, the processes were similar with setting-specific workflows and barriers. This study highlights the role of the pharmacist and the interprofessional team, the resources used for interpretation of PGx test results and the importance of patient and healthcare education. Conclusions: Understanding the workflow and the role of the interprofessional team in PGx is essential to ensure successful implementation and sustainable precision medicine practices in resource-limited settings.

PMID:40278324 | DOI:10.3390/jpm15040146

J Pers Med. 2025 Mar 27;15(4):128. doi: 10.3390/jpm15040128.

ABSTRACT

Individual variations in the active form of vitamin D (Vit.D) arise from a combination of dietary intake, sun exposure, and genetic factors, making it complex and challenging to maintain optimal levels. Among Vit.D-related genes, variations in CYP2R1 and CYP27B1 influence Vit.D synthesis, CYP24A1 regulates its inactivation, and the Vit.D receptor (VDR) mediates Vit.D signaling. These genetic variations contribute to substantial differences in Vit.D concentrations and associated clinical effects. However, there has been a lack of comprehensive, simultaneous exploration of these key genes and their clinical implications. This review provides a systematic analysis of genetic variants in Vit.D-related P450 genes identified in human clinical studies, along with in silico predictions of their functional consequences. Since multiple genes seem to influence the body's response to Vit.D, studying just one genetic variant may not fully explain Vit.D deficiency. A comprehensive evaluation of all Vit.D-related genes could offer valuable insights for advancing personalized medicine in Vit.D management. This study provides a foundation for developing a more personalized approach to Vit.D supplementation and regulation, guided by genetic information.

PMID:40278307 | DOI:10.3390/jpm15040128

Curr Oncol. 2025 Mar 31;32(4):204. doi: 10.3390/curroncol32040204.

ABSTRACT

Biological sex and gender factors significantly influence the pathogenesis, progression, and treatment response in hematologic malignancies. This comprehensive review examines sex-specific differences in acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, and multiple myeloma through systematic analysis of the peer-reviewed literature published between 2014-2024 and identified through structured searches of PubMed, Web of Science, and MEDLINE databases. Epidemiological data demonstrate higher disease incidence (57% male vs. 43% female in MM, 63% male vs. 37% female in AML hospitalizations for ages 18-39) and inferior outcomes in male patients across malignancy types (5-year relative survival rates of 48.8% vs. 60.4% in females with AML), while female patients exhibit superior survival despite experiencing greater treatment-related toxicities. Our analysis reveals consistent sex-specific patterns in molecular mechanisms, including distinct mutational profiles, differences in immune system function, and sex-based pharmacokinetic variations that collectively suggest the necessity for sex-differentiated treatment approaches. The review identifies reproducible patterns across diseases, particularly in cytogenetic and molecular characteristics, with females demonstrating favorable prognostic mutations in leukemias and higher rates of chromosomal abnormalities in multiple myeloma. Despite these identifiable patterns, significant knowledge gaps persist regarding the underlying mechanisms of sex-based outcome differences. Incorporating sex and gender considerations into precision medicine frameworks represents a critical advancement toward optimizing treatment strategies and improving clinical outcomes for patients with hematologic malignancies.

PMID:40277761 | DOI:10.3390/curroncol32040204

Cephalalgia. 2025 Apr;45(4):3331024251321500. doi: 10.1177/03331024251321500. Epub 2025 Apr 25.

ABSTRACT

We here present evidence-based guidelines for the pharmacological treatment of migraine. These guidelines, created by the Italian Society for the Study of Headache and the International Headache Society, aim to offer clear, actionable recommendations to healthcare professionals. They incorporate evidence-based recommendations from randomized controlled trials and expert-based opinions. The guidelines follow the GRADE approach for assessing the quality of evidence. The guideline development involved a systematic review of literature across multiple databases, adherence to Cochrane review methods, and a structured framework for data extraction and interpretation. Although the guidelines provide a robust foundation for migraine treatment, they also highlight gaps in current research, such as the paucity of head-to-head drug comparisons and the need for long-term outcome studies. These guidelines serve as a resource to standardize migraine treatment and promote high-quality care across different healthcare settings.

PMID:40277321 | DOI:10.1177/03331024251321500

Cephalalgia. 2025 Apr;45(4):3331024241305381. doi: 10.1177/03331024241305381. Epub 2025 Apr 25.

ABSTRACT

We here present evidence-based guidelines for the pharmacological treatment of migraine. These guidelines, created by the Italian Society for the Study of Headache and the International Headache Society, aim to offer clear, actionable recommendations to healthcare professionals. They incorporate evidence-based recommendations from randomized controlled trials and expert-based opinions. The guidelines follow the Grading of Recommendations, Assessment, Development and Evaluation approach for assessing the quality of evidence. The guideline development involved a systematic review of literature across multiple databases, adherence to Cochrane review methods, and a structured framework for data extraction and interpretation. Although the guidelines provide a robust foundation for migraine treatment, they also highlight gaps in current research, such as the paucity of head-to-head drug comparisons and the need for long-term outcome studies. These guidelines serve as a resource to standardize migraine treatment and promote high-quality care across different healthcare settings.

PMID:40277319 | DOI:10.1177/03331024241305381

Pharmacogenet Genomics. 2025 Apr 11. doi: 10.1097/FPC.0000000000000566. Online ahead of print.

ABSTRACT

OBJECTIVES: To explore the distribution of clinically relevant UGT1A1 polymorphisms and inferred UGT1A1 phenotypes in two Indigenous groups (Paiter-Suruí and Yanomami) from reservation areas in the Brazilian Amazon.

METHODS: Ninety-two Yanomami and 88 Paiter-Suruí were genotyped with a validated panel of ancestry informative markers. Individuals with >90% Native ancestry were genotyped for the promoter TA repeat (rs8175347) polymorphism and UGT1A1*6 (rs4148323) by direct sequencing, and for UGT1A1*80 (rs887829) by TaqMan allele discrimination. The UGT1A1 metabolic phenotypes were inferred from UGT1A1 diplotypes.

RESULTS: All Yanomami and 85 (96.6%) Paiter-Suruí had >92% Native ancestry. UGT1A1 genotype data from these individuals revealed: (i) the absence of both alleles with five and eight TA repeats [TA(5) and TA(8)]; (ii) TA(7) allele frequency of 0.470 in Yanomami and 0.441 in Paiter-Suruí; (iii) rs4148323 was absent in Paiter-Suruí and detected in two Yanomami (frequency 0.012); (iv) a perfect linkage disequilibrium (LD) between rs887829C>T and the promoter repeat polymorphisms in both cohorts: C allele with TA(6) and T allele with TA(7). The distribution of the inferred UGT1A1 metabolizer phenotypes did not differ between cohorts (Paiter-Suruí and Yanomami): the intermediate metabolizer was the most common (50.6-55.4%), followed by the normal (30.6-24.1%) and the slow (18.8-20.5%) phenotypes.

CONCLUSION: This is the first report on the frequency distribution of clinically relevant UGT1A1 variants and inferred UGT1A1 metabolic phenotypes in two major Native populations from indigenous reservation areas in the Brazilian Amazon, namely the Paiter-Suruí and Yanomami. The TA(5) and TA(8) repeats were absent, whereas TA(7) was common (frequency >0.50) in both cohorts. The intronic rs887829 variant (UGT1A1*80) single nucleotide variant was found in perfect LD with the promoter TA repeats. The rs4148323 SNP was absent (Paiter-Suruí) or rare (Yanomami). The frequency of high-risk UGT1A1 poor metabolizer phenotype was 1.6- to 2-fold higher in the indigenous cohorts compared to nonindigenous Brazilians.

PMID:40277150 | DOI:10.1097/FPC.0000000000000566

Curr Mol Med. 2025 Apr 24. doi: 10.2174/0115665240374044250416021616. Online ahead of print.

ABSTRACT

BACKGROUND: Chromobox 7 (CBX7) has been implicated in the progression of various malignant tumors, but its clinical relevance in lung adenocarcinoma (LUAD) remains poorly understood. This study aimed to investigate the expression, prognostic value, biological functions, and immunological role of CBX7 in LUAD.

METHODS: CBX7 expression in LUAD and adjacent normal tissues was analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Kaplan-Meier curves and Cox risk regression evaluated prognostic significance. Various algorithms assessed the correlation between CBX7 and immune microenvironment. The expression of CBX7 in LUAD tissues was detected by RT-qPCR, western blotting, and immunohistochemistry. The function of CBX7 in LUAD was further investigated by in vitro and in vivo experiments.

RESULTS: CBX7 expression significantly downregulated LUAD, which was associated with aberrant DNA methylation. Decreased CBX7 expression correlated with advanced tumor stage and poor prognosis. Notably, CBX7 is associated with immune cell infiltration and immune checkpoints, highlighting its potential role in guiding immunotherapy. Functional experiments demonstrated that CBX7 overexpression suppressed the malignant phenotype of LUAD cells, while CBX7 knockdown promoted tumor progression.

CONCLUSION: We conducted a systematic analysis of the diagnostic, prognostic, and immunological significance of CBX7 in LUAD, and found that it might serve as a diagnostic marker and therapeutic target in the future.

PMID:40277108 | DOI:10.2174/0115665240374044250416021616

Front Immunol. 2025 Apr 10;16:1543454. doi: 10.3389/fimmu.2025.1543454. eCollection 2025.

ABSTRACT

Gamma delta (γδ) T cells represent a unique and distinct population of lymphocytes that bridge the innate and adaptive immune responses. This functional duality positions them as one of the pivotal elements in the evolution and development of the human body's defense mechanisms. This review aims to provide a comprehensive and in-depth overview of γδ T cells, covering their origins, development, classification, and functional roles in immunology. Special attention is given to their involvement in the pathogenesis of autoimmune and cancer-related diseases-areas that remain subjects of intensive research with many unanswered questions. Additionally, this article explores the therapeutic potential of γδ T cells, which hold promise as a novel approach to treating various difficult-to-manage diseases. The review also presents an analysis of the latest clinical studies utilizing γδ T cells, emphasizing their emerging role in modern medicine. The ultimate goal of this work is to offer a holistic perspective on the current state of research on γδ T cells and their prospective applications in immunotherapy and cancer treatment, highlighting their potential to become a groundbreaking tool in future medical interventions.

PMID:40276509 | PMC:PMC12018481 | DOI:10.3389/fimmu.2025.1543454

Curr Pharm Teach Learn. 2025 Apr 23;17(7):102359. doi: 10.1016/j.cptl.2025.102359. Online ahead of print.

ABSTRACT

INTRODUCTION: Longitudinal curriculum has been suggested for improving pharmacogenomics education, however the outcome of such curriculum design has yet to be reported. Here we evaluated the effectiveness of a simple longitudinal curriculum consisting of didactic lecturing and laboratory-based teaching in two sequential semesters towards pharmacogenomics education.

METHODS: Four pharmacogenomics lectures were offered to professional year 3 (PY3) pharmacy students during the fall semester. During the following spring semester, students participated in two laboratories followed by an implementation project. Knowledge attainment was assessed through an exam following the fall lectures. Students' perception about their clinical pharmacogenomics skills were collected by electronic questionnaire before, immediately after, and 3 months after the fall lectures and the spring laboratories. Statistical analysis was performed using one-way ANOVA followed by pairwise t-test.

RESULTS: The average exam score in Fall 2023 was 79 % (54 %-96 %). Students' perception in a 1-5 Likert scale improved from 1.35 to 3.63 immediately following the lectures (p < 0.0001) but dropped to 1.94 after three months (p < 0.0001). In contrast, after two laboratories in Spring 2024, students' perception improved from 1.94 to 3.67 immediately following the laboratories (p < 0.0001), and importantly, remained high at 3.55 three months later (p = 0.36).

CONCLUSIONS: Combination of didactic lecturing and laboratory-based teaching offered in two sequential semesters is conducive to maintaining student's positive perception about their clinical pharmacogenomics skills. Our curriculum design is simple to implement and has the potential to improve long-term retention of pharmacogenomics knowledge.

PMID:40273885 | DOI:10.1016/j.cptl.2025.102359

Immunotherapy. 2025 Apr 24:1-8. doi: 10.1080/1750743X.2025.2493038. Online ahead of print.

ABSTRACT

PURPOSE: While CD33 directed immunotherapies have caught significant interest in recent years, the only approved antibody-drug conjugate targeting this antigen for AML is gemtuzumab ozogamicin, which targets the IgV-domain of CD33. Unfortunately, in its current form, these are not effective in a significant proportion of patients due to the presence of a splicing SNP resulting in the loss of IgV-domain. This, however, can be mitigated by targeting the IgC2-domain of CD33; thus, this study aimed to characterize CD33-D2 isoform using the recently developed CD33-D2-targeting antibody HL2541.

METHODS: Genetically engineered AML cell lines expressing CD33 isoforms were tested for antibody-bound internalization and response to GO in vitro. AML-bearing NSG-SGM3 mice were used to evaluate CD33-D2 localization and targeting by the HL2541 antibody in vivo.

RESULTS: HL2541-bound-CD33-D2 is internalized similar to CD33-FL upon binding the antibody component of GO. Co-existence of both isoforms compromises the internalization by >2.5-3-fold for each isoform in the AML cell lines, further resulting in 7-9.5-fold higher IC50 values compared to cells expressing only CD33-FL. Finally, we demonstrate that AML cells expressing CD33-D2 localize to bones in mice and are targeted by HL2541antibody in vivo.

CONCLUSION: The results establish the relevance of targeting IgC domain as an alternative immunotarget to supplement AML chemotherapy.

PMID:40272002 | DOI:10.1080/1750743X.2025.2493038

Front Psychiatry. 2025 Apr 9;16:1587875. doi: 10.3389/fpsyt.2025.1587875. eCollection 2025.

ABSTRACT

Depression is a complex and heterogeneous mental health disorder affecting an estimated 280 million individuals worldwide. Although various antidepressant medications are available, a significant proportion of patients experience medication-resistant depression. This clinical case report highlights the critical importance of integrating pharmacogenomics into clinical practice, which is still not routinely done in many countries, through the detailed examination of a mid-20s male patient diagnosed with medication-resistant depression. Genetic analysis revealed specific variations in the cytochrome P450 genes, namely CYP2D6, CYP2C19, and CYP1A2, which are crucial for drug metabolism. By investigating the impact of these genetic variations on the patient's treatment response, we provide evidence-based recommendations for adjusting antidepressant medications based on the individual's unique pharmacogenomic profile. As demonstrated in the case report, this ultimately results in a positive clinical outcome and would have been advantageous to implement earlier as part of the patient's management.

PMID:40270569 | PMC:PMC12014734 | DOI:10.3389/fpsyt.2025.1587875