Front Pharmacol. 2022 May 11;13:905375. doi: 10.3389/fphar.2022.905375. eCollection 2022.

ABSTRACT

DNA is always one of the most important targets for cancer therapy due to its leading role in the proliferation of cancer cells. Phototherapy kills cancer cells by generating reactive oxygen species (ROS) and local hyperthermia under light. It has attracted extensive interest in the clinical treatment of tumors because of many advantages such as non-invasiveness, high patient compliance, and low toxicity and side effects. However, the short ROS diffusion distance and limited thermal diffusion rate make it difficult for phototherapy to damage DNA deep in the nucleus. Therefore, nucleus-targeting phototherapy that can destroy DNAs via in-situ generation of ROS and high temperature can be a very effective strategy to address this bottleneck. Recently, some emerging nucleus-targeting phototherapy nanodrugs have demonstrated extremely effective anticancer effects. However, reviews in the field are still rarely reported. Here, we comprehensively summarized recent advances in nucleus-targeting phototherapy in recent years. We classified nucleus-targeting phototherapy into three categories based on the characteristics of these nucleus-targeting strategies. The first category is the passive targeting strategy, which mainly targets the nucleus by adjusting the physicochemical characteristics of phototherapy nanomedicines. The second category is to mediate the phototherapy nanodrugs into the nucleus by modifying functional groups that actively target the nucleus. The third category is to assist nanodrugs enter into the nucleus in a light-controlled way. Finally, we provided our insights and prospects for nucleus-targeting phototherapy nanodrugs. This minireview provides unique insights and valuable clues in the design of phototherapy nanodrugs and other nucleus-targeting drugs.

PMID:35645841 | PMC:PMC9130747 | DOI:10.3389/fphar.2022.905375

Int J Biol Markers. 2022 May 30:3936155221104128. doi: 10.1177/03936155221104128. Online ahead of print.

ABSTRACT

BACKGROUND: Several genetic association studies have analyzed the link between the catalase (CAT) C262T variant and different cancers, but the findings remain controversial. Our research centered on establishing a comprehensive correlation between the C262T variant and different cancers.

METHODS: This study was conducted using RevMan 5.4 software following the PRISMA 2020 guidelines. For this meta-analysis, 53 case-control studies (18,258 cases and 47,476 controls) were chosen.

RESULTS: The analysis revealed that three genetic models were statistically linked (P < 0.05) to overall cancer susceptibility in codominant model 2 (COD2): odds ratio (OR) = 1.16, COD3: OR = 1.21, recessive model (RM): OR = 1.20). After stratification by ethnicity, a significant link (P < 0.05) was found in Caucasians (COD2: OR = 1.18, COD3: OR = 1.17, over-dominant model (ODM): OR = 1.19) and Asians (COD3: OR = 1.49). Subgroup analyses revealed a significant correlation (P < 0.05) with blood-and-bone-marrow-related cancer, skin cancer, gastrointestinal-tract-related cancer, prostate cancer, and gynecologic cancer. Three genetic models in population-based controls (COD2: OR = 1.19, COD3: OR = 1.17, RM: OR = 1.19) and two genetic models in hospital-based controls (COD3: OR = 1.40, RM: OR = 1.24) were found to be significantly correlated (P < 0.05) with cancer. Also, three genetic models for polymerase chain reaction-restriction fragment length polymorphism (COD3: OR = 1.46; RM: OR = 1.34, ODM: OR = 0.80) and three models for MALDI-TOF + MassARRAY (COD2: OR = 1.32, RM: OR = 1.26, allele model: OR = 1.14) genotyping methods showed significant association (P < 0.05) with cancer. The meta-regression showed that the quality scores might be a source of significant heterogeneity under the COD2 model (coefficient = 0.176, P = 0.029). Trial sequential analysis also validated the adequacy of the sample size on overall findings.

CONCLUSION: Our results indicate that CAT C262T variant is associated with overall cancer susceptibility, especially in Caucasians and Asians. This variant may also be associated with blood-and-bone-marrow-related, GIT-related, prostate, skin, and gynecological cancers.

PMID:35645161 | DOI:10.1177/03936155221104128

Br J Clin Pharmacol. 2022 May 29. doi: 10.1111/bcp.15422. Online ahead of print.

ABSTRACT

AIM: The risk of ticagrelor-related bleeding events remains a major clinical concern, especially in East Asian populations. Previous studies have reported higher ticagrelor exposure in Asian patients than in Caucasians. This prompted us to investigate the correlation between ticagrelor concentrations and bleeding events.

METHODS: Patients diagnosed with acute coronary syndrome (ACS) and receiving dual antiplatelet therapy (aspirin and ticagrelor) were enrolled and followed up for 12 months. Trough plasma concentrations of ticagrelor and a major active metabolite were assayed, and 10 single nucleotide polymorphisms associated with ticagrelor pharmacokinetics and safety were also identified.

RESULTS: A total of 631 patients were included and 133 patients had bleeding academic research consortium (BARC) type 1 or 2 bleeding event. The median ticagrelor concentration (IQR) was significantly higher in patients with bleeding events than that in patients without bleeding events [322.6 ng/mL (196.2-458.0 ng/mL) vs 222.1 ng/mL (140.4-341.9 ng/mL), P = 1.66×10-7 ]. According to the receiver operating characteristic curve, the cut-off value for ticagrelor levels predicting bleeding events was 363.3 ng/mL (AUC =0.65; P = 1.66×10-7 , 95% Cl: 0.595-0.700). Pharmacogenomics results showed P2Y12 (rs6787801, P = 0.024) and P2Y12 (rs6785930, P = 0.048) were statistically associated with ticagrelor levels and bleeding events, respectively.

CONCLUSIONS: Ticagrelor plasma concentrations were associated with bleeding events in Chinese patients with ACS.

PMID:35644848 | DOI:10.1111/bcp.15422

Angew Chem Int Ed Engl. 2022 Jun 1. doi: 10.1002/anie.202203546. Online ahead of print.

ABSTRACT

Recent progress in studying copper-dependent targets and pathways in the context of tumor treatment has provided new insights into therapeutic strategies of leveraging copper-dependent disease vulnerabilities and pharmacologically manipulation of intratumor copper transportation to improve chemotherapy. Here, we developed ROS-sensitive nanoparticles loaded with copper chaperone inhibitor DC_AC50 and cisplatin(IV) prodrug. The released DC_AC50 can promote a remarkable accumulation of intracellular cisplatin and copper through inhibition of the Atox1-ATPase pathways, thereby enhancing the chemotherapeutic effect of cisplatin and inducing significant ROS generation. Excessive ROS then elicit intense endoplasmic reticulin (ER) stress which facilitates the immunogenic cell death (ICD) spurring a sustained immune response. Our study suggests that nanoparticle-mediated copper chaperone inhibition via DC_AC50 can restore the immunogenicity of tumor cells for enhanced chemotherapy and cancer immunotherapy.

PMID:35642869 | DOI:10.1002/anie.202203546

J Burn Care Res. 2022 May 10:irac062. doi: 10.1093/jbcr/irac062. Online ahead of print.

ABSTRACT

Management of critically ill patients requires simultaneous administration of many medications. Treatment for patient comorbidities may lead to drug-drug interactions which decrease drug efficacy or increase adverse reactions. Current practices rely on a one-size-fits-all dosing approach. Pharmacogenetic testing is generally reserved for addressing problems rather than used proactively to optimize care. We hypothesized that burn and surgery patients will have one or more genetic variants in drug metabolizing pathways used by one or more medications administered during the patient's hospitalization. The aim of this study was to determine the frequency of variants with abnormal function in the primary drug pathways and identify which medications may be impacted. Genetic (19 whole exome and 11 whole genome) and medication data from 30 pediatric burn and surgery patients were analyzed to identify pharmacogene-drug associations. Nineteen patients were identified with predicted altered function in one or more of the following genes: CYP2C9, CYP2C19, CYP2D6, and CYP3A4. The majority had decreased function, except for several patients with CYP2C19 rapid or ultrarapid variants. Some drugs administered during hospitalization that rely on these pathways include hydrocodone, oxycodone, methadone, ibuprofen, ketorolac, celecoxib, diazepam, famotidine, diphenhydramine, and glycopyrrolate. Approximately one-third of the patients tested had functionally impactful genotypes in each of the primary drug metabolizing pathways. This study suggests that genetic variants may in part explain the vast variability in drug efficacy and suggests that future pharmacogenetics research may optimize dosing regimens.

PMID:35639664 | DOI:10.1093/jbcr/irac062

J Med Toxicol. 2022 May 31. doi: 10.1007/s13181-022-00899-y. Online ahead of print.

NO ABSTRACT

PMID:35639281 | DOI:10.1007/s13181-022-00899-y

Transl Psychiatry. 2022 May 30;12(1):214. doi: 10.1038/s41398-022-01963-5.

NO ABSTRACT

PMID:35637185 | DOI:10.1038/s41398-022-01963-5

J Hepatol. 2022 May 27:S0168-8278(22)00333-6. doi: 10.1016/j.jhep.2022.05.018. Online ahead of print.

ABSTRACT

BACKGROUND & AIMS: Acute intermittent porphyria (AIP), caused by heterozygous germline mutations of the heme synthesis pathway enzyme HMBS (hydroxymethylbilane synthase), confers high risk of hepatocellular carcinoma (HCC) development. Yet, the role of HMBS in liver tumorigenesis remains unclear.

METHODS: Here we explore HMBS alterations in a large series of 758 HCC including 4 AIP patients, we quantify the impact of HMBS mutations on heme biosynthesis pathway intermediates and we investigate the molecular and clinical features of HMBS-mutated tumors.

RESULTS: We identify recurrent bi-allelic HMBS inactivation, both in AIP patients acquiring a second somatic HMBS mutation and in sporadic HCC with two somatic hits. HMBS alterations are enriched in truncative mutations, in particular in splice regions, leading to abnormal transcript structures. Bi-allelic HMBS inactivation results in a massive accumulation of its toxic substrate porphobilinogen and synergizes with CTNNB1 activating mutations, leading to the development of well differentiated tumors with a transcriptomic signature of Wnt/ß-catenin pathway activation and a DNA methylation signature related to ageing. HMBS-inactivated HCC mostly affect females, in absence of fibrosis and classical HCC risk factors.

CONCLUSIONS: These data identify HMBS as a tumor suppressor gene whose bi-allelic inactivation defines a homogenous clinical and molecular HCC subtype.

LAY SUMMARY: Heme synthesis occurs in the liver and involves several enzymes including hydroxymethylbilane synthase (HMBS). HMBS mutations cause acute intermittent porphyria, a disease caused by the accumulation of toxic porphyrin precusors. Here we show that HMBS inactivation is also involved in the development of hepatocellular carcinomas with distinct clinical and molecular characteristics.

PMID:35636578 | DOI:10.1016/j.jhep.2022.05.018

J Epidemiol Glob Health. 2022 May 28. doi: 10.1007/s44197-022-00045-5. Online ahead of print.

ABSTRACT

BACKGROUND: Hunan Province is a region in China with a high prevalence of intracerebral hemorrhage, especially primary intracerebral hemorrhage (PICH). The objective of this observational study was to assess the disease burden of PICH.

METHODS: We searched the Hunan Provincial Health Statistics Direct Reporting and Decision Analysis System to retrieve PICH inpatient and outpatient data and all-population all-cause deaths in Hunan Province in 2018. DisMod II was used to estimate the disability-adjusted life years (DALYs) due to PICH in 2018.

RESULTS: In 2018, 30,400 new PICH cases were recorded in Hunan Province. The incidence was higher among men (51.6 per 100,000) than women (29.3 per 100,000). The DALYs due to PICH were 478,000 patient-years, the years of life lost (YLLs) were 452,000 patient-years and the years lived with disability (YLDs) were 27,000 patient-years. In 2018, the rate of DALYs due to PICH was 6.4 patient-years per 1000 individuals, the rate of YLLs was 6.1 patient-years per 1000 individuals, and the rate of YLDs was 0.3 patient-years per 1000 individuals.

CONCLUSION: We estimated the DALYs due to PICH in Hunan Province in 2018, thereby providing relevant data for the development of policies and measures for the management of PICH disease burden.

PMID:35633483 | DOI:10.1007/s44197-022-00045-5

Pharmaceutics. 2022 May 5;14(5):990. doi: 10.3390/pharmaceutics14050990.

ABSTRACT

Standard tuberculosis (TB) management has failed to control the growing number of drug-resistant TB cases worldwide. Therefore, innovative approaches are required to eradicate TB. Model-informed precision dosing and therapeutic drug monitoring (TDM) have become promising tools for adjusting anti-TB drug doses corresponding with individual pharmacokinetic profiles. These are crucial to improving the treatment outcome of the patients, particularly for those with complex comorbidity and a high risk of treatment failure. Despite the actual benefits of TDM at the bedside, conventional TDM encounters several hurdles related to laborious, time-consuming, and costly processes. Herein, we review the current practice of TDM and discuss the main obstacles that impede it from successful clinical implementation. Moreover, we propose a semi-automated TDM approach to further enhance precision medicine for TB management.

PMID:35631576 | DOI:10.3390/pharmaceutics14050990

Pharmaceutics. 2022 Apr 27;14(5):944. doi: 10.3390/pharmaceutics14050944.

ABSTRACT

Statins are the first-line treatment for familial hypercholesterolemia (FH), but response is highly variable due to genetic and nongenetic factors. Here, we explored the association between response and genetic variability in 114 Brazilian adult FH patients. Specifically, a panel of 84 genes was analyzed by exon-targeted gene sequencing (ETGS), and the functional impact of variants in pharmacokinetic (PK) genes was assessed using an array of functionality prediction methods. Low-density lipoprotein cholesterol (LDL-c) response to statins (reduction ≥ 50%) and statin-related adverse event (SRAE) risk were assessed in carriers of deleterious variants in PK-related genes using multivariate linear regression analyses. Fifty-eight (50.8%) FH patients responded to statins, and 24 (21.0%) had SRAE. Results of the multivariate regression analysis revealed that ABCC1 rs45511401 significantly increased LDL-c reduction after statin treatment (p &lt; 0.05). In silico analysis of the amino-acid change using molecular docking showed that ABCC1 rs45511401 possibly impairs statin efflux. Deleterious variants in PK genes were not associated with an increased risk of SRAE. In conclusion, the deleterious variant ABCC1 rs45511401 enhanced LDL-c response in Brazilian FH patients. As such, this variant might be a promising candidate for the individualization of statin therapy.

PMID:35631530 | DOI:10.3390/pharmaceutics14050944

Pharmaceuticals (Basel). 2022 May 22;15(5):637. doi: 10.3390/ph15050637.

ABSTRACT

In the field of pharmacogenetics, the trend is to analyze a panel of several actionable genetic polymorphisms. It may require the use of high-throughput sequencing which demands expensive reagents/instruments and specific skills to interpret results. As an alternative, the aim of this work was to validate an easy, fast, and inexpensive multiplex pharmacogenetics assay to simultaneously genotype a panel of 17 clinically actionable variants involved in drug pharmacokinetics/pharmacodynamics. We designed primers to perform a multiplex PCR assay using a single mix. Primers were labeled by two fluorescent dye markers to discriminate alleles, while the size of the PCR fragments analyzed by electrophoresis allowed identifying amplicon. Polymorphisms of interest were CYP3A4*22, CYP3A5*3, CYP1A2*1F, CYP2C9*2-*3, CYP2C19*2-*3-*17, VKORC1-1639G &gt; A, ABCB1 rs1045642-rs1128503-rs2229109-rs2032582, and CYP2D6*3-*4-*6-*9. The assay was repeatable and a minimum quantity of 10 ng of DNA/ sample was needed to obtain accurate results. The method was applied to a validation cohort of 121 samples and genotyping results were consistent with those obtained with reference methods. The assay was fast and cost-effective with results being available within one working-day. This robust assay can easily be implemented in laboratories as an alternative to cumbersome simplex assays or expensive multiplex approaches. Together it should widespread access to pharmacogenetics in clinical routine practice.

PMID:35631462 | DOI:10.3390/ph15050637

Pharmaceuticals (Basel). 2022 May 20;15(5):630. doi: 10.3390/ph15050630.

ABSTRACT

Vitamin D (VD) seems to influence drug clearance and outcome. Antifungal drugs (AFU) are the most used azoles in clinical practice. In the literature, no data are available concerning VD's impact on AFU therapy. The aim of this study was to analyze if VD pathway-related polymorphisms may influence voriconazole (VRC), itraconazole (ITC), and posaconazole (PSC) drug concentrations in order to identify patients with the highest probability of response and toxicity. Allelic discrimination was performed through real-time PCR, whereas drug concentrations were through liquid chromatography. A total of 636 samples of AFU-treated patients were included in the analysis. Concerning VRC, concentrations higher than the 1000 ng/mL efficacy cut-off value were predicted by Caucasian ethnicity, CYP24A1 3999, and CYP27B1 + 2838 polymorphisms, whereas levels higher than the 5000 ng/mL toxicity value by Caucasian, female sex, e.v. administration, and GC 1296. Considering PSC, concentrations higher than the 700 ng/mL efficacy cut-off value were predicted by VDR Cdx2, CYP27B1 - 1260, and GC 1296. Finally, for ITC, VDR BsmI was the only predictor of drug exposure higher than the 500 ng/mL efficacy cut-off value, whereas female sex, CYP27B1 - 1260, and VDR TaqI remained in the final regression model related to concentrations higher than the 1000 ng/mL toxicity-associated cut-off value. This is the first study reporting the influence of VD pathway-related gene SNPs on AFU exposures, efficacy, and toxicity.

PMID:35631455 | DOI:10.3390/ph15050630

Nutrients. 2022 May 11;14(10):2022. doi: 10.3390/nu14102022.

ABSTRACT

BACKGROUND: One of the main features of Alzheimer's disease (AD) pathology is failure in innate immune response and chronic inflammation. Lack of effective AD treatment means that more attention is paid to alternative therapy and drugs of natural origin, such as extract of Ginkgo biloba (EGb). The purpose of this study was to investigate the effect of EGb on the mechanisms of innate immune response of peripheral blood leukocytes (PBLs) in AD patients.

METHODS: In AD patients and healthy-age matched controls, the effect of EGb on two of innate immune reactions, i.e., PBLs resistance to viral infection ex vivo and production of cytokines, namely TNF-α, IFN-γ, IL-1β, IL-10, IL-15, and IFN-α, were investigated. The influence of EGb on inflammatory-associated genes expression that regulate innate immune response to viral infection and cytokine production, namely IRF-3, IRF-7, tetherin, SOCS1, SOCS3, NFKB1, p65, and MxA was also examined.

RESULTS: A beneficial effect of EGb especially in AD women was observed. EGb decreased production of TNF-α, IFN-γ, and IL-10 and increased IL-15 and IL-1β. The effect was more pronouncement in AD group. EGb also downregulated expression of investigated genes.

CONCLUSIONS: EGb may have an advantageous properties for health management in elderly and AD sufferers but especially in women with AD. Improving peripheral innate immune cells' activity by adding EGb as accompanying treatment in AD may be, in the long term, a good course to modify the disease progression.

PMID:35631163 | DOI:10.3390/nu14102022

Molecules. 2022 May 20;27(10):3302. doi: 10.3390/molecules27103302.

ABSTRACT

Dried Prunus spinosa fruits (sloes) are folk phytotherapeutics applied to treat chronic inflammatory disorders. However, their pharmacological potential, activity vectors, and drying-related changes in bioactive components remain unexplored. Therefore, the present research aimed to evaluate the anti-inflammatory and antioxidant effects of dried sloes in ex vivo models of human neutrophils and peripheral blood mononuclear cells (PMBCs) and establish their main active components. It was revealed that the fruit extracts significantly and dose-dependently inhibited the respiratory burst, downregulated the production of elastase (ELA-2) and TNF-α, and upregulated the IL-10 secretion by immune cells under pro-inflammatory and pro-oxidant stimulation. The slightly reduced IL-6 and IL-8 secretion was also observed. The structural identification of active compounds, including 45 phenolics and three Maillard reaction products (MRPs) which were formed during drying, was performed by an integrated approach combining LC-MS/MS, preparative HPLC isolation, and NMR studies. The cellular tests of four isolated model compounds (chlorogenic acid, quercetin, procyanidin B2, and 5-hydroxymethylfurfural), supported by statistical correlation studies, revealed a significant polyphenolic contribution and a slight impact of MRPs on the extracts' effects. Moreover, a substantial synergy was observed for phenolic acids, flavonoids, condensed proanthocyanidins, and MPRs. These results might support the phytotherapeutic use of dried P. spinosa fruits to relieve inflammation and establish the quality control procedure for the extracts prepared thereof.

PMID:35630778 | DOI:10.3390/molecules27103302

J Pers Med. 2022 May 19;12(5):823. doi: 10.3390/jpm12050823.

ABSTRACT

Cytochrome P450 (CYP) enzymes, such as CYP3A4, and CYP3A5, P450 oxidoreductase (POR), peroxisome proliferator activated receptor alpha (PPAR-alpha), and drug transporter (ABCB1) were observed to influence concentrations of immunosuppressants (cyclosporine, everolimus, sirolimus, and tacrolimus) and outcomes in renal transplants. We carried out the present study to evaluate the prevalence and impact of these single nucleotide polymorphisms (SNPs) in adult renal transplants. SNPs were evaluated using commercial TaqMan® assays. Serum drug concentrations were estimated using immunoassays. One hundred and forty-six patients were recruited. SNPs in CYP3A5*3 were significantly associated with greater dose-adjusted cyclosporine and tacrolimus concentrations. SNPs in POR*28 were observed with significantly lower dose-adjusted concentrations, particularly with cyclosporine and tacrolimus. ABCB1 homozygous polymorphisms were observed with significantly lower time spent in the therapeutic range with cyclosporine and everolimus/sirolimus. Cyclosporine was observed in a significantly greater proportion of patients with elevated GGT, and SNPs in PPAR-alpha were significantly associated with an increased risk of this adverse event. Hypertriglyceridemia with everolimus was significantly associated with POR*28 polymorphisms. There is a need to validate the influence of these SNPs in a prospective study and develop an algorithm predicting the achievement of target concentrations.

PMID:35629245 | DOI:10.3390/jpm12050823

J Pers Med. 2022 May 13;12(5):788. doi: 10.3390/jpm12050788.

ABSTRACT

Donepezil and memantine are the most common drugs used for Alzheimer's disease. Their low effectiveness could partly be explained by genetic factors. Thus, we aim to identify Single Nucleotide Polymorphisms (SNPs) associated with pharmacokinetics, pharmacodynamics, and the safety of donepezil and memantine. For this regard, 25 volunteers enrolled in a bioequivalence clinical trial were genotyped for 67 SNPs in 21 genes with a ThermoFisher QuantStudio 12K Flex OpenArray. The statistical strategy included a univariate analysis that analyzed the association of these SNPs with pharmacokinetic parameters or the development of adverse drug reactions (ADRs) followed by a Bonferroni-corrected multivariate regression. Statistical analyses were performed with SPSS software v.21 and R commander (version v3.6.3). In the univariate analysis, fourteen and sixteen SNPs showed a significant association with memantine's and donepezil's pharmacokinetic parameters, respectively. Rs20417 (PTGS2) was associated with the development of at least one ADR. However, none of these associations reached the significance threshold in the Bonferroni-corrected multivariate analysis. In conclusion, we did not observe any significant association of the SNPs analyzed with memantine and donepezil pharmacokinetics or ADRs. Current evidence on memantine and donepezil pharmacogenetics does not justify their inclusion in pharmacogenetic guidelines.

PMID:35629210 | DOI:10.3390/jpm12050788

J Pers Med. 2022 Apr 29;12(5):720. doi: 10.3390/jpm12050720.

ABSTRACT

Acetaminophen (paracetamol) is a widely used drug that causes adverse drug events that are often dose-dependent and related to plasma drug concentrations. Acetaminophen metabolism strongly depends on UGT1A enzymes. We aimed to investigate putative factors influencing acetaminophen pharmacokinetics. We analyzed acetaminophen pharmacokinetics after intravenous administration in 186 individuals, and we determined the effect of sex; body mass index (BMI); previous and concomitant therapy with UGT1A substrates, inhibitors, and inducers; as well as common variations in the genes coding for UGT1A1, UGT1A6, and UGT1A9. We identified sex and UGT1A6 genetic variants as major factors influencing acetaminophen pharmacokinetics, with women showing lower clearance (p &lt; 0.001) and higher area under the plasma drug concentration-time curve (AUC) values than men (p &lt; 0.001). UGT1A6 genetic variants were related to decreased acetaminophen biodisposition. Individuals who were homozygous or double-heterozygous for variant UGT1A6 alleles showed a 22.5% increase in t1/2 values and a 22.8 increase in drug exposure (p &lt; 0.001, and 0.006, respectively) after correction by sex. The effect is related to the UGT1A6*2 and UGT1A6*4 variant alleles, whereas no effect of UGT1A6*3 and UGT1A9*3 alleles, BMI, or drug-drug interaction was identified in this study. We conclude that sex and UGT1A6 variants determine acetaminophen pharmacokinetics, thus providing evidence to eventually developing pharmacogenomics procedures and recommendations for acetaminophen use.

PMID:35629143 | DOI:10.3390/jpm12050720

J Pers Med. 2022 Apr 22;12(5):673. doi: 10.3390/jpm12050673.

ABSTRACT

Both personalized medicine and nanomedicine are new to medical practice. Nanomedicine is an application of the advances of nanotechnology in medicine and is being integrated into diagnostic and therapeutic tools to manage an array of medical conditions. On the other hand, personalized medicine, which is also referred to as precision medicine, is a novel concept that aims to individualize/customize therapeutic management based on the personal attributes of the patient to overcome blanket treatment that is only efficient in a subset of patients, leaving others with either ineffective treatment or treatment that results in significant toxicity. Novel nanomedicines have been employed in the treatment of several diseases, which can be adapted to each patient-specific case according to their genetic profiles. In this review, we discuss both areas and the intersection between the two emerging scientific domains. The review focuses on the current situation in personalized medicine, the advantages that can be offered by nanomedicine to personalized medicine, and the application of nanoconstructs in the diagnosis of genetic variability that can identify the right drug for the right patient. Finally, we touch upon the challenges in both fields towards the translation of nano-personalized medicine.

PMID:35629095 | DOI:10.3390/jpm12050673

J Clin Med. 2022 May 20;11(10):2912. doi: 10.3390/jcm11102912.

ABSTRACT

BACKGROUND: Axial spondyloarthritis (axSpA) is a chronic inflammatory condition of the spine. In addition to musculoskeletal symptoms, there are also extra-articular manifestations. The aim of this study was to search for new biomarkers associated with the clinical presentation and treatment response in axSpA patients.

METHODS: In this study, 106 axSpA patients and 110 healthy controls were enrolled. Six single-nucleotide polymorphisms (SNPs) were selected for genotyping: ERAP1 rs2287987, ERAP2 rs2549782, TNF rs1800629, TNFRSF1A rs767455, TNFRSF1B rs1061622, and FCGR2A rs1801274. Participants were examined at baseline and after 12 and 24 weeks of anti-TNF therapy.

RESULTS: SNPs associated with high axSpA initial activity were TNFRSF1A rs767455 and TNFRSF1B rs1061622 (p &lt; 0.008). The ERAP1 rs2287987 AA genotype was more frequently observed in patients with enthesitis (AA vs. G+, p = 0.049), while the TNFRSF1B rs1061622 GG genotype was more common in participants with uveitis (GG vs. TT, p = 0.042). Potential in predicting anti-TNF treatment response was demonstrated by ERAP1 rs2287987, ERAP2 rs2549782, TNFRSF1B rs1061622, and FCGR2A rs1801274.

CONCLUSIONS: SNPs can be used to identify patients at risk of severe disease to initiate treatment earlier. Genetic testing will allow clinicians to choose the right drug for the patient.

PMID:35629038 | DOI:10.3390/jcm11102912