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PeerJ 2024The method currently available to diagnose shigellosis is insensitive and has many limitations. Thus, this study was designed to identify specific antigenic protein(s)...
BACKGROUND
The method currently available to diagnose shigellosis is insensitive and has many limitations. Thus, this study was designed to identify specific antigenic protein(s) among the cell surface associated proteins (SAPs) of that would be valuable in the development of an alternative diagnostic assay for shigellosis, particularly one that could be run using a stool sample rather than serum.
METHODS
The SAPs of clinical isolates of S. , , and were extracted from an overnight culture grown at 37 °C using acidified-glycine extraction methods. Protein profiles were observed by SDS-PAGE. To determine if antibodies specific to certain SAPs were present in both sera and stool suspensions, Western blot analysis was used to detect the presence of IgA, IgG, and IgM.
RESULTS
Immunoblot analysis revealed that sera from patients infected with . recognized 31 proteins. These SAP antigens are recognized by the host humoral response during infection. Specific antibodies against these antigens were also observed in intestinal secretions of shigellosis patients. Of these 31 proteins, the 35 kDa protein specifically reacted against IgA present in patients' stool suspensions. Further study illustrated the immunoreactivity of this protein in , and . This is the first report that demonstrates the presence of immunoreactive SAPs in stool suspensions. The SAPSs could be very useful in developing a simple and rapid serodiagnostic assay for shigellosis directly from stool specimens.
Topics: Humans; Feces; Dysentery, Bacillary; Shigella flexneri; Bacterial Proteins; Antibodies, Bacterial; Antigens, Bacterial; Blotting, Western; Electrophoresis, Polyacrylamide Gel; Immunoglobulin A
PubMed: 38827305
DOI: 10.7717/peerj.17498 -
The Pharmacogenomics Journal Jun 2024The aim was to determine if opioid neuroimmunopharmacology pathway gene polymorphisms alter serum morphine, morphine-3-glucuronide and morphine-6-glucuronide...
The aim was to determine if opioid neuroimmunopharmacology pathway gene polymorphisms alter serum morphine, morphine-3-glucuronide and morphine-6-glucuronide concentration-response relationships in 506 cancer patients receiving controlled-release oral morphine. Morphine-3-glucuronide concentrations (standardised to 11 h post-dose) were higher in patients without pain control (median (interquartile range) 1.2 (0.7-2.3) versus 1.0 (0.5-1.9) μM, P = 0.006), whereas morphine concentrations were higher in patients with cognitive dysfunction (40 (20-81) versus 29 (14-60) nM, P = 0.02). TLR2 rs3804100 variant carriers had reduced odds (adjusted odds ratio (95% confidence interval) 0.42 (0.22-0.82), P = 0.01) of opioid adverse events. IL2 rs2069762 G/G (0.20 (0.06-0.52)), BDNF rs6265 A/A (0.15 (0.02-0.63)) and IL6R rs8192284 carrier (0.55 (0.34-0.90)) genotypes had decreased, and IL6 rs10499563 C/C increased (3.3 (1.2-9.3)), odds of sickness response (P ≤ 0.02). The study has limitations in heterogeneity in doses, sampling times and diagnoses but still suggests that pharmacokinetics and immune genetics co-contribute to morphine pain control and adverse effects in cancer patients.
Topics: Humans; Morphine; Male; Female; Cancer Pain; Middle Aged; Analgesics, Opioid; Delayed-Action Preparations; Aged; Pharmacogenetics; Polymorphism, Single Nucleotide; Morphine Derivatives; Adult; Pharmacogenomic Variants; Toll-Like Receptor 2
PubMed: 38824169
DOI: 10.1038/s41397-024-00339-w -
The Journal of International Medical... May 2024Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) is currently used in clinical microbiology laboratories. This study aimed to...
OBJECTIVE
Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) is currently used in clinical microbiology laboratories. This study aimed to determine whether dual-polarity time-of-flight mass spectrometry (DP-TOF MS) could be applied to clinical nucleotide detection.
METHODS
This prospective study included 40 healthy individuals and 110 patients diagnosed with cardiovascular diseases. We used DP-TOF MS and Sanger sequencing to evaluate 17 loci across 11 genes associated with cardiovascular drug responses. In addition, we used DP-TOF MS to test 998 retrospectively collected clinical DNA samples with known results.
RESULTS
A, T, and G nucleotide detection by DP-TOF MS and Sanger sequencing revealed 100% concordance, whereas the C nucleotide concordance was 99.86%. Genotyping based on the results of the two methods showed 99.96% concordance. Regarding clinical applications, DP-TOF MS yielded a 99.91% concordance rate for known loci. The minimum detection limit for DNA was 0.4 ng; the inter-assay and intra-assay precision rates were both 100%. Anti-interference analysis showed that aerosol contamination greater than 10 copies/µL in the laboratory environment could influence the results of DP-TOF MS.
CONCLUSIONS
The DP-TOF MS platform displayed good detection performance, as demonstrated by its 99.96% concordance rate with Sanger sequencing. Thus, it may be applied to clinical nucleotide detection.
Topics: Humans; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Female; Male; Prospective Studies; Cardiovascular Diseases; Middle Aged; Adult; Aged; Sequence Analysis, DNA; DNA; Retrospective Studies; Case-Control Studies; Polymorphism, Single Nucleotide
PubMed: 38819085
DOI: 10.1177/03000605241255568 -
Clinical and Translational Science Jun 2024Pharmacogenetic (PGx)-informed medication prescription is a cutting-edge genomic application in contemporary medicine, offering the potential to overcome the... (Review)
Review
Pharmacogenetic (PGx)-informed medication prescription is a cutting-edge genomic application in contemporary medicine, offering the potential to overcome the conventional "trial-and-error" approach in drug prescription. The ability to use an individual's genetic profile to predict drug responses allows for personalized drug and dosage selection, thereby enhancing the safety and efficacy of treatments. However, despite significant scientific and clinical advancements in PGx, its integration into routine healthcare practices remains limited. To address this gap, the Qatar Genome Program (QGP) has embarked on an ambitious initiative known as QPGx-CARES (Qatar Pharmacogenetics Clinical Applications and Research Enhancement Strategies), which aims to set a roadmap for optimizing PGx research and clinical implementation on a national scale. The goal of QPGx-CARES initiative is to integrate PGx testing into clinical settings with the aim of improving patient health outcomes. In 2022, QGP initiated several implementation projects in various clinical settings. These projects aimed to evaluate the clinical utility of PGx testing, gather valuable insights into the effective dissemination of PGx data to healthcare professionals and patients, and identify the gaps and the challenges for wider adoption. QPGx-CARES strategy aimed to integrate evidence-based PGx findings into clinical practice, focusing on implementing PGx testing for cardiovascular medications, supported by robust scientific evidence. The current initiative sets a precedent for the nationwide implementation of precision medicine across diverse clinical domains.
Topics: Humans; Qatar; Pharmacogenetics; Precision Medicine; Pharmacogenomic Testing
PubMed: 38818903
DOI: 10.1111/cts.13800 -
World Journal of Hepatology May 2024Hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infection still involves 2.3 million patients worldwide of the estimated 37.7 million living with HIV,...
Hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infection still involves 2.3 million patients worldwide of the estimated 37.7 million living with HIV, according to World Health Organization. People living with HIV (PLWH) are six times greater affected by HCV, compared to HIV negative ones; the greater prevalence is encountered among people who inject drugs and men who have sex with men: the risk of HCV transmission through sexual contact in this setting can be increased by HIV infection. These patients experience a high rate of chronic hepatitis, which if left untreated progresses to end-stage liver disease and hepatocellular carcinoma (HCC) HIV infection increases the risk of mother to child vertical transmission of HCV. No vaccination against both infections is still available. There is an interplay between HIV and HCV infections. Treatment of HCV is nowadays based on direct acting antivirals (DAAs), HCV treatment plays a key role in limiting the progression of liver disease and reducing the risk of HCC development in mono- and coinfected individuals, especially when used at an early stage of fibrosis, reducing liver disease mortality and morbidity. Since the sustained virological response at week 12 rates were observed in PLWH after HCV eradication, the AASLD has revised its simplified HCV treatment algorithm to also include individuals living with HIV. HCV eradication can determine dyslipidemia, since HCV promotes changes in serum lipid profiles and may influence lipid metabolism. In addition to these apparent detrimental effects on the lipid profile, the efficacy of DAA in HCV/HIV patients needs to be considered in light of its effects on glucose metabolism mediated by improvements in liver function. The aim of the present editorial is to describe the advancement in HCV treatment among PLWH.
PubMed: 38818300
DOI: 10.4254/wjh.v16.i5.661 -
Saudi Pharmaceutical Journal : SPJ :... Jul 2024L. has been traditionally used for treating snakebites and is known to possess antifebrile and hemostatic properties. These properties are closely related to wound...
L. has been traditionally used for treating snakebites and is known to possess antifebrile and hemostatic properties. These properties are closely related to wound healing. This study aimed to evaluate the wound healing properties of leaves extract (BFLE) in vitro and in vivo. The in vitro study focused on proliferation, migration, and expression of TGF-β, IL-1β, VEGF, and MMP-2 genes and proteins. The in vivo study included excisional wound healing, histology, and tensile strength studies. The ethanolic extract of (BFLE) was tested for its effects on proliferation and migration using keratinocytes (HaCaT) and fibroblasts (BJ) cells. Gene and protein expression related to wound healing were analyzed using real-time PCR and Western blot assays. The wound healing properties of BFLE were evaluated in vivo using Wistar albino rats, focusing on excisional wound healing, histology, and tensile strength studies. The BFLE displayed significant proliferative and migratory effects on keratinocytes and fibroblasts cells, while upregulating the expression of TGF-β, IL-1β, VEGF, and MMP-2 genes and proteins. BFLE also exhibited significant wound healing effects on Wistar albino rats' excisional wounds and improved the overall tensile strength. The results suggest that BFLE has strong wound healing properties, as demonstrated by its ability to increase keratinocytes and fibroblasts proliferation and migration, upregulate genes and proteins involved in the wound healing process, and improve wound healing rates and tensile strength. The findings of this study provide important insights into the potential use of as a natural wound healing agent.
PubMed: 38817820
DOI: 10.1016/j.jsps.2024.102110 -
BMC Cancer May 2024Breast and cervical cancer are the two leading cancers in terms of incidence and mortality. Previous studies reported different interleukins, including interleukin-17A...
BACKGROUND
Breast and cervical cancer are the two leading cancers in terms of incidence and mortality. Previous studies reported different interleukins, including interleukin-17A (IL-17A) to be responsible for the development and progression of these malignancies. Therefore, we speculated that the variants in this gene might be associated with these cancer developments in Bangladeshi population. For evaluating the hypothesis, we investigated the association of IL-17A rs3748067 polymorphism with the susceptibility of both breast and cervical cancer.
METHODS
This case-control study was performed on 156 breast cancer patients, 156 cervical cancer patients, and 156 controls using the tetra-primer amplification refractory mutation system-polymerase chain reaction. The statistical software package SPSS (version 25.0) was applied for analyses. The genetic association was measured by the odds ratio (OR) and 95% confidence intervals (CIs). A statistically significant association was considered when p-value ≤ 0.05. Functional analysis was performed using GEPIA and UALCAN databases.
RESULTS
From the calculation of the association of IL-17A rs3748067 with breast cancer, it is found that no genotype or allele showed a statistically significant association (p>0.05). On the other hand, the analysis of IL-17A rs3748067 with cervical cancer demonstrated that CT genotype showed a significant association (CT vs. CC: OR=1.79, p=0.021). In the overdominant model, CT genotype also revealed a statistically significant association with cervical cancer, which is found to be statistically significant (OR=1.84, p=0.015).
CONCLUSION
Our study summarizes that rs3748067 polymorphism in the IL-17A gene may be associated with cervical cancer but not breast cancer in Bangladeshi patients. However, we suggest studies in the future with a larger sample size.
Topics: Humans; Female; Interleukin-17; Breast Neoplasms; Uterine Cervical Neoplasms; Case-Control Studies; Genetic Predisposition to Disease; Bangladesh; Polymorphism, Single Nucleotide; Middle Aged; Adult; Genotype; Genetic Association Studies; Alleles; Odds Ratio; Aged
PubMed: 38816694
DOI: 10.1186/s12885-024-12352-0 -
NPJ Genomic Medicine May 2024Kawasaki disease (KD) is a multisystem inflammatory illness of infants and young children that can result in acute vasculitis. The mechanism of coronary artery aneurysms...
Kawasaki disease (KD) is a multisystem inflammatory illness of infants and young children that can result in acute vasculitis. The mechanism of coronary artery aneurysms (CAA) in KD despite intravenous gamma globulin (IVIG) treatment is not known. We performed a Whole Genome Sequencing (WGS) association analysis in a racially diverse cohort of KD patients treated with IVIG, both using AHA guidelines. We defined coronary aneurysm (CAA) (N = 234) as coronary z ≥ 2.5 and large coronary aneurysm (CAA/L) (N = 92) as z ≥ 5.0. We conducted logistic regression models to examine the association of genetic variants with CAA/L during acute KD and with persistence >6 weeks using an additive model between cases and 238 controls with no CAA. We adjusted for age, gender and three principal components of genetic ancestry. The top significant variants associated with CAA/L were in the intergenic regions (rs62154092 p < 6.32E-08 most significant). Variants in SMAT4, LOC100127, PTPRD, TCAF2 and KLRC2 were the most significant non-intergenic SNPs. Functional mapping and annotation (FUMA) analysis identified 12 genomic risk loci with eQTL or chromatin interactions mapped to 48 genes. Of these NDUFA5 has been implicated in KD CAA and MICU and ZMAT4 has potential functional implications. Genetic risk score using these 12 genomic risk loci yielded an area under the receiver operating characteristic curve (AUC) of 0.86. This pharmacogenomics study provides insights into the pathogenesis of CAA/L in IVIG-treated KD and shows that genomics can help define the cause of CAA/L to guide management and improve risk stratification of KD patients.
PubMed: 38816462
DOI: 10.1038/s41525-024-00419-7 -
NPJ Systems Biology and Applications May 2024Individual may response to drug treatment differently due to their genetic variants located in enhancers. These variants can alter transcription factor's (TF) binding...
Individual may response to drug treatment differently due to their genetic variants located in enhancers. These variants can alter transcription factor's (TF) binding strength, affect enhancer's chromatin activity or interaction, and eventually change expression level of downstream gene. Here, we propose a computational framework, PERD, to Predict the Enhancers Responsive to Drug. A machine learning model was trained to predict the genome-wide chromatin accessibility from transcriptome data using the paired expression and chromatin accessibility data collected from ENCODE and ROADMAP. Then the model was applied to the perturbed gene expression data from Connectivity Map (CMAP) and Cancer Drug-induced gene expression Signature DataBase (CDS-DB) and identify drug responsive enhancers with significantly altered chromatin accessibility. Furthermore, the drug responsive enhancers were related to the pharmacogenomics genome-wide association studies (PGx GWAS). Stepping on the traditional drug-associated gene signatures, PERD holds the promise to enhance the causality of drug perturbation by providing candidate regulatory element of those drug associated genes.
Topics: Chromatin; Humans; Machine Learning; Genome-Wide Association Study; Enhancer Elements, Genetic; Computational Biology; Transcriptome; Transcription Factors; Gene Expression Profiling; Pharmacogenetics
PubMed: 38816426
DOI: 10.1038/s41540-024-00388-8 -
PloS One 2024A web application, GTExome, is described that quickly identifies, classifies, and models missense mutations in commonly expressed human proteins. GTExome can be used to...
A web application, GTExome, is described that quickly identifies, classifies, and models missense mutations in commonly expressed human proteins. GTExome can be used to categorize genomic mutation data with tissue specific expression data from the Genotype-Tissue Expression (GTEx) project. Commonly expressed missense mutations in proteins from a wide range of tissue types can be selected and assessed for modeling suitability. Information about the consequences of each mutation is provided to the user including if disulfide bonds, hydrogen bonds, or salt bridges are broken, buried prolines introduced, buried charges are created or lost, charge is swapped, a buried glycine is replaced, or if the residue that would be removed is a proline in the cis configuration. Also, if the mutation site is in a binding pocket the number of pockets and their volumes are reported. The user can assess this information and then select from available experimental or computationally predicted structures of native proteins to create, visualize, and download a model of the mutated protein using Fast and Accurate Side-chain Protein Repacking (FASPR). For AlphaFold modeled proteins, confidence scores for native proteins are provided. Using this tool, we explored a set of 9,666 common missense mutations from a variety of tissues from GTEx and show that most mutations can be modeled using this tool to facilitate studies of protein-protein and protein-drug interactions. The open-source tool is freely available at https://pharmacogenomics.clas.ucdenver.edu/gtexome/.
Topics: Humans; Mutation, Missense; Genome, Human; Models, Molecular; Software; Internet; Proteins
PubMed: 38814966
DOI: 10.1371/journal.pone.0303604