Assessment Of Sensitivity Research Articles

Causal relationships between plasma lipidome and diabetic neuropathy: a Mendelian randomization study

BackgroundDyslipidemia is closely related to diabetic neuropathy. This study examined the potential causal relationship involving 179 lipid species and the disease.MethodsThe pooled data on 179 lipid species and diabetic neuropathy were obtained from previous genome-wide association studies (GWAS). A Mendelian Randomization (MR) method was employed to investigate the potential causal link, and the robustness of the findings was confirmed through comprehensive sensitivity analyses.ResultsGenetically, phosphatidylcholine might be associated with the risk of diabetic neuropathy. Upon adjusting for multiple comparisons, higher levels of phosphatidylcholine (16:0_20:2) (OR = 0.82, 95%CI: 0.73-0.91; P < 0.001, FDR = 0.033) and phosphatidylcholine (16:1_18:1) (OR = 0.77, 95%CI: 0.67-0.88; P < 0.001, FDR = 0.019) are associated with a decreased risk of diabetic neuropathy. Further multivariable MR (MVMR) analysis demonstrated the effect of genetically predicted phosphatidylcholine (16:1_18:1) remained after adjusting for body mass index (BMI) and glycated hemoglobin (HbA1c). Sensitivity assessments have confirmed the robustness of these findings, revealing no evidence of heterogeneity or pleiotropy.ConclusionOur research linked certain lipid species with diabetic neuropathy risk, suggesting that targeting lipids could be a therapeutic strategy in clinical trials addressing this condition.

Evaluating the Sensitivity of Consumption towards the Price of Components of the Consumer Basket

This study investigates Jordanian market demand in terms of consumption sensitivity to changes in consumer basket component prices. The researchers anticipate that the study, through analysing demand functions and elasticities, will help to add qualitative insights to the Jordanian economic database. The researchers statistically derived coefficients based on information about the consumer basket used to calculate the standard price index using simple linear logarithmic regression. Using this methodology, the research study has produced several findings, including: There are two types of consumer basket components: elastic and inelastic. A strong divide occurs at the level of the consumer basket between critical first-tier goods and second-tier consumer goods. Consumption sensitivity assessments can influence governmental decisions about tax policy as well as businessmen decisions regarding production volume and output capability. The price elasticity of demand for chickpeas, cakes, green olives, black olives, and kerosene is 5%, 17.8%, 6.9%, 3.7%, and 1.2%, respectively.

Sodium, the Vascular Endothelium, and Hypertension: A Narrative Review of Literature.

The vascular endothelium and its endothelial glycocalyx contribute to the protection of the endothelial cells from exposure to high levels of sodium and help these structures maintain normal function by regulating vascular permeability due to its buffering effect. The endothelial glycocalyx has negative surface charges that bind sodium and limit sodium entry into cells and the interstitial space. High sodium levels can disrupt this barrier and allow the movement of sodium into cells and extravascular fluid. This can generate reactive oxygen species that inhibit nitric oxide production. This leads to vasospasm and increases intravascular pressures. Overtime vascular remodeling occurs, and this changes the anatomy of blood vessels, their intrinsic stiffness, and their response to vasodilators and results in hypertension. Patients with increased salt sensitivity are potentially at more risk for this sequence of events. Studies on the degradation of the glycocalyx provide insight into the pathogenesis of clinical disorders with vascular involvement, but there is limited information available in the context of higher concentrations of sodium. Data on higher intake of sodium and the imbalance between nitric oxide and reactive oxygen species have been obtained in experimental studies and provide insights into possible outcomes in humans. The current western diet with sodium intake above recommended levels has led to the assessment of sodium sensitivity, which has been used in different populations and could become a practical tool to evaluate patients. This would potentially allow more focused recommendations regarding salt intake. This review will consider the structure of the vascular endothelium, its components, the effect of sodium on it, and the use of the salt blood test mini.

Associations between environmental glyphosate exposure and glucose homeostasis indices in US general adults: a national population-based cross-sectional study

As glyphosate’s application becomes increasingly widespread across the globe, its potential adverse effects on humans have garnered growing concerns. Little evidence has revealed the associations between glyphosate and glucose homeostasis. A total of 2094 individuals were recruited from the NHANES 2013–2018. Urinary glyphosate, alkaline phosphatase (ALP), fasting plasma glucose (FPG), fasting insulin, and glycated hemoglobin A1c (HbA1c) were measured. Homeostatic model assessment of beta-cell function (HOMA2-β), insulin resistance (HOMA2-IR), and insulin sensitivity (HOMA2-IS) were assessed. Generalized linear models and mediation analyses were fitted to estimate the potential associations between glyphosate, glucose homeostasis, and ALP. Urinary glyphosate demonstrated a statistically significant positive association with FPG and HbA1c in a linear positive dose–response manner, while showing a linear negative association with HOMA2-β. Each doubling increase in urinary glyphosate was associated with a 1.13%, 1.50%, and − 2.80% alteration in FPG, HbA1c, and HOMA2-β, respectively. Obesity modified the association between urinary glyphosate and glucose dyshomeostasis with stronger associations in obese individuals. In addition, elevated ALP significantly mediated the associations of urinary glyphosate with FPG and HbA1c, with mediated proportions of 9.91% and 20.23%, respectively. Environmental glyphosate exposure was associated with glucose dyshomeostasis, which was more pronounced in obese individuals and was partly mediated by ALP.

Institutional experience with implanted cardiac device risk level assessment: Comparing calculation and measurement.

The use of in-vivo dosimetry is a long-standing but also labor-intensive component of risk-level assessment for patients with implanted devices. A calculation-only approach, using treatment planning system (TPS)-calculated doses along with imaging doses estimates when relevant, has the potential to streamline the physics workflow without negatively impacting patient safety. To evaluate the feasibility of using a calculation-only approach for risk level assessment for patients with implanted electronic medical devices. A total of 86 patients were included in this retrospective study. For each patient, in-vivo dosimetry measurements using optically stimulated luminescent dosimeter (OSLD) were compared to calculated doses (based on TPS calculated doses and an estimate of imaging doses when relevant). The comparison of OSLD doses and estimated predicted doses was structured in the following manner: (1) direct comparison of both absolute dose difference and percent difference for measured and calculated doses, (2) risk level assessment comparison using measured and estimated doses, and (3) sensitivity and positive predictive value assessment of each method for TG-203 risk level assessment. For all cases, the calculation-based approach yielded a risk level that was equivalent to or more conservative than the risk level from OSLD measurement. For 79 of 86 patients (91.9%), the calculated and measured doses provided the same risk level. For 7 of 86 patients (8.1%), the calculated dose yielded the more conservative risk level. The calculation-based dose estimate provided a sensitivity of 1.00 with a positive predictive value of 0.92. The use of a calculation-only approach has the potential to reduce workload while maintaining the efficacy of risk-level assessment for patients with implanted devices.

Causal Association between Arm Fat, Left Leg Fat, and Trunk Fat Masses and Risk of Polycystic Ovarian Syndrome: A Mendelian Randomization Study.

Observational studies have reported that arm fat, left leg fat, and trunk fat masses have different effects on polycystic ovarian syndrome (PCOS). However, the causal relationship between them remains unknown. A two-sample Mendelian randomization (MR) study was conducted by utilizing pooled data from the largest Genome-Wide Association Study (GWAS). Random effect inverse variance weighted (IVW) method, weighted median (WM), and MR-Egger regression analysis were the main statistical methods utilized. Finally, a sensitivity assessment was conducted. Cochran's Q test was used to analyze heterogeneity, whereas MR-Egger regression (intercept term) was used to analyze horizontal pleiotropy. The leave-one-out analysis was performed to assess if MR estimates were impacted by a single nucleotide polymorphism (SNP) exhibiting significant horizontal pleiotropy. This study discovered a significant positive correlation between left leg fat mass, arm fat mass, and trunk fat mass and genetic factors of PCOS (odds ratio (OR): 4.452, confidence interval (CI): 2.740-7.232, p < 0.001, OR: 3.321, CI: 2.248-4.907, p < 0.001, and OR: 2.518, CI: 1.722-3.682, p < 0.001, respectively). This study indicates that arm fat, left leg fat, and trunk fat masses may be genetically correlated with PCOS.

Impact of signal-to-noise ratio and contrast definition on the sensitivity assessment and benchmarking of fluorescence molecular imaging systems.

Standardization of fluorescence molecular imaging (FMI) is critical for ensuring quality control in guiding surgical procedures. To accurately evaluate system performance, two metrics, the signal-to-noise ratio (SNR) and contrast, are widely employed. However, there is currently no consensus on how these metrics can be computed. We aim to examine the impact of SNR and contrast definitions on the performance assessment of FMI systems. We quantified the SNR and contrast of six near-infrared FMI systems by imaging a multi-parametric phantom. Based on approaches commonly used in the literature, we quantified seven SNRs and four contrast values considering different background regions and/or formulas. Then, we calculated benchmarking (BM) scores and respective rank values for each system. We show that the performance assessment of an FMI system changes depending on the background locations and the applied quantification method. For a single system, the different metrics can vary up to (SNR), . (contrast), and . (BM score). The definition of precise guidelines for FMI performance assessment is imperative to ensure successful clinical translation of the technology. Such guidelines can also enable quality control for the already clinically approved indocyanine green-based fluorescence image-guided surgery.

THREE-DIMENSIONAL HILL OF VISION OF RETINAL SENSITIVITY IN PARTICIPANTS WITH X-LINKED RETINITIS PIGMENTOSA UNDER SCOTOPIC AND MESOPIC CONDITIONS.

To evaluate the utility of three-dimensional hill of vision (HOV) analysis in assessing retinal sensitivity in patients with X-linked retinitis pigmentosa (XLRP) under scotopic cyan, scotopic red, and mesopic microperimetry conditions. Baseline microperimetry data from 31 eyes of 16 patients with XLRP enrolled in the Horizon study were analyzed. HOVs were generated using thin plate spline interpolation. Grid volumes of the central 20° (V 20 ) were compared between lighting conditions using the Wilcoxon signed-rank test with Bonferroni correction. Central and global deficits were evaluated across age groups and genotypes. The mesopic group showed the highest mean V 20 (1.3 dB-Sr), followed by scotopic red (0.6 dB-Sr) and scotopic cyan (0.5 dB-Sr). Significant differences were found between mesopic and scotopic conditions (P < 0.01), but not between scotopic conditions ( P = 0.26). Central and global deficits were more prevalent under scotopic conditions and increased with age. HOV analysis provides a comprehensive assessment of retinal sensitivity in XLRP, enabling detection of localized changes and quantification of sensitivity gradients. This volumetric approach offers advantages over traditional methods for diagnosis, monitoring progression, and evaluating treatment response.

Assessment of Antibiotic Sensitivity of Pseudomonas aeruginosa Isolated from Different Clinical Samples

Assessment of Antibiotic Sensitivity of Pseudomonas aeruginosa Isolated from Different Clinical Samples

Sensitivity Assessment of Atmospheric Corrections for Clear and Moderately Turbid Optical Waters

Sensitivity Assessment of Atmospheric Corrections for Clear and Moderately Turbid Optical Waters

Assessment of dermal sensitization by nickel salts in a novel humanized TLR-4 mouse model

The fundamental goal of this study was to determine the potential utility of a novel humanized Toll-like receptor-4 (hTLR-4) mouse model for future in vivo studies of nickel allergy. First, mice of both sexes and hTLR-4 expression profiles were incorporated into a Local Lymph Node Assay (LLNA) to assess skin sensitization. Next, a set of hTLR-4 hTLR-4-positive mice (female and male groups) was similarly exposed to vehicle control (VC) or 10% NiSO4 on Days 1, 2, and 3. Mice were euthanized on Day 10, lymph node (LN) cellularity was assessed, LN and spleen cells were phenotyped, and serum was collected to quantify circulating cytokine and IgE levels. In the LLNA, hTLR-4-positive mice of both sexes exhibited enhanced responsivity to nickel. NiSO4 (10%) had a stimulation index (SI) of 3.7 (females) and 3.8 (males) in hTLR-4-positive animals, and an SI of 0.5 (females) and 0.8 (males) in hTLR-4 hTLR-4-negative mice. In the 10d study, hTLR-4-positive mice exposed to 10% NiSO4 exhibited increased LN cellularity (6.0× increase in females, 3.2× in males) and significantly higher concentrations of circulating IgE (4.1× increase in females, 3.4× in males). Significant increases in serum interferon (IFN)-γ, interleukin (IL)-4, and IL-5 levels were seen in female mice, while altered concentrations of IL-4 and IL-10 were detected in male mice. The results of this study ultimately demonstrate that murine expression of hTLR-4 confers enhanced susceptibility to dermal sensitization by nickel, and consequently, the hTLR-4 mouse model represents a viable approach for future studies of nickel allergy in vivo.

Adsorption and Sensing Performance of Transition Metal Decorated Graphene Quantum Dots for AsH3, NH3, PH3, and H2S.

We have conducted a systematic study employing density functional theory (DFT) and quantum theory of atoms in molecules (QTAIM) to explore the gas sensing capabilities of nitrogen-doped single vacancy graphene quantum dots (SV/3N) decorated with transition metals (TM = Mn, Co, Cu). We have studied the interactions between TM@SV/3N and four different target gases (AsH3, NH3, PH3, and H2S) through the computation of adsorption energies, charge transfer, noncovalent interaction, density of states, band gap, and work function for 12 distinct adsorption systems. Our comprehensive analysis included an in-depth assessment of sensors' stability, sensitivity, selectivity, and reusability for practical applications. Our findings indicate that the Co@SV/3N surface strongly interacts with PH3, with the highest adsorption energy (-1.15 eV). It shows remarkable sensitivity and selectivity toward PH3, making it a promising candidate for PH3 gas sensing applications. Similarly, Mn@SV/3N exhibits high sensitivity and selectivity toward NH3, positioning it as a suitable candidate for NH3 gas sensing applications. We believe this study will provide valuable theoretical guidance for developing TM@SV/3N-based gas sensors.

The Sound Sensitivity Symptoms Questionnaire Version 2.0 (SSSQ2) as a Screening Tool for Assessment of Hyperacusis, Misophonia and Noise Sensitivity: Factor Analysis, Validity, Reliability, and Minimum Detectable Change

Background/Objectives: The Sound Sensitivity Symptoms Questionnaire version 2 (SSSQ2) is a brief clinical tool with six items designed to be used (1) as a measure for severity of sound sensitivity symptoms in general (based on its total score) and (2) as a checklist to screen different forms of sound sensitivity. The objective of this study was to assess the psychometric properties of the SSSQ2. Method: This was a cross-sectional study. A total of 451 people completed the online survey. A total of 154 people completed the survey twice with a two-week interval to establish test–retest reliability. The average age of the participants was 36.5 years (range 18 to 86 years). Results: Confirmatory factor analysis showed that the SSSQ2 is a one-factor questionnaire. Cronbach’s α was 0.80. The test–retest reliability was good for the total SSSQ2 score and was moderate for the sum of items 1 and 3 (indicating loudness hyperacusis), item 2 (for pain hyperacusis), item 4 (for misophonia), item 5 (for fear hyperacusis), and item 6 (for noise sensitivity). The minimum amount of change that constitutes a true change in the total SSSQ2 score is ≥5 points. Conclusions: The SSSQ2 can be used in clinical practice or research setting to measure the severity of general sound sensitivity as a one-factor questionnaire with acceptable internal consistency and good reliability. In addition, the individual items in the SSSQ2 can be used as a checklist to screen for various forms of sound sensitivity.

Normative prospective data on automatically quantified retinal morphology correlated to retinal function in healthy ageing eyes by two microperimetry devices.

The relationship between retinal morphology, as assessed by optical coherence tomography (OCT), and retinal function in microperimetry (MP) has not been well studied, despite its increasing importance as an essential functional endpoint for clinical trials and emerging therapies in retinal diseases. Normative databases of healthy ageing eyes are largely missing from literature. Healthy subjects above 50 years were examined using two MP devices, MP-3 (NIDEK) and MAIA (iCare). An identical grid, encompassing 45 stimuli was used for retinal sensitivity (RS) assessment. Deep-learning-based algorithms performed automated segmentation of ellipsoid zone (EZ), outer nuclear layer (ONL), ganglion cell layer (GCL) and retinal nerve fibre layer (RNFL) from OCT volumes (Spectralis, Heidelberg). Pointwise co-registration between each MP stimulus and corresponding location on OCT was performed via registration algorithm. Effect of age, eccentricity and layer thickness on RS was assessed by mixed effect models. Three thousand six hundred stimuli from twenty eyes of twenty patients were included. Mean patient age was 68.9 ± 10.9 years. Mean RS for the first exam was 28.65 ± 2.49 dB and 25.5 ± 2.81 dB for MP-3 and MAIA, respectively. Increased EZ thickness, ONL thickness and GCL thickness were significantly correlated with increased RS (all p < 0.001). Univariate models showed lower RS with advanced age and higher eccentricity (both p < 0.05). This work provides reference values for healthy age-related EZ and ONL-thicknesses without impairment of visual function and evidence for RS decrease with eccentricity and increasing age. This information is crucial for interpretation of future clinical trials in disease.

Современное состояние проблемы высокофункционального аутизма

&lt;p style="text-align: justify;"&gt;&lt;strong&gt;Objective.&lt;/strong&gt; Among autism spectrum disorders (ASD), high functional autism (HFA) is not considered a separate nosological entity. However, a number of foreign studies have shown that 10% of people with ASD are diagnosed with HFA. We discuss the characteristics of HFA as well as its differences from other ASD subgroups. The article also summarizes the current state of research on the HFA issue. A clearer understanding of both psychology and neurophysiology of high-functioning autism will help ensure accurate diagnosis, avoiding errors in therapy planning and support.&lt;/p&gt; &lt;p style="text-align: justify;"&gt;&lt;strong&gt;Methods.&lt;/strong&gt; We reviewed literature sources in the PubMed, MedLine, and Scientific Electronic Library databases. The main search terms were: high-functioning autism, HFA, Asperger&amp;rsquo;s syndrome, autism spectrum disorders (ASD), diagnosis and speech disorders. Forty-two articles by foreign and domestic specialists were included in the analysis.&lt;/p&gt; &lt;p style="text-align: justify;"&gt;&lt;strong&gt;Results.&lt;/strong&gt; The developmental profile of individuals with high-functioning autism differs from that of individuals with autism and cognitive or speech impairments. It is characterized by a distinctive style of social interaction and a higher level of speech and cognitive development. A high level of intelligence helps people with HFA master social rules and adapt more effectively.&lt;/p&gt; &lt;p style="text-align: justify;"&gt;&lt;strong&gt;Conclusions.&lt;/strong&gt; Social impairments in individuals with high-functioning autism are difficult to identify in early childhood, partly due to the lack of developed diagnostic tools. Therefore, there is a need for more careful assessment of children suspected of having high-functioning autism, as well as the development of reliable, sensitive assessment tools for follow-up therapy and support.&lt;/p&gt;

Pan‐Cancer Analysis of Ezrin: A Comprehensive Examination of Its Prognostic Value and Immunological Implications

ABSTRACTBackgroundEzrin, a member of the ERM protein family, has emerged as a pivotal player in the progression of diverse tumor types and exhibits substantial immunomodulatory capabilities in inflammatory disorders and tumor‐associated immune reactions. Studies have validated the antitumor efficacy of ezrin inhibitors. However, a comprehensive pan‐cancer analysis to fully elucidate the functional implications of ezrin has not been performed.MethodsHerein, we performed a multifaceted database investigation to evaluate ezrin expression patterns in relation to clinical outcomes, immune checkpoint modulators, prognostic indicators, genomic profiles, and immunological features.ResultsOur analysis revealed distinct ezrin expression patterns across various cancers, with a pronounced association between ezrin expression and immune cell infiltration. Furthermore, drug sensitivity assessments using the GDSC and CTRP databases underscored a robust correlation between ezrin expression and responsiveness to anticancer agents, highlighting its potential as a therapeutic target. Notably, ezrin expression also correlated with patient survival outcomes in the context of anti‐PD1 therapy treatment, suggesting its potential role as a predictive biomarker for immune checkpoint blockade therapies.ConclusionOur results indicate ezrin as a promising immunomodulatory target and a valuable diagnostic and prognostic marker for select cancer types. However, the intricate mechanisms underlying ezrin involvement in tumor immune responses necessitate further in‐depth investigation to fully harness its therapeutic and prognostic potential.

Features of contrast sensitivity in patients with age-related cataracts

аge-related cataracts are a common ophthalmological condition characterised by clouding of the lens of the eye. This leads to reduced visual acuity, blurred images, and impaired colour perception. To assess the need for cataract surgery, it is important to evaluate contrast sensitivity, which shows a person's ability to distinguish small details that differ in brightness. The development of accurate and effective methods for the diagnosis and treatment of cataracts is an urgent scientific and practical problem. The aim of the study is to determine the diagnostic value of contrast sensitivity in patients with age-related cataracts by comparing two methods of its study. The study was conducted at the Department of Ophthalmology of the Bogomolets National Medical University on the basis of St. Michael's Clinical Hospital in Kyiv and the Medical Ophthalmological Centre ‘Zir 100%’. The study included 100 patients (100 eyes) aged 45 to 75 years diagnosed with age-related cataracts and undergoing phacoemulsification surgery with IOL implantation. The study involved 55 women and 45 men. Patients were divided into 2 groups: Group 1 - 50 patients (50 eyes) who underwent contrast sensitivity measurement using the Pelli-Robson table, Group 2 - 50 patients (50 eyes) who underwent Clinic CSF Contrast Sensitivity test. To participate in the study, all participants had to sign an informed consent. Measurements were performed 1 day before surgery and 7 days and 1 month after surgery. According to the results of the study, the comparison of contrast sensitivity between men and women did not reveal a statistically significant difference when using both methods (p=0.5). This indicates that gender is not a determining factor in the change in contrast sensitivity within the study sample. Regardless of the method of measurement, the average values of contrast sensitivity in men and women are similar, which confirms the absence of sex dependence in the functional results of the visual system by this parameter. The analysis of the results of the two methods of measuring contrast sensitivity showed that the Clinic CSF Contrast Sensitivity test demonstrates statistically higher results compared to the Pelli-Robson table (p value &lt; 0.05). This may be due to the more accurate and sensitive measurement methods used in digital devices, which can better reflect subtle changes in contrast sensitivity. Therefore, the Clinic CSF Contrast Sensitivity test may provide a more sensitive assessment of contrast sensitivity, making it a more effective tool in clinical practice for assessing functional vision.

Evaluating the Reliability of a Microperimetry-Based Method for Assessing Visual Function in the Junctional Zone of Geographic Atrophy Lesions.

To assess the repeatability of a microperimetry methodology for quantifying visual function changes in the junctional zone of eyes with geographic atrophy (GA) in the clinical trial context. A post hoc analysis of the OAKS phase III trial was conducted, which enrolled patients with GA secondary to age-related macular degeneration. Microperimetry using a standard 10-2 fovea centered grid was performed at baseline and follow-up visits. GA regions were traced on fundus autofluorescence (FAF) images. Two graders independently registered baseline microperimetry images with baseline FAF images in a sampling of 30 eyes from the OAKS study. Agreement between the two graders' assessments of mean sensitivity and the number of scotomatous points within a ±250 μm GA junctional zone was assessed. The intraclass correlation (ICC) and coefficient of repeatability (CoR) for the mean junctional zone sensitivity were 0.994 and 0.349 dB, respectively. The ICC and CoR for the total number of scotomatous points within the junctional zone were 0.997 and 0.218, respectively. The repeatability of the methodology and its compatibility with standard MP acquisitions appear to make it well-suited for identifying and analyzing retinal sensitivity within high-risk areas of the retina.

An Integrated Testing Strategy and Online Tool for Assessing Skin Sensitization of Agrochemical Formulations.

Non-animal assessment of skin sensitization is a global trend. Recently, scientific efforts have been focused on the integration of multiple evidence for decision making with the publication of OECD Guideline No. 497 for defined approaches to skin sensitization. The integrated testing strategy (ITS) methods reported by the guideline integrates in chemico, in vitro, and in silico testing to assess both hazard and potency of skin sensitization. The incorporation of in silico methods achieved comparable performance with fewer experiments compared to the traditional two-out-of-three (2o3) method. However, the direct application of current ITSs to agrochemicals can be problematic due to the lack of agrochemicals in the training data of the incorporated in silico methods. To address the issue, we present ITS-SkinSensPred 2.0 for agrochemicals and agrochemical formulations using a reconfigured in silico model SkinSensPred for pesticides. Compared to ITSv2, the proposed ITS-SkinSensPred 2.0 achieved an 11% and 16% improvement in the accuracy and correct classification rate for hazard identification and potency classification, respectively. In addition, an online ITS tool was implemented and available on the SkinSensDB website. The tool is expected to be useful for evaluating skin sensitization of substances.

Development of RT h-CLAT, a Rapid Assessment Method for Skin Sensitizers Using THP-1 Cells as a Biosensor.

In recent years, in vitro skin sensitization assays have been recommended as animal-free alternatives for the safety assessment of cosmetics and topical drugs, and these methods have been adopted in OECD test guidelines. However, existing assays remain complex and costly. To address this, we recently developed a more efficient, cost-effective, and accurate method for evaluating skin sensitizers by using immune cell-derived THP-1 cells as a biosensor, coupled with an RT-PCR-based assay. In this study, we further refined this method to enable even faster assessment of skin sensitization. By performing comprehensive RNA sequencing (RNA-Seq) analysis, we examined gene expression profiles induced by sensitizers in THP-1 cells to identify potential sensitization markers, ultimately selecting the optimal markers and conditions for evaluation. Our findings indicate that after exposing a test chemical to THP-1 cells for 5 h, measuring the expression levels of the JUN and HMOX1 genes via real-time PCR allows for a reliable assessment of sensitization. A test compound is defined as a sensitizer if either gene shows a more than two-fold increase in its expression compared to the control. Applying this improved method, designated as RT h-CLAT, we evaluated the sensitization potential of 43 chemicals. The results demonstrated higher accuracy compared to the human cell line activation test (h-CLAT) listed in the OECD guidelines, while also reducing the required assessment time from two days to one.