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Results for “Experimental validation”

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At least 73 records · Page 4Linked to original sources
PubMed2026

Multi-Omics Integration Identifies a Five-Gene Metabolic Signature With Experimental Validation in Clear Cell Renal Cell Carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is hallmarked by profound metabolic reprogramming; however, its intricate crosstalk with the tumor immune microenvironment (TIME) and its clinical ramifications remain inadequately elucidated. This study aims to systematically decipher the metabolic-immune interplay in ccRCC through multi-omics integration, with the goal of identifying robust prognostic biomarkers and actionable therapeutic vulnerabilities. AIMS: This study aims to systematically decipher the metabolic-immune interplay in clear cell renal cell carcinoma (ccRCC) through multi‑omics integration, and to identify robust prognostic biomarkers and actionable therapeutic vulnerabilities that can inform precision risk stratification and individualized treatment strategies. METHODS: We integrated bulk transcriptomic, genomic, and clinical data from multiple ccRCC cohorts. Differential expression and functional enrichment analyses were performed to characterize metabolic pathway alterations. Mendelian randomization (MR) was employed to infer causal relationships between metabolic disorders and ccRCC risk. A machine learning-based prognostic framework, incorporating SHAP (SHapley Additive exPlanations) for feature interpretability, was constructed and rigorously validated. TIME heterogeneity was dissected using deconvolution algorithms, while drug sensitivity, tumor mutation burden (TMB), and TIDE scores were utilized to assess therapeutic responses and immune evasion. Candidate gene function was evaluated through in vitro gain- and loss-of-function assays, with expression validated via TCGA, HPA, western blot, and qRT-PCR. RESULTS: Enrichment analysis identified coordinated dysregulation in lipid metabolism, energy homeostasis, and hypoxia response pathways. MR analysis confirmed lipid metabolism disorders as a causal risk factor for ccRCC. Our machine-learning model, centered on five core SHAP-identified features (SUCLA2, ACAT1, PC, SUCLG1, and HMGCS2), demonstrated superior predictive accuracy over conventional clinical staging. Immune profiling unveiled dichotomous TIME states: the low-risk group retained active immune surveillance, whereas the high-risk group was enriched with immunosuppressive subsets. Drug sensitivity screening pinpointed LY2109761 and carmustine as high-risk-specific candidate agents. Furthermore, TMB and TIDE analyses stratified high-risk patients displaying genomic instability and immune evasion phenotypes. Functionally, SUCLA2 knockdown significantly enhanced ccRCC cell proliferation and invasion, while its overexpression suppressed these malignant phenotypes, corroborating its tumor-suppressive role. Expression patterns of the hub genes were consistently validated across multi-level datasets and experimental assays. CONCLUSION: This study establishes a precision oncology framework for ccRCC by functionally linking metabolic biomarkers, immunophenotypes, and stratified therapeutic strategies. Importantly, we identify SUCLA2 as a potential functional tumor suppressor and a promising target for further mechanistic and translational investigation.

Humans↗
PubMed2006

An efficient and high-throughput approach for experimental validation of novel human gene predictions.

A highly automated RT-PCR-based approach has been established to validate novel human gene predictions with no prior experimental evidence of mRNA splicing (ab initio predictions). Ab initio gene predictions were selected for high-throughput validation using predicted protein classification, sequence similarity to other genomes, colocalization with an MPSS tag, or microarray expression. Initial microarray prioritization followed by RT-PCR validation was the most efficient combination, resulting in approximately 35% of the ab initio predictions being validated by RT-PCR. Of the 7252 novel genes that were prioritized and processed, 796 constituted real transcripts. In addition, high-throughput RACE successfully extended the 5' and/or 3' ends of >60% of RT-PCR-validated genes. Reevaluation of these transcripts produced 574 novel transcripts using RefSeq as a reference. RT-PCR sequencing in combination with RACE on ab initio gene predictions could be used to define the transcriptome across all species.

Algorithms↗
PubMedDate not supplied

[The clinico-experimental validation of the use of low-intensity laser radiation for the treatment of exacerbated recurrent herpetic stomatitis in children].

Experimental data are presented, validating the use of low-intensity laser irradiation at a wave length of 633 nm for the treatment of chronic recurrent herpetic stomatitis. Clinical trials were carried out in 167 children. Laser exposure with the optimal stimulating parameters was found to be an effective means for the treatment of children suffering from this condition.

Adenosine Triphosphate↗
PubMed2004

A three-dimensional finite element model of the human anterior cruciate ligament: a computational analysis with experimental validation.

In this study, the force and stress distribution within the anteromedial (AM) and posterolateral (PL) bundles of the anterior cruciate ligament (ACL) in response to an anterior tibial load with the knee at full extension was calculated using a validated three-dimensional finite element model (FEM) of a human ACL. The interaction between the AM and PL bundles, as well as the contact and friction caused by the ACL wrapping around the bone during knee motion, were included in the model. The AM and PL bundles of the ACL were simulated as incompressible homogeneous and isotropic hyperelastic materials. The multiple-degrees-of-freedom (DOF) knee kinematics of a cadaveric knee were first obtained using a robotic/universal force-moment sensor testing system. These data were used as the boundary conditions for the FEM of the ACL to calculate the forces in the ACL. The calculated forces were compared to the in situ force in the ACL, determined experimentally, to validate the model. The validated FEM was then used to calculate the force and stress distribution within the ACL under an anterior tibial load at full extension. The AM and PL bundles shared the force, and the stress distribution was non-uniform within both bundles with the highest stress localized near the femoral insertion site. The contact and friction caused by the ACL wrapping around the bone during knee motion played the role of transferring the force from the ACL to the bone, and had a direct effect on the force and stress distribution of the ACL. This validated model will enable the analysis of force and stress distribution in the ACL in response to more complex loading conditions and has the potential to help design improved surgical procedures following ACL injuries.

Anterior Cruciate Ligament↗
PubMed2026

Network pharmacology-based prediction and experimental validation of the anti-hyperuricemic effects of oolong tea polyphenols.

OBJECTIVE: This study aimed to identify candidate therapeutic targets of oolong tea polyphenols (TP) against hyperuricemia (HUA) using network pharmacology and bioinformatics, and to validate the predicted molecular mechanism through in vivo experimentation. METHODS: Drug and disease targets were retrieved from public databases, and overlapping targets were identified by Venn diagram analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the shared targets, and a protein-protein interaction (PPI) network was constructed to identify hub genes. For in vivo validation, an HUA mouse model was established by 15 days of oral potassium oxonate (PO) administration. Model mice then received TP by gavage at low (0.5 g⋅kg-1⋅d-1), medium (1 g⋅kg-1⋅d-1), or high (2 g⋅kg-1⋅d-1) doses for an additional 15 days. Serum biochemical markers, histopathological changes, and pathway-related protein expression were assessed by enzyme-linked immunosorbent assay (ELISA), hematoxylin and eosin (HE) staining, and western blot analysis, respectively. RESULTS: Network pharmacology analysis identified 59 overlapping targets between TP and HUA; GO and KEGG enrichment analyses revealed that these targets were primarily associated with hormone metabolism and the PI3K-AKT signaling pathway. In the animal experiment, TP dose-dependently reduced serum uric acid (SUA) levels in hyperuricemic mice. At the molecular level, low and medium doses of TP suppressed phosphorylation of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR), whereas the high dose paradoxically activated this pathway and concomitantly elevated interleukin-1β levels. These findings indicate that TP modulates uric acid metabolism through a non-monotonic, dose-dependent mechanism. CONCLUSION: By combining network pharmacology with animal experiments, this study identified the PI3K/AKT/mTOR signaling pathway as a likely mediator of the anti-hyperuricemic action of oolong tea polyphenols (TP). A medium dose of TP achieved the most balanced outcome, attenuating inflammation and preserving hepatic and renal architecture; the high dose, by contrast, paradoxically elevated interleukin-1β (IL-1β) and overactivated PI3K/AKT/mTOR signaling, underscoring the importance of dose calibration. These data suggest that a medium dose of TP may represent a feasible dietary strategy against hyperuricemia. Further work-including monomer identification, direct target validation, and clinical evaluation-is warranted to confirm and extend these preclinical findings.

PI3K/Akt/mTOR signaling pathway↗
PubMed1983

Noninvasive intraoperative assessment of arterial reconstruction. Experimental validation of the role of central and regional hemodynamics.

We developed an experimental model of graded arterial stenosis to emulate conditions that might be encountered immediately following arterial grafting. Noninvasive measurements of systolic BP and limb blood flow were recorded with a Doppler probe and segmental air plethysmography, respectively, under conditions of different cardiac output and local arterial resistance. These measurements were correlated with direct intra-arterial pressure recordings and flow measurements taken with an electromagnetic flowmeter. There was an excellent correlation between noninvasive and intra-arterial measurements of systolic pressure over a range of cardiac outputs and degree of arterial stenosis. Pulse volume recordings correlated with direct measurements of blood flow at high and baseline cardiac outputs, but the calibration of pulse volume amplitude varied between cuff applications in this canine model. Noninvasive intraoperative monitoring techniques can faithfully represent known physiologic responses to graded arterial stenoses, irrespective of a high cardiac output or peripheral vasodilation.

Animals↗
PubMed2006

The folding pathway of spectrin R17 from experiment and simulation: using experimentally validated MD simulations to characterize States hinted at by experiment.

We present an experimental and computational analysis of the folding pathway of the 17th domain of chicken brain alpha-spectrin, R17. Wild-type R17 folds in a two-state manner and the chevron plot (plot of the logarithm of the observed rate constant against concentration of urea) shows essentially linear folding and unfolding arms. A number of mutant proteins, however, show a change in slope of the unfolding arm at high concentration of denaturant, hinting at complexity in the folding landscape. Through a combination of mutational studies and high temperature molecular dynamics simulations we show that the folding of R17 can be described by a model with two sequential transition states separated by an intermediate species. The rate limiting transition state for folding in water has been characterized both through experimental Phi-value analysis and by simulation. In contrast, a detailed analysis of the transition state predicted to dominate under highly denaturing conditions is only possible by simulation.

Amino Acid Sequence↗
PubMedDate not supplied

A valid experimental brain death organ donor model.

BACKGROUND: This study was designed to establish a validated canine brain death model. Ten consecutive dogs were studied to investigate the effects of brain death on hemodynamic, metabolic, and hormonal function. METHODS: Brain death was induced by inflation of a subdurally placed balloon and was validated neuropathologically. Functional data and blood samples were collected before and 15, 45, 90, 240, 360, and 420 minutes after the induction of brain death. No inotropic or vasoactive support was given. The results are expressed as mean +/- standard error of the mean. RESULTS: The Cushing reflex occurred in all animals and lasted 13.3 +/- 1.5 minutes. Raised catecholamine levels were documented at 15 minutes, whereas the pituitary gland hormones vasopressin and adrenocorticotrophic hormone decreased significantly after 15 and 45 minutes, respectively. Triiodothyronine, thyroxine, and glucagon decreased significantly from 0.58 +/- 0.05 ng/ml, 2.20 +/- 0.15 micrograms/dl, and 49.7 +/- 9.1 pg/ml to 0.34 +/- 0.03 ng/ml (p < 0.05 versus baseline; paired two-tailed t-test), 1.14 +/- 1.14 micrograms/dl (p < 0.05), and 6.9 +/- 1.4 pg/ml (p < 0.05). Insulin and lactate dehydrogenase showed a moderate increase after brain death. Diabetes insipidus occurred after 45 minutes in nine animals (urine output 13.5 +/- 1.8 ml/kg/hour). Left and right ventricular end-diastolic pressure increased significantly toward the end of all experiments. Cardiac output increased and systemic and pulmonary vascular resistance decreased, but heart rate remained unchanged. CONCLUSION: This simple, reproducible, moderately invasive, and reliable model of brain death in animals assesses donor organ function and preservation. Cushing reflex, hyperdynamic state, catecholamine storm, vasopressin and adrenocorticotropic hormone cessation, total cerebral necrosis, and diabetes insipidus were consistent findings.

Acidosis↗
PubMed1989

Computer simulation and experimental validation of the electrophoretic behavior of proteins.

A mathematical model of the electrophoretic behavior of proteins is presented. The Debye-Hückel-Henry theory is used for the description of protein mobility, which has the important result of making net mobility a function of ionic strength. A net charge vs pH relationship and a diffusion coefficient are required to describe a specific protein. The model is employed for the computer simulation of three distinct electrophoretic modes: isoelectric focusing, isotachophoresis, and zone electrophoresis. The validity of the model is tested by comparing simulation with experimental data. Excellent qualitative agreement was found.

Computer Simulation↗
PubMed2001

Threonine requirements of broiler chickens: an experimental validation of a model using growth responses and carcase analysis.

1. This paper describes the experimental testing of a model derived from an analysis of published data on the threonine requirements of broiler chickens. The model, published in a separate paper, showed that the age of the bird and dietary crude protein were highly significant determinants of threonine requirements. 2. We tested this model by measuring the threonine requirements of male broilers aged 7 to 21 d and 21 to 42 d fed on wheat-peanut meal diets containing graded concentrations of threonine. The growth of those birds given adequate threonine was compared with that of others fed a typical wheat-soyabean diet to measure the relative value of peanut meal as a protein concentrate. Finally, we measured the dry matter, nitrogen and fat concentrations in the carcase using near infrared reflectance spectroscopy (NIRS) to test the hypothesis that birds given diets deficient in an amino acid produce carcases with more fat. 3. Increasing the threonine concentration of the diet from 5.7 to 7.2 g/kg improved the growth and feed conversion ratio (FCR) of broilers. However, a further increase in dietary threonine to 7.7 g/kg had an adverse effect. The determined threonine requirement agreed with our prediction model. 4. From 7 to 21 d birds given the diet containing 7.2 g/kg threonine ate more, weighed more, had an improved FCR and, in absolute terms, had carcases with more dry matter, fat and protein than did birds given the wheat-soyabean diet. However, after correction for treatment differences in body mass there were no differences in the carcase parameters. Likewise, there were no differences in any measurements between birds given these two diets between 21 and 42 d.

Age Factors↗
PubMed1986

Quantification of myocardial infarct size by thallium-201 single-photon emission computed tomography: experimental validation in the dog.

To evaluate the potential advantages of thallium-201 (201T1) single-photon emission computerized tomography (SPECT) to assess myocardial infarct size in the experimental animal, six normal dogs and 14 dogs with 6 to 8 hr closed-chest coronary occlusion (eight left anterior descending and six left circumflex) were studied. Ten minutes after intravenous administration of 2 mCi of 201T1, 30 projections were obtained over 180 degrees. The dogs were killed and their hearts sliced and stained by triphenyl tetrazolium chloride (TTC). Pathologic infarct size was calculated for each slice and for the entire left ventricular myocardium as percent weight. Tomograms were quantified by automatically generating maximum-count circumferential profiles, which were compared with normal limit profiles derived from the six normal dogs. Tomographic infarct size was defined as the percentage of circumferential points falling below normal for each tomogram. SPECT and TTC infarct size on 71 slices correlated highly (mean +/- SD 27.9 +/- 23.4% and 26.7 +/- 25.3%, respectively; r = .93, p less than .001, SEE = 9.4%). To determine SPECT infarct size as percent total left ventricular myocardial weight, infarct sizes from each slice were added to one another after each was multiplied by a coefficient that reflected the contribution of that slice to the total left ventricular weight. SPECT and TTC infarct size for the entire left ventricle correlated closely (mean +/- SD 20.5 +/- 7.6% and 19.3 +/- 8.3%, respectively; r = .86, p less than .001, SEE = 4.5%). It is concluded that 201T1 SPECT is a valid method for the noninvasive assessment of experimental myocardial infarct size.

Animals↗
PubMed2004

3-D simulation of the St. Jude Medical bileaflet valve opening process: fluid-structure interaction study and experimental validation.

BACKGROUND AND AIM OF THE STUDY: Simulation of the opening and closure dynamics of a mechanical valve through a moving deforming mesh algorithm presents a challenge because of the large rotations of the leaflet and of the small gaps between the housing and the leaflets, which make remeshing a critical issue. The present study offers a computational approach to the simulation of valve leaflet motion during the opening process, together with an experimental set-up for validation of the model. METHODS: A fully 3-D simulation of the 27 mm St. Jude Medical Hemodynamic Plus mechanical valve was performed using the computational code, Fluent. Interaction between the leaflet and fluid was simulated through customized user subroutines which, according to a weakly coupled approach, update the leaflet velocities through subsequent time steps by means of an under-relaxation procedure. A parallel, experimental test was defined to collect data for the set-up of simulations and for validation purposes. RESULTS: The computed leaflet velocity and angular displacement compared well with experimental data. The model captured the main features of the opening process, and did so also from a quantitative viewpoint. Nonetheless, some discrepancies were observed, including a delay of approximately 7 ms in the computed leaflet displacement and an underestimation by approximately 7% of the maximum computed leaflet velocity. CONCLUSION: The weakly coupled approach adopted here limited computational costs, thus allowing the simulation of a fully 3-D realistic mechanical valve within 154 CPU hours at minimal computational costs. No significant drawbacks were raised in comparison with the fully coupled approach. The opening process delay was similar to that reported previously, and cannot be ascribed to the weakly coupled approach adopted here.

Biomechanical Phenomena↗
PubMed2003

Experimental validation of Monte Carlo modeling of fluorescence in tissues in the UV-visible spectrum.

The goal of the work is to experimentally verify Monte Carlo modeling of fluorescence and diffuse reflectance measurements in turbid, tissue phantom models. In particular, two series of simulations and experiments, in which one optical parameter (absorption or scattering coefficient) is varied while the other is fixed, are carried out to assess the effect of the absorption coefficient (mu(a)) and scattering coefficient (mu(s)) on the fluorescence and diffuse reflectance measured from a turbid medium. Moreover, simulations and experiments are carried out for several fiber optic probe geometries that are designed to sample small tissue volumes. Additionally, a group of conversion expressions are derived to convert the optical properties and fluorescence quantum yield measured from tissue phantoms for use in Monte Carlo simulations. The conversions account for the differences between the definitions of the absorption coefficient and fluorescence quantum yield of fluorophores in a tissue phantom model and those in a Monte Carlo simulation. The results indicate that there is good agreement between the simulated and experimentally measured results in most cases. This dataset can serve as a systematic validation of Monte Carlo modeling of fluorescent light propagation in tissues. The simulations are carried out for a wide range of absorption and scattering coefficients as well as ratios of scattering coefficient to absorption coefficient, and thus would be applicable to tissue optical properties over a wide wavelength range (UV-visible/near infrared). The fiber optic probe geometries that are modeled in this study include those commonly used for measuring fluorescence from tissues in practice.

Absorption↗
PubMed2001

Quod erat demonstrandum? The mystery of experimental validation of apparently erroneous computational analyses of protein sequences.

BACKGROUND: Computational predictions are critical for directing the experimental study of protein functions. Therefore it is paradoxical when an apparently erroneous computational prediction seems to be supported by experiment. RESULTS: We analyzed six cases where application of novel or conventional computational methods for protein sequence and structure analysis led to non-trivial predictions that were subsequently supported by direct experiments. We show that, on all six occasions, the original prediction was unjustified, and in at least three cases, an alternative, well-supported computational prediction, incompatible with the original one, could be derived. The most unusual cases involved the identification of an archaeal cysteinyl-tRNA synthetase, a dihydropteroate synthase and a thymidylate synthase, for which experimental verifications of apparently erroneous computational predictions were reported. Using sequence-profile analysis, multiple alignment and secondary-structure prediction, we have identified the unique archaeal 'cysteinyl-tRNA synthetase' as a homolog of extracellular polygalactosaminidases, and the 'dihydropteroate synthase' as a member of the beta-lactamase-like superfamily of metal-dependent hydrolases. CONCLUSIONS: In each of the analyzed cases, the original computational predictions could be refuted and, in some instances, alternative strongly supported predictions were obtained. The nature of the experimental evidence that appears to support these predictions remains an open question. Some of these experiments might signify discovery of extremely unusual forms of the respective enzymes, whereas the results of others could be due to artifacts.

Acetyltransferases↗
PubMedDate not supplied

[Experimental validation of the efficacy of intraocular phonoelectrophoresis in eye diseases].

Basing on clinical data (12 patients) and experimental results (42 rabbits), the authors defined the pharmacokinetic characteristics of drugs administered by endo-ocular phonoelectrophoresis technique developed by them. Formation of the drugs' depot in the parabulbar space was demonstrated. Concentrations of the administered drugs in various segments of the eyeball were assessed. The values obtained during parabulbar injection of drugs were used as reference ones.

Adult↗
PubMed2006

Electrode boundary conditions and experimental validation for BEM-based EIT forward and inverse solutions.

In this paper, we present theoretical developments and experimental results for the problem of estimating the conductivity map inside a volume using electrical impedance tomography (EIT) when the boundary locations of any internal inhomogeneities are known. We describe boundary element method (BEM) implementations of advanced electrode models for the forward problem of EIT. We then use them in the inverse problem with known internal boundaries and derive the associated Jacobians. We report on the results of two EIT phantom studies, one using a homogeneous cubical tank, and one using a cylindrical tank with agar conductivity inhomogeneities. We test both the accuracy of our BEM forward model, including the electrode models, as well as our inverse solution, against the measured data. Results show good agreement between measured values and both forward-computed tank voltages and inverse-computed conductivities; for instance, in a phantom experiment, we reconstructed the conductivities of three agar objects inside a cylindrical tank with an error less than 2% of their true value.

Algorithms↗
PubMedDate not supplied

[An experimental validation of pharmacological agents to arrest the vestibulo-autonomic syndrome (motion sickness)].

The results of development and experimental evaluation of the efficiency of pharmacological means of cupping the vestibulo-vegetative syndrome in man are presented. A model and procedure of evaluation of pharmacological cupping of the Vestibulo-vegetative syndrome are developed. The intramuscular injection of the mixture containing ephedrine, promethazine hydrochloride and strychnine (25, 50, and 1 mg, respectively) appeared most effective.

Coriolis Force↗