Genetic polymorphisms in plasminogen activator inhibitor-1 predict susceptibility to steroid-induced osteonecrosis of the femoral head in Chinese population

BACKGROUND: Steroid usage has been considered as a leading cause of non-traumatic osteonecrosis of the femoral head (ONFH), which is involved in hypo-fibrinolysis and blood supply interruption. Genetic polymorphisms in plasminogen activator inhibitor-1 (PAI-1) have been demonstrated to be associated with ONFH risk in several populations. However, this relationship has not been established in Chinese population. The aim of this study was to investigate the association of PAI-1 gene polymorphisms with steroid-induced ONFH in a large cohort of Chinese population. METHODS: A case–control study was conducted, which included 94 and 106 unrelated patients after steroid administration recruited from 14 provinces in China, respectively. Two SNPs (rs11178 and rs2227631) within PAI-1 were genotyped using Sequenom MassARRAY system. RESULTS: rs2227631 SNP was significantly associated with steroid-induced ONFH group in codominant (P = 0.04) and recessive (P = 0.02) models. However, there were no differences found in genotype frequencies of rs11178 SNP between controls and patients with steroid-induced ONFH (all P > 0.05). CONCLUSIONS: Our data offer the convincing evidence for the first time that rs2227631 SNP of PAI-1 may be associated with the risk of steroid-induced ONFH, suggesting that the genetic variations of this gene may play an important role in the disease development. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1569909986109783

Exploring the potentials of Sesuvium portulacastrum L. for edibility and bioremediation of saline soils

Sesuvium portulacastrum L. is a flowering succulent halophyte in the ice plant family Aizoaceae. There are various ecotypes distributed in sandy coastlines and salty marshlands in tropical and subtropical regions with the common name of sea purslane. These plants are tolerant to salt, drought, and flooding stresses and have been used for the stabilization of sand dunes and the restoration of coastal areas. With the increased salinization of agricultural soils and the widespread pollution of toxic metals in the environment, as well as excessive nutrients in waterbodies, S. portulacastrum has been explored for the desalination of saline soils and the phytoremediation of metals from contaminated soils and nitrogen and phosphorus from eutrophic water. In addition, sea purslane has nutraceutical and pharmaceutical value. Tissue analysis indicates that many ecotypes are rich in carbohydrates, proteins, vitamins, and mineral nutrients. Native Americans in Florida eat it raw, pickled, or cooked. In the Philippines, it is known as atchara after being pickled. S. portulacastrum contains high levels of ecdysteroids, which possess antidiabetic, anticancer, and anti-inflammatory activities in mammals. In this review article, we present the botanical information, the physiological and molecular mechanisms underlying the tolerance of sea purslane to different stresses, its nutritional and pharmaceutical value, and the methods for its propagation and production in saline soils and waterbodies. Its adaptability to a wide range of stressful environments and its role in the production of valuable bioactive compounds suggest that S. portulacastrum can be produced in saline soils as a leafy vegetable and is a valuable genetic resource that can be used for the bioremediation of soil salinity and eutrophic water

Implications of C1q/TNF-related protein superfamily in patients with coronary artery disease.

The C1q complement/TNF-related protein superfamily (CTRPs) displays differential effects on the regulation of metabolic homeostasis, governing cardiovascular function. However, whether and how they may serve as predictor/pro-diagnosis factors for assessing the risks of coronary artery disease (CAD) remains controversial. Therefore, we performed a clinical study to elaborate on the implication of CTRPs (CTRP1, CTRP5, CTRP7, and CTRP15) in CAD. CTRP1 were significantly increased, whereas CTRP7 and CTRP15 levels were decreased in CAD patients compared to the non-CAD group. Significant differences in CTRP1 levels were discovered between the single- and triple-vascular-vessel lesion groups. ROC analysis revealed that CTRP7 and CTRP15 may serve as CAD markers, while CTRP1 may serve as a marker for the single-vessel lesion of CAD. CTRP1 and CTRP5 can serve as markers for the triple-vessel lesion. CTRP1 may serve as an independent risk predictor for triple-vessel lesion, whereas CTRP15 alteration may serve for a single-vessel lesion of CAD. CTRP1 may serve as a novel superior biomarker for diagnosis of severity of vessel-lesion of CAD patients. CTRP7, CTRP15 may serve as more suitable biomarker for the diagnosis of CAD patients, whereas CTRP5 may serve as an independent predictor for CAD. These findings suggest CTRPs may be the superior predictive factors for the vascular lesion of CAD and represent novel therapeutic targets against CAD

Evaluating cardiac function with chest computed tomography in acute ischemic stroke: feasibility and correlation with short-term outcome

BackgroundThe outcomes of patients with acute ischemic stroke (AIS) are related to cardiac function. Cardiac insufficiency can manifest as hydrostatic changes in the lungs. Computed tomography (CT) of the chest is commonly used for screening pulmonary abnormalities and provides an opportunity to assess cardiac function.PurposeTo evaluate the correlation between hydrostatic lung manifestations on chest CT and cardiac function with its potential to predict the short-term outcome of AIS patients.MethodsWe retrospectively analyzed AIS patients who had undergone chest CT at admission and echocardiogram within 48 h. Morphological and quantitative hydrostatic changes and left ventricular dimensions were assessed using chest CT. Improvement in the National Institutes of Health Stroke Scale (NIHSS) score on the seventh day determined short-term outcomes. Multivariate analysis examined the correspondence between hydrostatic lung manifestations, left ventricular dimension, and left ventricle ejection fraction (LVEF) on echocardiography, and the correlation between hydrostatic changes and short-term outcomes.ResultsWe included 204 patients from January to December 2021. With the progression of hydrostatic changes on chest CT, the LVEF on echocardiography gradually decreased (p < 0.05). Of the 204, 53 patients (26%) with varying degrees of hypostatic lung manifestations had less improvement in the NIHSS score (p < 0.05). The density ratio of the anterior/posterior lung on CT showed a significant negative correlation with improvement in the NIHSS score (r = −5.518, p < 0.05). Additionally, patients with a baseline NIHSS ≥4 with left ventricular enlargement had significantly lower LVEF than that of patients with normal NIHSS scores.ConclusionHydrostatic lung changes on chest CT can be used as an indicator of cardiac function and as a preliminary reference for short-term outcome in AIS patients

CIS UDEL Working Notes on ImageCLEF 2015: Compound figure detection task

Abstract. Figures that are included in biomedical publications play an important role in understanding essential aspects of the paper. Much work over the past few years has focused on figure analysis and classification in biomedical documents. As many of the figures appearing in biomedical documents comprise multiple panels (subfigures), the first step in the analysis requires identification of compound figures and their segmentation into subfigures. There is a wide variety ways to detect compound figures. In this paper, we utilize only visual information to identify compound vs non-compound figures. We have tested the proposed approach on the ImageCLEF 2015 benchmark of 10, 434 images; our approach has achieved an accuracy of 82.82%, thus demonstrating the best performance when compared to other systems that use only visual information for addressing the compound figure detection task

Preclinical characterization of tunlametinib, a novel, potent, and selective MEK inhibitor

Background: Aberrant activation of RAS-RAF-MEK-ERK signaling pathway has been implicated in more than one-third of all malignancies. MEK inhibitors are promising therapeutic approaches to target this signaling pathway. Though four MEK inhibitors have been approved by FDA, these compounds possess either limited efficacy or unfavorable PK profiles with toxicity issues, hindering their broadly application in clinic. Our efforts were focused on the design and development of a novel MEK inhibitor, which subsequently led to the discovery of tunlametinib.Methods: This study verified the superiority of tunlametinib over the current MEK inhibitors in preclinical studies. The protein kinase selectivity activity of tunlametinib was evaluated against 77 kinases. Anti-proliferation activity was analyzed using the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) or (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS) assay. ERK and phospho-ERK levels were evaluated by Western blot analysis. Flow cytometry analysis was employed to investigate cell cycle and arrest. Cell-derived xenograft (CDX) and Patient-derived xenograft (PDX) models were used to evaluate the tumor growth inhibition. The efficacy of tunlametinib as monotherapy treatment was evaluated in KRAS/BRAF mutant or wild type xenograft model. Furthermore, the combination studies of tunlametinib with BRAF/KRASG12C/SHP2 inhibitors or chemotherapeutic agent were conducted by using the cell proliferation assay in vitro and xenograft models in vivo.Results:In vitro, tunlametinib demonstrated high selectivity with approximately 19-fold greater potency against MEK kinase than MEK162, and nearly 10–100-fold greater potency against RAS/RAF mutant cell lines than AZD6244. In vivo, tunlametinib resulted in dramatic tumor suppression and profound inhibition of ERK phosphorylation in tumor tissue. Mechanistic study revealed that tunlametinib induced cell cycle arrest at G0/G1 phase and apoptosis of cells in a dose-proportional manner. In addition, tunlametinib demonstrated a favorable pharmacokinetic profile with dose-proportionality and good oral bioavailability, with minimal drug exposure accumulation. Furthermore, tunlametinib combined with BRAF/KRASG12C/SHP2 inhibitors or docetaxel showed synergistically enhanced response and marked tumor inhibition.Conclusion: Tunlametinib exhibited a promising approach for treating RAS/RAF mutant cancers alone or as combination therapies, supporting the evaluation in clinical trials. Currently, the first-in-human phase 1 study and pivotal clinical trial of tunlametinib as monotherapy have been completed and pivotal trials as combination therapy are ongoing