Characterization of the Cytochrome P450 epoxyeicosanoid pathway in non-alcoholic steatohepatitis

Non-alcoholic steatohepatitis (NASH) is an emerging public health problem without effective therapies. Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid into bioactive epoxyeicosatrienoic acids (EETs), which have potent anti-inflammatory and protective effects. However, the functional relevance of the CYP epoxyeicosanoid metabolism pathway in the pathogenesis of NASH remains poorly understood. Our studies demonstrate that both mice with methionine-choline deficient (MCD) diet-induced NASH and humans with biopsy-confirmed NASH exhibited significantly higher free EET concentrations compared to healthy controls. Targeted disruption of Ephx2 (the gene encoding for soluble epoxide hydrolase) in mice further increased EET levels and significantly attenuated MCD diet-induced hepatic steatosis, inflammation and injury, as well as high fat diet-induced adipose tissue inflammation, systemic glucose intolerance and hepatic steatosis. Collectively, these findings suggest that dysregulation of the CYP epoxyeicosanoid pathway is a key pathological consequence of NASH in vivo, and promoting the anti-inflammatory and protective effects of EETs warrants further investigation as a novel therapeutic strategy for NASH

Datafiles: Local Shearing Force Measurement during Frictional Sliding Using Fluorogenic Mechanophores

The raw data and the Matlab code for the publication : Chao-Chun Hsu, Feng-Chun Hsia, Bart Weber, Matthijn B. de Rooij, Daniel Bonn, and Albert M. Brouwer,  Local Shearing Force Measurement during Frictional Sliding Using Fluorogenic Mechanophores, The Journal of Physical Chemistry Letters 2022 13 (38), 8840-8844 10.1021/acs.jpclett.2c02010 Citation: DOI: 10.1021/acs.jpclett.2c02010 Please find more details in the Readme file at each archive file. </p

Datafiles: Local Shearing Force Measurement during Frictional Sliding Using Fluorogenic Mechanophores

The raw data and the Matlab code for the publication : Chao-Chun Hsu, Feng-Chun Hsia, Bart Weber, Matthijn B. de Rooij, Daniel Bonn, and Albert M. Brouwer,  Local Shearing Force Measurement during Frictional Sliding Using Fluorogenic Mechanophores, The Journal of Physical Chemistry Letters 2022 13 (38), 8840-8844 10.1021/acs.jpclett.2c02010 Citation: DOI: 10.1021/acs.jpclett.2c02010 Please find more details in the Readme file at each archive file. </p

Optimization of folic acid, vitamin B-12, and vitamin B-6 supplements in pediatric patients with sickle cell disease

Using homocysteine as a functional marker, we determined optimal folic acid, vitamin B-12, and vitamin B-6 dosages in 21 pediatric sickle cell disease (SCD) patients (11 HbSS, 10 HbSC; 7-16 years). Daily supplements of folic acid (400, 700, or 1,000 mug), vitamin B-12 (1, 3, or 5 U.S. 1989 RDA), and vitamin B-6 (1 or 3 U.S. 1989 RDA) were gradually increased in an 82-week dose-escalation study. Blood was taken at 9 occasions for measurements of erythrocyte (RBC) and serum folate, plasma vitamin B-12, whole-blood vitamin B-6, and plasma homocysteine. Augmentation of folic acid from 700 to 1,000 mug and vitamin B-12 from 3 to 5 RDA did not further decrease homocysteine. Percentages of patients exhibiting significant individual homocysteine decreases amounted to 43% (folic acid from 0 to 400 mug, vitamins B-12 and B-6 from 0 to 1 RDA), 14% (folic acid from 400 to 700 mug), 24% (vitamin B-12 from 1 to 3 RDA), and 18% (vitamin B-6 from 1 to 3 RDA). The lowest plasma homocysteine at 82 weeks was 5.9 +/- 2.2 mumol/L. Patients with HbSS had higher RBC folate than HbSC. The entire group exhibited an inverse relation between RBC folate and hemoglobin. We conclude that RBC folate is less valuable for folate status assessment in SCD patients. Optimal dosages are as follows: 700 mug folic acid (3.5-7 U.S. 1989 RDA), 3 U.S. 1989 RDA vitamin B-12 (4.2-6.0 mug), and 3 U.S. 1989 RDA vitamin B-6 (4.2-6.0 mg). A practical daily combination is 1 mg folic acid (4.3-8.5 U.S. 1998 RDA when taken with meals), 6 mug vitamin B-12 (2.5-5 U.S. 1998 RDA), and 6 mg vitamin B-6 (4.6-10 U.S. 1998 RDA). This combination may by simple and relatively inexpensive means reduce these patients' inherently high risk of endothelial damage

Can Teacher Education Make a Difference?

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Validation of the ACR-EULAR criteria for primary Sjogren's syndrome in a Dutch prospective diagnostic cohort

Objectives. To validate the ACR-EULAR classification criteria for primary SS (pSS), and compare them to the American-European Consensus Group (AECG) and ACR criteria in a Dutch prospective diagnostic cohort. Methods. Consecutive patients (n = 129) referred for suspicion of pSS underwent a multidisciplinary evaluation, including a labial and/or parotid gland biopsy. Patients with an incomplete work-up (n= 8) or associated systemic auto-immune disease (n= 7) were excluded. The ACR-EULAR classification was compared with expert classification, AECG and ACR classification. Additionally, the accuracy of individual ACR-EULAR items in discriminating pSS from non-pSS was evaluated. The validity of criteria sets was described separately using parotid or labial gland biopsy results for classification. Results. Of the 114 evaluated patients, the expert panel classified 34 (30%) as pSS and 80 (70%) as non-pSS. Using labial gland biopsy results, ACR-EULAR classification showed 87% absolute agreement (kappa = 0.73) with expert classification, with a sensitivity of 97% and specificity of 83%. Using the parotid gland biopsy results, the ACR-EULAR criteria performed excellently as well. Focus score, anti-SSA titre and ocular staining score showed good to excellent accuracy, whereas unstimulated whole saliva and Schirmer's test had poor accuracy. The ACR-EULAR and AECG criteria had equal validity. Compared with ACR classification, ACR-EULAR classification showed higher sensitivity but lower specificity. Conclusion. The ACR-EULAR criteria showed good agreement with expert classification, but some patients may be misclassified as pSS. Unstimulated whole saliva and Schirmer's test showed poor discriminative value. The ACR-EULAR criteria performed equally to the AECG criteria, and had higher sensitivity but lower specificity than the ACR criteria