Follistatin-like 1 protects endothelial function in the spontaneously hypertensive rat by inhibition of endoplasmic reticulum stress through AMPK-dependent mechanism.

OBJECTIVE: Endothelial dysfunction is a critical initiating factor in the development of hypertension and related complications. Follistatin-like 1 (FSTL1) can promote endothelial cell function and stimulates revascularization in response to ischemic insult. However, it is unclear whether FSTL1 has an effect on ameliorating endothelial dysfunction in spontaneously hypertensive rats (SHRs). METHODS: Wistar Kyoto (WKY) and SHRs were treated with a tail vein injection of vehicle (1 mL/day) or recombinant FSTL1 (100 µg/kg body weight/day) for 4 weeks. Blood pressure was measured by tail-cuff plethysmograph, and vascular reactivity in mesenteric arteries was measured using wire myography. RESULTS: We found that treatment with FSTL1 reversed impaired endothelium-dependent relaxation (EDR) in mesenteric arteries and lowered blood pressure of SHRs. Decreased AMP-activated protein kinase (AMPK) phosphorylation, elevated endoplasmic reticulum (ER) stress markers, increased reactive oxygen species (ROS), and reduction of nitric oxide (NO) production in mesenteric arteries of SHRs were also reversed by FSTL1 treatment. Ex vivo treatment with FSTL1 improved the impaired EDR in mesenteric arteries from SHRs and reversed tunicamycin (ER stress inducer)-induced ER stress and the impairment of EDR in mesenteric arteries from WKY rats. The effects of FSTL1 were abolished by cotreatment of compound C (AMPK inhibitor). CONCLUSIONS: These results suggest that FSTL1 prevents endothelial dysfunction in mesenteric arteries of SHRs through inhibiting ER stress and ROS and increasing NO production via activation of AMPK signaling.

Distal radial access for neuroangiography and neurointerventions: systematic review and meta-analysis.

BACKGROUND: Many studies have shown that coronary angiography (CAG) and percutaneous coronary intervention (PCI) via distal radial access (DRA) are safe and effective. Safety and efficacy of neuroangiography and neurointerventions via DRA are unknown. PURPOSE: Search the literatures on neuroangiography and neurointerventions via DRA and conduct a systematic review and meta-analysis. METHODS: PubMed, Embase and Cochrane were searched from inception to November 10, 2022. After literature screening, data extraction and assessment of literature quality, random effects model was used for meta-analysis. RESULTS: A total of 236 literatures were retrieved, and 17 literatures including 1163 patients were finally included for meta-analysis.The pooled access success rate was 0.96 (95% confidence interval, 0.94-0.98), and the heterogeneity was obvious (I2 = 55.5%). The pooled access-related complications incidence rate was 0.03 (95% confidence interval, 0.02-0.05), and the heterogeneity was not obvious (I2 = 15.8%). CONCLUSION: Neuroangiography and neurointerventions via DRA may be safe and effective. DRA is an alternative access for neuroangiography and neurointerventions.

Farnesoid X receptor is an important target for the treatment of disorders of bile acid and fatty acid metabolism in mice with nonalcoholic fatty liver disease combined with cholestasis.

BACKGROUND AND AIM: The prevalence of nonalcoholic fatty liver disease (NAFLD) has been rising globally. NAFLD patients combined with cholestasis have more obvious liver fibrosis, impaired bile acid (BA), and fatty acid (FA) metabolism and severer liver injury; however, its therapeutic options are limited, and the underlying metabolic mechanisms are understood. Here, we aimed to investigate the effects of farnesoid X receptor (FXR) on BA and FA metabolism in NAFLD combined with cholestasis and related signaling pathways. METHODS: A mouse model of NAFLD combined with cholestasis was established by joint intervention with high-fat diet (HFD) and alpha-naphthylisothiocyanate. The effects of FXR on BA and FA metabolism were evaluated by serum biochemical analysis. Liver damage was identified by histopathology. The expression of nuclear hormone receptor, membrane receptor, FA transmembrane transporter, and BA transporter protein in mice were measured by western blot. RESULTS: NAFLD mice combined with cholestasis developed more severe cholestasis and dysregulated BA and FA metabolism. Meanwhile, the expression of FXR protein was decreased in NAFLD mice combined with cholestasis compared to the controls. Fxr-/- mice showed liver injury. HFD aggravated the liver injury with decreased BSEP expression, increased expression of NTCP, LXRα, SREBP-1c, FAS, ACC1, and CD36, and significantly increased BA and FA accumulation. CONCLUSION: All the results suggested that FXR plays a key role in both FA and BA metabolism in NAFLD combined with cholestasis and thus may be a potential target for the treatment of disorders of BA and FA metabolism in NAFLD combined with cholestasis.

Quantitative analysis of phenanthrene in soil by fluorescence spectroscopy coupled with the CARS-PLS model.

Polycyclic aromatic hydrocarbons (PAHs) are typical organic pollutants in soil and are teratogenic and carcinogenic. Therefore, rapid and accurate analysis of PAHs in soil can provide a theoretical basis and data support for soil contamination risk assessment. In this work, a fluorescence spectroscopy technique combined with partial least squares (PLS) was proposed for rapid quantitative analysis of phenanthrene (PHE) in soil. At first, the fluorescence spectra of 29 soil samples with different concentrations (0.3-10 mg g-1) of PHE were collected by RF-5301 PC fluorescence spectrophotometer. Secondly, the effects of different spectral preprocessing methods were investigated on the prediction performance of the PLS calibration model. And then, the influence of competitive adaptive reweighted sampling (CARS) wavelength points on the prediction performance of PLS calibration model was discussed. Finally, according to the selected wavelength points, a quantitative analytical model for PHE content in soil was constructed using the PLS calibration method. To further explore the predictive performance of the CARS-PLS calibration model, the predictive results were compared with those of the RAW spectrum-partial least squares calibration model (RAW-PLS) and the wavelet transform-standard normal variation (WT-SNV) calibration model. The CARS-PLS calibration model showed the optimal predictive performance and its coefficient of determination of cross-validation (R cv 2) and root mean square error of 10-fold cross-validation (RMSEcv) were 0.9957 and 18.98%, respectively. The coefficient of determination of prediction set (R p 2) and root mean square error of prediction set (RMSEp) were 0.9963 and 16.13%, respectively. Hence, the CARS algorithm based on fluorescence spectrum coupled with PLS can give a rapid and accurate quantitative analysis of the PHE content in soil.

Novel Random Forest Ensemble Modeling Strategy Combined with Quantitative Structure-Property Relationship for Density Prediction of Energetic Materials.

With the further development of the concept of green chemistry, the new generation of energetic materials tends to exhibit detonation properties such as higher insensitivity, higher density, and higher energy. Therefore, the precise molecular design and green and efficient synthesis of energetic materials will be one of the serious challenges. For the purpose of accurate prediction of detonation performance of energetic materials, an ensemble modeling strategy based on the combination of Monte Carlo (MC) and variable importance measurement (VIM) improved random forest (RF) and quantitative structure-property relationship (QSPR) is proposed, which was successfully used for density prediction of energetic materials. First, the structure of 162 energetic compounds was optimized by Gaussian software, and the molecular descriptor data were calculated by CODESSA software based on the optimized molecular structure. Then, the MCVIMRF_Med ensemble model was constructed on the basis of the above molecular descriptor data and the corresponding energetic compound density index. The joint X-Y distance algorithm (SPXY) is used to partition the data set. And then, MC is used to further divide the calibration set data into multiple subsets for the construction of the ensemble model. The subset size and the number of iterations of the MCVIMRF_Med ensemble model were optimized through MC cross validation. The final output strategy of the ensemble model is optimized based on the optimized parameters, and an output optimization method based on median screening is proposed and successfully applied for the prediction performance optimization of the MCVIMRF_Med ensemble model. To further investigate the performance of the MCVIMRF_Med ensemble model, the performance of it was compared with partial least squares, RF, VIMRF, and MCVIMRF calibration models. It shows that the MCVIMRF_Med ensemble model can achieve a better prediction result for the density of energetic materials, with R 2 CV of 0.9596, RMSECV of 0.0437 g/cm3, R 2 P of 0.9768, RMSEP of 0.0578 g/cm3, and relative analysis deviation of prediction set of 3.951. Therefore, the MCVIMRF_Med ensemble modeling strategy combined with QSPR is an effective approach for the density prediction of energetic materials. This work is expected to provide new research ideas and technical support for accurate prediction of detonation performance of energetic materials.

On-line Raman spectroscopy combined with multivariate curve resolution-alternating least squares (MCR-ALS) to investigate the synthesis mechanism of 3,5-diamino-1,2,4-triazole (DAT).

The precise and accurate synthesis mechanism of typical energetic materials (EMs) intermediate is extremely important for the optimization of synthesis technology of EMs. In this research, on-line Raman spectroscopy technique combined with multivariate curve resolution-alternating least squares(MCR-ALS) method was proposed and used to investigate the synthesis mechanism of EMs intermediate (3,5-diamino-1,2,4-triazole, DAT). Initially, on-line Raman spectroscopy was applied to collect the Raman spectral data of DAT synthesis process. Secondly, principal component analysis (PCA), coupled with singular value decomposition (SVD) were used to determine the number of component of the reaction system and the components was 5. Thirdly, MCR-ALS was used to extract the pure Raman spectra and concentration curves of each substance of DAT synthesis process. During the MCR-ALS operation, evolving factor analysis (EFA) was choose to acquire the initial concentration estimation for MCR-ALS. Several constraints were selected to apply to ALS optimization including non-negative, closure, equality and correlation constraint. And the correlation coefficient between the Raman spectra and the actual Raman spectra of the hydrazine hydrochloride, dicyandiamide and DAT was calculated, their correlation coefficient R2 were 0.9522, 0.9446, 0.9908 respectively which showed a good data fit of MCR-ALS method. Finally, according to the results of MCR-ALS analysis, the structure of the synthetic intermediates was successfully deduced and the mechanism of DAT synthesis was proposed. Hence, a precise and comprehensive method for analyzing the DAT synthesis reaction mechanism is proposed, which is helpful to provide a new idea for the analysis of the synthesis reaction mechanism of energetic materials.

Quantitative analysis of polycyclic aromatic hydrocarbons (PAHs) in water by surface-enhanced Raman spectroscopy (SERS) combined with Random Forest.

Polycyclic aromatic hydrocarbons (PAHs) have strong carcinogenicity, teratogenicity, mutagenicity and other adverse effects on human beings. They are one of the most dangerous pollutants, which have attracted great attention in the past decades. In this work, aiming at the actual problems that water environment is polluted and human health is threatened by PAHs, surface enhanced Raman spectroscopy (SERS) combined with Random Forest (RF) calibration models were used to quantitative analysis of phenanthrene and fluoranthene in water. Firstly, the SERS data was collected after samples mixed with Ag NPs, after 31 PAHs samples were prepared. Secondly, it was discussed how spectral preprocessing integration strategies affect on the prediction performance of the RF calibration models. And then, the effect of mutual information (MI) variable selection method on the performance of RF calibration models was explored. Finally, the RF calibration models were established for phenanthrene and fluoranthene. For the prediction set, a lowest mean relative error (MRE) and a largest determination coefficient (R2) were obtained. For quantitative analysis of phenanthrene, the final prediction performance results show that R2p is 0.9780, and MREp is 0.0369 based on the D1st-WT-RF calibration model. For fluoranthene, WT-D1st-MI-RF is a better calibration model, and corresponding to R2p and MREp are 0.9770 and 0.0694, respectively. Hence, a rapid and accurate quantitative method of PAHs is established for the real-time detection of water environmental pollution, which is intended to provide new ideas and methods for the quantitative analysis of PAHs in water.

Novel neutralizing chicken IgY antibodies targeting 17 potent conserved peptides identified by SARS-CoV-2 proteome microarray, and future prospects.

Introduction: An approach toward novel neutralizing IgY polyclonal antibodies (N-IgY-pAb) against SARS-CoV-2 S-ECD was developed. Material and methods: The novel N-IgY-pAb and its intranasal spray response against the wild type ("'WH-Human 1") SARS-CoV-2 virus, variants of Delta or Omicron were up to 98%. Unique virus peptides binding to N-IgY-pAb were screened by a SARS-CoV-2 proteome microarray. Results: Seventeen mutation-free peptides with a Z-score > 3.0 were identified as potent targets from a total of 966 peptides. The new findings show that one is in the RBM domain (461LKPFERDISTEIYQA475 ), two are in the NTD domain (21RTQLPPAYTNSFTRG35, 291CALDPLSETKCTLKS305) four are in the C1/2-terminal (561PFQQFGRDIADTTDA575,571DTTDAVRDPQTLEIL585,581TLEILDITPCSFGGV595, 661ECDIPIGAGICASYQ675 ), three are in the S1/S2 border (741YICGDSTECSNLLLQ755, 811KPSKRSFIEDLLFNK825, 821LLFNKVTLADAGFIK835) one target is in HR2 (1161SPDVDLGDISGINAS1175) and one is in HR2-TM (1201QELGKYEQYIKWPWY1215). Moreover, five potential peptides were in the NSP domain: nsp3-55 (1361SNEKQEILGTVSWNL1375), nsp14-50 (614HHANEYRLYLDAYNM642, ORF10-3 (21MNSRNYIAQVDVVNFNLT38, ORF7a-1(1MKIILFLALITLATC15) and ORF7a-12 (1116TLCFTLKRKTE121). Discussion and conclusion: We concluded that the N-IgY-pAb could effectively neutralize the SARS-CoV-2. The new findings of seventeen potent conserved peptides are extremely important for developing new vaccines and "cocktails" of neutralizing Abs for efficient treatments for patients infected with SARS-CoV-2.

Pollution risk estimation of the Cu element in atmospheric sedimentation samples by laser induced breakdown spectroscopy (LIBS) combined with random forest (RF).

Laser-induced breakdown spectroscopy (LIBS) combined with the random forest (RF) algorithm was proposed to predict three pollution indexes (geo-accumulation index, enrichment factor, and potential ecological risk index) of the Cu element in atmospheric sedimentation samples to evaluate the pollution risk. To begin with, the LIBS spectra of 15 atmospheric sedimentation samples from different locations were collected and the copper element was identified using the National Institute of Standards and Technology (NIST) database. Then, the influence of different spectral pretreatment methods (MSC, WT and D1st) on the predictive performance of the RF was discussed according to the calibration set with the determination coefficient (Rc2) and mean relative error (MREC) as evaluation indexes. Next, in order to obtain a better RF calibration model, a variable importance (VI) measurement was applied to select input variables from LIBS spectral data based on the optimal spectral pretreatment method, and the optimal variable importance threshold was selected as the input variable to establish the RF calibration model. Finally, the predictive performance of the optimal RF calibration model was verified using the prediction set with the determination coefficient (Rp2) and the mean relative error (MREP). The results show that Rp2 of the geo-accumulation index, enrichment factor and potential ecological risk index is up to 0.9971, 0.9919 and 0.9290, respectively, and MREP of the three indexes is 0.0234, 0.1173 and 0.0810, respectively; the average relative standard deviation (RSD) of the prediction set for the three indexes is 2.16%, 5.78% and 0.71%, respectively. Furthermore, it can be inferred that Cu was at levels corresponding to serious pollution primarily because of anthropogenic activities based on the predictive Igeo, Er and RI values. Therefore, LIBS combined with the RF algorithm is a promising means which can achieve fast and simple estimation of the pollution risk degree of Cu in atmospheric sedimentation samples without complicated sample preparation to provide a basis for pollution prevention and control measures.

Quantitative analysis of polycyclic aromatic hydrocarbons in soil by infrared spectroscopy combined with hybrid variable selection strategy and partial least squares.

Infrared spectroscopy (IR) combined with multivariate calibration technology can be used as a potential method to quantitative analysis of polycyclic aromatic hydrocarbons (PAHs) in soil, which provides a rapid data support for soil risk assessment. However, IR spectrum contains lots of useless information, its predictive performance is poor. Variable selection is an effective strategy to eliminate irrelevant wavelengths and enhance predictive performance. In this study, IR combined with partial least squares (PLS) was proposed to quantify anthracene and fluoranthene in soil. In order to improve the predictive performance of the PLS calibration model, the synergy interval PLS (siPLS) method was first used for "rough selection" to select feature bands; on this basis, "fine selection" was performed to extract the feature variables. In "fine selection", three different feature variables selection methods, such as successive projection algorithm (SPA), genetic algorithm (GA), and particle swarm optimization (PSO), were compared for their performance in extracting effective variables. The results show that the siPLS-GA calibration model receive a lowest root mean square error (RMSE) and a largest determination coefficient (R2). Results of external validation demonstrate an excellent predictive performance of siPLS-GA calibration model, with the R2 = 0.9830, RMSE = 0.5897 mg/g and R2 = 0.9849, RMSE = 0.4739 mg/g for anthracene and fluoranthene, respectively. In summary, siPLS combined with GA can accurately extract the effective information of the target substance and improve the predictive performance of the PLS calibration model based on IR spectroscopy.

Hybrid variable selection strategy coupled with random forest (RF) for quantitative analysis of methanol in methanol-gasoline via Raman spectroscopy.

With the trend of portable and miniaturization, Raman spectrometer requires more advanced analytical methods providing more rapid and accurate analysis performance for in-situ analysis. In this work, a hybrid variable selection method based on V-WSP and variable importance measurement (VIM) coupled with random forest (RF) was used to improve the quantitative analysis performance of portable laser Raman instruments for quantitative analysis of methanol content in methanol gasoline. First, five preprocessing methods were applied to reduce the infection information in the raw spectra, respectively. Based on the spectra data processed by multivariate scattering correction (MSC), V-WSP was employed to filter the infection or redundant information in Raman spectroscopy, and 579 variables were obtained when the correlation threshold is 0.9600. Then, the variables were further eliminated by VIM. Finally, 43 variables were obtained by the V-WSP-VIM method. In data processing, out of bag (OOB) error estimation and 10-flod cross validation (CV) were applied to optimize the parameters of preprocessing methods, V-WSP, VIM and RF model. The results fully demonstrated that compared with the RF model based on raw spectra, the RF model based on V-WSP-VIM method can achieve a better prediction performance for the quantitative analysis of methanol content in methanol-gasoline, with the coefficients of determination of cross-validation (R2CV) improving from 0.9100 to 0.9662, the root mean square error of cross-validation (RMSECV) reducing from 0.0572 to 0.0365%, the coefficients of determination of prediction set (R2P) improving from 0.9214 to 0.9407, the root mean square error of prediction set (RMSEP) reducing from 0.0420 to 0.0382%, the variables reducing from 1044 to 43 and the modeling time reducing from 72.94 to 6.41 s. The results indicates that V-WSP-VIM coupled with RF is an effective method to improve the performance of portable laser Raman spectrometer for quantitative analysis of methanol content in methanol gasoline.

Histone deacetylase 11 inhibits interleukin 10 in B cells of subjects with allergic rhinitis.

BACKGROUND: The interleukin (IL)-10 expression in B cells plays an important role in immune tolerance. The regulation of IL-10 expression in B cells is not fully understood yet. Tumor necrosis factor (TNF) is increased in allergic rhinitis (AR) patients. This study tests a hypothesis that TNF enhances histone deacetylase (HDAC)11 expression to inhibit the expression of IL-10 in B cells of AR patients. METHODS: Peripheral B cells were collected from healthy persons and patients with AR. The B cells were analyzed by immune assay and molecular biological approaches for the expression of IL-10. RESULTS: The expression of HDAC11 was higher in B cells of patients with AR than that in healthy persons. The expression of IL-10 in B cells was lower in AR patients than that in healthy subjects. The levels of HDAC11 in B cells were negatively correlated with the levels of IL-10. Exposure of B cells to TNF in the culture inhibited the expression of IL-10, in which HDAC11 played a critical role in the interference with the Il10 gene transcription. Inhibition of HDAC11 restored the IL-10 expression in B cells from AR patients and attenuated the experimental AR. CONCLUSION: TNF can suppress the expression of IL-10 in B cells via enhancing the expression of HDAC11. Inhibition of HDAC11 restores the IL-10 expression in B cells of AR subjects. HDAC11 may be a novel target for the treatment of AR.

Bcl2L12 Contributes to Th2-Biased Inflammation in the Intestinal Mucosa by Regulating CD4+ T Cell Activities.

The Th2-biased inflammation and immune deregulation play a critical role in the pathogenesis of ulcerative colitis (UC). Recent studies indicate that the Bcl2-like protein 12 (Bcl2L12) is associated with immune deregulation of UC. This study aims to investigate the role of Bcl2L12 in the induction of aberrant Th2-biased inflammation. In this study, peripheral blood samples were collected from patients with inflammatory bowel disease. The Th2 cell activities were analyzed by flow cytometry, real-time quantitative RT-PCR, and Western blotting. Mice with Bcl2L12-knockout CD4+ T cells were used in the experiments. The results showed that the expression of Bcl2L12 was detected in peripheral CD4+ T cells, which was significantly higher in UC patients than in healthy subjects. A positive correlation between the expression of Bcl2L12 and Th2 cytokines was detected in CD4+ T cells from UC patients. Naive CD4+ T cells with Bcl2L12 overexpression were prone to differentiate into Th2 cells. Mice with Bcl2L12 deficiency failed to induce the Th2-biased inflammation in the intestine. Bcl2L12 bound GATA3 to form a complex to enhance the binding between GATA3 and the Il4 promoter to enhance the expression of IL-4 in CD4+ T cells. CD4+ T cells with Bcl2L12 overexpression were resistant to apoptosis. In conclusion, the Bcl2L12 is a critical factor in the induction of aberrant Th2 polarization by upregulating Th2 responses and downregulating Th2 cell apoptosis. Bcl2L12 may be a novel therapeutic target in the management of the disorders with Th2-biased inflammation.

Vitamin D3 induces vitamin D receptor and HDAC11 binding to relieve the promoter of the tight junction proteins.

Intestinal epithelial barrier dysfunction and vitamin D (VitD)-deficiency play a critical role in a large number of diseases. The histone deacetylases (HDAC) are associated with a large number of immune diseases. This study tests a hypothesis that the interaction between VitD and HDAC is associated with the regulation of epithelial barrier functions. In this study, human intestinal epithelial cell line, T84 cells, was cultured into monolayers to be used as a model to test the epithelial barrier functions. We observed that in a VitD-deficient environment, the T84 monolayer barrier function was compromised. Exposure to calcitriol (the active form of VitD3) in the culture increased the expression of VitD receptor (VDR) in T84 cells. In a VitD-sufficient environment, VDR formed a complex with histone deacetylase-11 (HDAC11); the complex was markedly decreased in a VitD-deficient environment. We also observed that significantly more binding of HDAC11 to the promoter of the tight junction proteins inhibit the gene transcription activities of these loci in the VitD-deficient environment, which were abolished by the presence of calcitriol in the culture. In conclusion, the interaction between VDR and HDAC11 plays a crucial role in the maintenance of the epithelial barrier integrity.

Micro RNA-98 suppresses interleukin-10 in peripheral B cells in patient post-cardio transplantation.

The immune tolerance to the transplant heart survival is critical. Regulatory B cells are one of the major immune regulatory cell populations in the immune tolerance. Micro RNAs (miR) can regulate the activities of immune cells, such as the expression of interleukin (IL)-10 by B cells. This study tests a hypothesis that micro RNA (miR)-98 plays a role in the regulation of interleukin (IL)-10 expression in B cells (B10 cell) after heart transplantation. In this study, the peripheral blood samples were collected from patients before and after heart transplantation. The expression of miR-98 and IL-10 in B cells was assessed by real time RT-PCR. An allograft heart transplantation mouse model was developed. We observed that after heart transplantation, the frequency of peripheral B10 cell and the IL-10 mRNA levels in peripheral B cells were significantly decreased, the levels of miR-98 were increased in peripheral B cells and the serum levels of cortisol were increased in the patients. Treating naive B cells with cortisol in the culture suppressed the expression of IL-10 in B cells, which was abolished by knocking down the miR-98 gene. Administration with anti-miR-98, or cortisol inhibitor, or adoptive transfer with B10 cells, significantly enhanced the survival rate and time of mice received allograft heart transplantation. In conclusion, the enhancement of serum cortisol affects the immune tolerant feature of B cells, which can be attenuated by anti-miR-98-carrying liposomes.

Tumor necrosis factor suppresses interleukin 10 in peripheral B cells via upregulating Bcl2-like protein 12 in patients with inflammatory bowel disease.

The pathogenesis of the immune regulation dysfunction is unclear. Bcl2-like protein 12 (Bcl2L12) has immune suppression function. This study tests a hypothesis that tumor necrosis factor (TNF) increases Bcl2L12 to suppress the expression of interleukin (IL) 10 in peripheral B cells of patients with inflammatory bowel disease (IBD). In this study, peripheral blood samples were collected from IBD patients and healthy controls. B cells were isolated from the blood samples. The expression of IL-10 and Bcl2L12 in B cells was analyzed by quantitative reverse transcription polymerase chain reaction and Western blotting. We observed that the expression of Bcl2L12 in the peripheral B cells was higher in IBD patients than that in healthy controls. The IL-10 levels in B cells were negatively correlated with the expression of Bcl2L12. Exposure of B cells to TNF in the culture enhanced the expression of Bcl2L12. The Bcl2L12 mediated the effects of TNF on suppression of IL-10 in B cells. In conclusion, Bcl2L12 mediates the effects of TNF to suppress the expression of IL-10 in B cells. The data suggest that Bcl2L12 may be a therapeutic target for the treatment of IBD.

MicroRNA-98 plays a critical role in experimental myocarditis.

BACKGROUND AND AIMS: Myocarditis is inflammation in the heart; its pathogenesis is to be further investigated. Activities of micro RNAs (miR) are associated with immune inflammation. This study tests a hypothesis that miR-98 is involved in the development of myocarditis. METHODS: BALB/c mice were immunized with cardiac α-myosin heavy chain peptides (MyHC-α) to induce myocarditis. The effects of miR-98 on regulation of interleukin (IL)-10 were assessed by real time RT-PCR. RESULTS: Mice immunized with MyHC-α showed myocarditis and lower frequency of IL-10+ B cells (B10 cell) in the hearts. Expression of miR-98 was higher, IL-10 was lower, in B cells isolated from the mouse hearts with myocarditis, which was negatively correlated with each other. Exposure to tumor necrosis factor-α up regulated miR-98 expression in B cells. Over-expression of miR-98 suppressed IL-10 expression in B cells. Blocking miR-98 or adoptively transplanting B10 cells attenuated experimental myocarditis. CONCLUSIONS: miR-98 suppresses IL-10 expression in B cells in the heart, which plays an important role in myocarditis. MiR-98 may be a therapeutic target in the treatment of myocarditis.

Duodenal-Jejunal Bypass Surgery Ameliorates Glucose Homeostasis and Reduces Endoplasmic Reticulum Stress in the Liver Tissue in a Diabetic Rat Model.

BACKGROUND: Duodenal-jejunal bypass (DJB) has been shown to be an effective surgical treatment for type 2 diabetes mellitus (T2DM). However, the underlying mechanisms are poorly understood. Recently, accumulating evidences suggest that endoplasmic reticulum (ER) stress plays an important role in the development of insulin resistance in T2DM. The present study was designed to investigate the effect of DJB on glucose homeostasis, the ER stress state in the liver tissue, and the involving signaling independently of weight loss. METHODS: Thirty adult male T2DM Sprague-Dawley (SD) rats induced by high-fat diet and low dose of streptozotocin (STZ) were randomly divided into DJB and sham groups. Ten age-matched male SD rats were assigned as the control group. The parameters of body weight and calorie intake were measured at indicated time points. The glucose tolerance and insulin resistance were detected to evaluate the glucose homeostasis. Serum insulin was determined by enzyme-linked immunosorbent assay (ELISA). The markers of ER stress, the activity of c-Jun N-terminal kinase (JNK) and serine phosphorylation of insulin receptor substrate 1 (IRS-1) in the liver tissue, were determined by Western blotting. RESULTS: DJB induced significant improvements in glucose homeostasis and insulin sensitivity, but without weight loss. DJB improved the ER stress state indicated by decreased protein kinase RNA (PKR)-like ER protein kinase (PERK) and inositol-requiring enzyme 1 (IRE-1) phosphorylation in the liver tissue. The JNK activity and serine phosphorylation of IRS-1 in the liver tissue were significantly reduced after DJB. CONCLUSIONS: DJB ameliorates glucose homeostasis. Meanwhile, our study helps to reveal that the reduced hepatic ER stress and the decreased JNK activity may contribute to the improved glucose homeostasis after DJB.