Novel pH-sensitive gellan gum-ε-polylysine hydrogel microspheres for sulforaphene delivery.

BACKGROUND: This study aimed to improve the stability and utilization of sulforaphene (SFE) and to enhance the intestinal stability and pH-sensitive release of SFE in the gastrointestinal tract. To achieve this objective, calcium chloride (CaCl2) was used as a crosslinking agent to fabricate novel SFE-loaded gellan gum (GG)-ε-polylysine (ε-PL) pH-sensitive hydrogel microspheres by using the ionic crosslinking technique. RESULTS: The molecular docking results of GG, ε-PL, and SFE were good and occurred in the natural state. The loading efficiency (LE) of all samples was above 70%. According to the structural characterization results, GG and ε-PL successfully embedded SFE in a three-dimensional network structure through electrostatic interaction. The swelling characteristics and in vitro release results revealed that the microspheres were pH-sensitive, and SFE was mainly retained inside the hydrogel microsphere in the stomach, and subsequently released in the intestine. The result of cytotoxicity assay showed that the hydrogel microspheres were non-toxic and had an inhibitory effect on human colon cancer Caco-2 cells. CONCLUSION: Thus, the hydrogel microspheres could improve SFE stability and utilization and achieve the intestinal targeted delivery of SFE. © 2024 Society of Chemical Industry.

Imaging characteristics of ovarian sclerosing stromal tumor.

OBJECTIVES: This study was designed to evaluate the specific imaging features of ovarian sclerosing stromal tumor (SST), improve its accuracy as well as the specificity of imaging diagnosing, and prevent overestimation of malignancy to reduce unnecessary surgical procedures. METHODS: Eight patients with magnetic resonance imaging (MRI) and six with computed tomography (CT) images were analyzed in this retrospective observational study. All the cases were confirmed by postoperative pathological examination as those of ovarian SST. Imaging and pathological features were also evaluated. RESULTS: All the 14 masses displayed cystic and solid components with outer surface of tumors contained a capsular and complete smooth rim. Eight tumors of MRI exhibited "lake-island" sign on T2 weighted imaging (T2WI). Two of the 6 CT cases displayed a flaky calcification. One case showed as a multiloculated cystic mass with irregularly thickened septae and the tumor wall. The solid components in other 13 masses were comb- or wheel-like enhanced. After injection of contrast agent, the solid components in 8 cases (57.1%) appeared as early enhancement, whereas the other 6 cases (42.9%) appeared as progressive enhanced, and the cystic components of all the cases had no enhancement in the whole course. Vascular flow signals or/and marked enhancement of the blood vessels were found in 12 lesions (85.7%). Pathological examination demonstrated pseudolobule patterns, round to spindle shaped cells, collagenous areas, edematous hypocellular areas and prominent vasculatures. CONCLUSIONS: The results demonstrated that MRI with "lake-island" signs on T2WI and MRI/CT dynamic enhancement could potentially play a critical role in facilitating appropriate diagnosis preoperatively.

Sirolimus Can Increase the Disappearance Rate of Cardiac Rhabdomyomas Associated with Tuberous Sclerosis: A Prospective Cohort and Self-Controlled Case Series Study.

OBJECTIVES: To investigate the efficacy and safety of sirolimus in the treatment of cardiac rhabdomyomas associated with tuberous sclerosis complex and the specific benefits in different subgroups. STUDY DESIGN: The study was a prospective cohort and self-controlled case series study. Based on the prevalence of cardiac rhabdomyoma at different ages, we estimated the natural tumor disappearance rate. The subgroup analysis was done by Cox regression. Self-controlled case series method was used to assess the magnitude and duration of the drug effect. Adverse events were described. RESULTS: A total of 217 patients were included in the cohort study. Tumor disappearance rate was higher in younger age groups (hazard ratio = 0.99, P = .027) and female patients (hazard ratio = 2.08, P = .015). The age-adjusted incidence ratio showed that the disappearance of rhabdomyomas between 3 and 6 months was more related to sirolimus. Adverse events were observed 60 times in 42 of 217 children, mainly stomatitis. CONCLUSIONS: Sirolimus can increase the disappearance rate of cardiac rhabdomyoma in the tuberous sclerosis complex population. Efficacy varies by sex and age: female and younger patients have higher tumor disappearance rate. Sirolimus is well-tolerated.

Non-invasive investigation of early kidney damage in streptozotocin-induced diabetic rats by intravoxel incoherent motion diffusion-weighted (IVIM) MRI.

BACKGROUND: The current study investigated the performance of intravoxel incoherent motion diffusion (IVIM) technology in monitoring early renal injury in streptozotocin rats. METHODS: Forty-eight Sprague-Dawley (SD) rats were divided into a control group and a diabetic mellitus (DM) group. Six rats in each group were randomly selected for MR scans at four different time points (0, 4, 8, and 12 weeks). The IVIM-derived parameters (D, D*, f and ADC values) of the renal cortex (CO), outer and inner stripe of the outer medulla (OS, IS), and internal medulla (IM) were acquired. Changes in each IVIM-derived parameter over time were analyzed, and differences between the two groups at each point were assessed. The associations between the IVIM parameters and IV collagen expression, urine volume (UV), blood urea nitrogen (BUN), and serum creatinine (Scr) were investigated. RESULTS: The D and D* values of CO and the ADC values of CO, OS, IS and IM displayed significantly different trends between the two groups over time (P<0.05). In addition, significant correlations were discovered between the D* value of CO and UV and BUN (r=0.527, P=0.033; r=0.617, P=0.005), between the ADC value of IM and BUN (r=0.557, P=0.019) and between the f value of IM and BUN (r=0.527, P=0.033). No correlation was found between IVIM parameters and IV collagen expression and Scr. CONCLUSIONS: IVIM is a potential sensitive and noninvasive technology for the simultaneous assessment of early renal cortical and medullary injuries induced by diabetes.

Alterations of White Matter Connectivity in Preschool Children with Autism Spectrum Disorder.

Purpose To investigate the topologic architecture of white matter connectivity networks in preschool-aged children with a diagnosis of autism spectrum disorder (ASD) versus typical development (TD). Materials and Methods Forty-two participants were enrolled, including 21 preschool children with ASD (14 male children and seven female children; mean age, 4.56 years ± 0.97 [standard deviation]) and 21 children with TD (11 males and 10 females; mean age, 5.13 years ± 0.82). The diagnosis of ASD was determined according to the Diagnostic and Statistical Manual of Mental Disorders Global Assessment of Functioning scores (mean score, 8.00 ± 0.50). All participants underwent diffusion-tensor imaging (DTI) and T2-weighted imaging on a 3-T magnetic resonance system. A graph theoretical analysis was applied to investigate the topologic organization of the brain network including global and local topologic parameters. Statistical analysis was then performed for the comparison between the groups. Results Compared with the TD group, children with ASD demonstrated shortened characteristic path length (t1 = 0.536, t2 = 0.534, t3 = 0.523, t4 = 0.510, and t5 = 0.501; P < .05) and increased global efficiency (t1 = 0.499, t2 = 0.497, t3 = 0.486, t4 = 0.473, and t5 = 0.465; P < .05) and clustering coefficient (t1 = 0.673, t2 = 0.750, t3 = 0.757, t4 = 0.738, and t5 = 0.741; P < .05). Significant increases in nodal efficiency were mainly found in left pallidum (0.037 vs 0.032, respectively; P < .01) and right caudate nucleus (0.037 vs 0.032, respectively; P < .01) of the basal ganglia network. Conclusion Significantly altered patterns of global and local brain network topography may underlie the abnormal brain development in preschool children with ASD compared with those who have TD. The identification of altered structural connectivity in basal ganglia and paralimbic-limbic networks may point toward potential imaging biomarkers for preschool-age patients with ASD. © RSNA, 2018.

Role of quantitative intravoxel incoherent motion parameters in the preoperative diagnosis of nodal metastasis in patients with rectal carcinoma.

PURPOSE: To evaluate the diagnostic value of intravoxel incoherent motion imaging (IVIM) in differentiating metastatic and nonmetastatic lymph nodes in patients with rectal carcinoma. MATERIALS AND METHODS: In all, 68 patients with histologically proven rectal carcinoma underwent an IVIM sequence (b = 0, 25, 50, 75, 100, 150, 200, 400, 600, 800, 1000, 1200, 1500, and 2000 s/mm(2) ) on a 3.0T MRI scanner. The IVIM parameters (D, D*, f, and apparent diffusion coefficient [ADC] values) in metastatic and nonmetastatic lymph nodes were measured and calculated. Receiver-operating characteristic (ROC) analyses were conducted to determine the optimal thresholds, the sensitivities, and specificities for differentiation. RESULTS: Mean D, f, and ADC values of metastatic lymph nodes were significantly greater than those of the normal lymph nodes (P < 0.01), whereas the mean D* value of metastatic lymph node was statistically lower (P = 0.03). The AUC, sensitivity, specificity, and the cutoff value, respectively, for differentiating metastatic from nonmetastatic lymph nodes for D, D*, f, and ADC were as follows: D, 0.9460, 89.25%, 91.04%, and 1.14 × 10(-3) mm(2) /s; D*, 0.6930, 64.18%, 82.80%, and 7.02 × 10(-3) mm(2) /s; f, 0.7810, 92.47%, 55.22%, and 0.27%; ADC, 0.8970, 87.10%, 88.06%, and 0.80 × 10(-3) mm(2) /s. The ROC curves demonstrated that the area under the ROC (AUC) of the D, ADC, f, and D* values successively decreased, and D had the highest AUC, with D* values being lowest. CONCLUSION: An IVIM sequence may be helpful in diagnosing metastatic lymph nodes of rectal carcinoma. Average D and ADC values are more sensitive than f and D* values in this differentiation. J. MAGN. RESON. IMAGING 2016;44:1031-1039.

Reduced myelin content in bipolar disorder: A study of inhomogeneous magnetization transfer.

BACKGROUND: Previous neuroimaging and pathological studies have found myelin-related abnormalities in bipolar disorder (BD), which prompted the use of magnetic resonance (MR) imaging technology sensitive to neuropathological changes to explore its neuropathological basis. We holistically investigated alterations in myelin within BD patients by inhomogeneous magnetization transfer (ihMT), which is sensitive and specific to myelin content. METHODS: Thirty-one BD and 42 healthy controls (HC) were involved. Four MR metrics, i.e., ihMT ratio (ihMTR), pseudo-quantitative ihMT (qihMT), magnetization transfer ratio and pseudo-quantitative magnetization transfer (qMT), were compared between groups using analysis methods based on whole-brain voxel-level and white matter regions of interest (ROI), respectively. RESULTS: The voxel-wise analysis showed significantly inter-group differences of ihMTR and qihMT in the corpus callosum. The ROI-wise analysis showed that ihMTR, qihMT, and qMT values in BD group were significantly lower than that in HC group in the genu and body of corpus callosum, left anterior limb of the internal capsule, left anterior corona radiate, and bilateral cingulum (p < 0.001). And the qihMT in genu of corpus callosum and right cingulum were negatively correlated with depressive symptoms in BD group. LIMITATIONS: This study is based on cross-sectional data and the sample size is limited. CONCLUSION: These findings suggest the reduced myelin content of anterior midline structure in the bipolar patients, which might be a critical pathophysiological feature of BD.

Long-term safety and influence on growth in patients receiving sirolimus: a pooled analysis.

BACKGROUND: Sirolimus is increasingly utilized in treating diseases associated with mTOR pathway overactivation. Despite its potential, the lack of evidence regarding its long-term safety across all age groups, particularly in pediatric patients, has limited its further application. This study aims to assess the long-term safety of sirolimus, with a specific focus on its impact on growth patterns in pediatric patients. METHODS: This pooled analysis inlcudes two prospective cohort studies spanning 10 years, including 1,738 participants (aged 5 days to 69 years) diagnosed with tuberous sclerosis and/or lymphangioleiomyomatosis. All participants were mTOR inhibitor-naive and received 1 mg/m²/day of sirolimus, with dose adjustments during a two-week titration period to maintain trough blood concentrations between 5 and 10 ng/ml (maximum dose 2 mg). Indicators of physical growth, hematopoietic, liver, renal function, and blood lipid levels were all primary outcomes and were analyzed. The adverse events and related management were also recorded. RESULTS: Sirolimus administration did not lead to deviations from normal growth ranges, but higher doses exhibited a positive association with Z-scores exceeding 2 SD in height, weight, and BMI. Transient elevations in red blood cell and white blood cell counts, along with hyperlipidemia, were primarily observed within the first year of treatment. Other measured parameters remained largely unchanged, displaying only weak correlations with drug use. Stomatitis is the most common adverse event (920/1738, 52.9%). In adult females, menstrual disorders were observed in 48.5% (112/217). CONCLUSIONS: Sirolimus's long-term administration is not associated with adverse effects on children's physical growth pattern, nor significant alterations in hematopoietic, liver, renal function, or lipid levels. A potential dose-dependent influence on growth merits further exploration. TRIAL REGISTRATION: Pediatric patients: Chinese clinical trial registry, No. ChiCTR-OOB-15,006,535. Adult patients: ClinicalTrials, No. NCT03193892.

Preliminary Feasibility Study on Diffusion Kurtosis Imaging to Monitor the Early Functional Alterations of Kidneys in Streptozocin-Induced Diabetic Rats.

RATIONALE AND OBJECTIVES: The aim of this study was to investigate the potential of diffusion kurtosis imaging (DKI) to assess the early renal functional undulation of diabetic mellitus (DM). MATERIALS AND METHODS: Fifty-seven Sprague-Dawley (SD) rats were randomly divided into two groups and eventually 48 rats were included in this study: the normal control (CON) group and diabetic mellitus (DM) group. Weeks 0, 4, 8, and 12 after the diabetes model was successfully established, all the rats were scanned on the 3.0T MRI. The DKI derived parameters of renal parenchyma, including fractional anisotropy (FAco, FAme), mean diffusivity (MDco, MDme), and mean kurtosis (MKco, MKme) were measured. Their alteration over time was analyzed and then correlated with urine volume (UV), blood urea nitrogen (BUN), and serum creatinine (Scr) using Pearson correlation analysis. Finally, hematoxylin and eosin (H&E) staining was performed on the kidneys of the two groups. RESULT: There was a decreasing trend in FA, MK, and MD values over time in diabetic rats. Also, the gradually worsening histological damage of kidneys was noted over time in diabetic rats. The cortical FA and MK values and medullary FA, MK and MD values of diabetic rats were significantly lower than those of controls at most time points after DM induction. In addition, negative correlations were revealed between the BUN and FAco (r = -0.43, p = 0.03) or FAme value (r = -0.49, p = 0.01). The cortical MK value was moderately correlated with UV (r = -0.46, p = 0.03) and BUN (r = -0.55, p = 0.01). CONCLUSION: The preliminary findings suggest that DKI might be an effective and sensitive tool to assess the early changes of renal function impairment in diabetic rats. The FA values of the cortex and medulla and the MK value of the cortex are sensitive markers in detecting renal injury in diabetic rats.

Minimal gene set discovery in single-cell mRNA-seq datasets with ActiveSVM.

Sequencing costs currently prohibit the application of single-cell mRNA-seq to many biological and clinical analyses. Targeted single-cell mRNA-sequencing reduces sequencing costs by profiling reduced gene sets that capture biological information with a minimal number of genes. Here we introduce an active learning method that identifies minimal but highly informative gene sets that enable the identification of cell types, physiological states and genetic perturbations in single-cell data using a small number of genes. Our active feature selection procedure generates minimal gene sets from single-cell data by employing an active support vector machine (ActiveSVM) classifier. We demonstrate that ActiveSVM feature selection identifies gene sets that enable ~90% cell-type classification accuracy across, for example, cell atlas and disease-characterization datasets. The discovery of small but highly informative gene sets should enable reductions in the number of measurements necessary for application of single-cell mRNA-seq to clinical tests, therapeutic discovery and genetic screens.

ERK1/2 Signalling Pathway Regulates Tubulin-Binding Cofactor B Expression and Affects Astrocyte Process Formation after Acute Foetal Alcohol Exposure.

Foetal alcohol spectrum disorders (FASDs) are a spectrum of neurological disorders whose neurological symptoms, besides the neuronal damage caused by alcohol, may also be associated with neuroglial damage. Tubulin-binding cofactor B (TBCB) may be involved in the pathogenesis of FASD. To understand the mechanism and provide new insights into the pathogenesis of FASD, acute foetal alcohol exposure model on astrocytes was established and the interference experiments were carried out. First, after alcohol exposure, the nascent astrocyte processes were reduced or lost, accompanied by the absence of TBCB expression and the disruption of microtubules (MTs) in processes. Subsequently, TBCB was silenced with siRNA. It was severely reduced or lost in nascent astrocyte processes, with a dramatic reduction in astrocyte processes, indicating that TBCB plays a vital role in astrocyte process formation. Finally, the regulating mechanism was studied and it was found that the extracellular signal-regulated protease 1/2 (ERK1/2) signalling pathway was one of the main pathways regulating TBCB expression in astrocytes after alcohol injury. In summary, after acute foetal alcohol exposure, the decreased TBCB in nascent astrocyte processes, regulated by the ERK1/2 signalling pathway, was the main factor leading to the disorder of astrocyte process formation, which could contribute to the neurological symptoms of FASD.

Decreased tubulin-binding cofactor B was involved in the formation disorder of nascent astrocyte processes by regulating microtubule plus-end growth through binding with end-binding proteins 1 and 3 after chronic alcohol exposure.

Fetal alcohol syndrome (FAS) is a neurological disease caused by excessive drinking during pregnancy and characterized by congenital abnormalities in the structure and function of the fetal brain. This study was proposed to provide new insights into the pathogenesis of FAS by revealing the possible mechanisms of alcohol-induced astrocyte injury. First, a chronic alcohol exposure model of astrocytes was established, and the formation disorder was found in astrocyte processes where tubulin-binding cofactor B (TBCB) was decreased or lost, accompanied by disorganized microtubules (MT). Second, to understand the relationship between TBCB reduction and the formation disorder of astrocyte processes, TBCB was silenced or overexpressed. It caused astrocyte processes to retract or lose after silencing, while the processes increased with expending basal part and obtuse tips after overexpressing. It confirmed that TBCB was one of the critical factors for the formation of astrocyte processes through regulating MT plus-end and provided a new view on the pathogenesis of FAS. Third, to explore the mechanism of TBCB regulating MT plus-ends, we first proved end-binding proteins 1 and 3 (EB1/3) were bound at MT plus-ends in astrocytes. Then, through interference experiments, we found that both EB1 and EB3, which formed in heterodimers, were necessary to mediate TBCB binding to MT plus-ends and thus regulated the formation of astrocyte processes. Finally, the regulatory mechanism was studied and the ERK1/2 signaling pathway was found as one of the main pathways regulating the expression of TBCB in astrocytes after alcohol injury.

Effects of resveratrol on lipid and protein co-oxidation in fish oil-enriched whey protein isolate emulsions.

In this study, the impact of resveratrol (RES) on co-oxidation of lipid and protein in a fish oil-fortified whey protein isolate (WPI) emulsion was investigated. Oil-in-water (O/W) emulsions containing 1% fish oil, 6 mg/mL of WPI and RES (0.08 ~ 2 mM) were oxidatively stressed using a Fenton system at 25 °C for 24 h. The incorporation of RES significantly suppressed lipid oxidation (TBARS) and protein carbonylation. Oxidation-induced decrease on protein sulfhydryl content and surface hydrophobicity were partially attenuated by RES, but protein tryptophan fluorescence was further decreased with the increased concentration of RES. Visualization of protein patterns and MDA-bound protein suggested that RES is capable of inhibiting protein modification induced by secondary products of lipid oxidation. Significant decrease in protein digestibility under oxidizing condition was also mitigated by RES. Our study contributes to the exploration of complicated interactions between oxidized lipids and proteins when phenolic compounds are present.

Coordinated DNA Methylation and Gene Expression Data for Identification of the Critical Genes Associated with Childhood Atopic Asthma.

Asthma is a chronic inflammatory disorder of airways that involves in many cells and factors. This study aimed to screen critical genes and miRNAs involved in childhood atopic asthma. DNA methylation and gene expression data (access numbers GSE65163 and GSE65204) were downloaded from Gene Expression Omnibus (GEO) database, which included 72 atopic asthmatic subject samples and 69 healthy samples. The differentially expressed genes (DEGs) with DNA methylation changes were identified, followed by Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Gene coexpression network and miRNA-target gene regulatory networks were then constructed. Besides, we screened critical drug molecules that have high correlation with atopic asthma in children. A total of 146 critical DEGs with DNA methylation changes were screened from atopic asthmatic samples compared with healthy control samples. GO and KEGG pathway enrichment analysis showed that the critical genes were mainly related to 20 GO terms and 13 KEGG pathways. In the coexpression network, tumor necrosis factor (TNF) and major histocompatibility complex, class II, DP alpha 1 (HLA-DPA1) were identified that were significantly related to immune response process. Analysis of miRNA-target gene network showed that hsa-miR-148b had the highest number of target genes(degree = 21). Besides, we found that Alsterpaullone had a correlation value closest to -1 (correlation = -0.884, p = 0.0031), which indicated that the agent might be considered as a potential agent that antagonized to asthma. The dysregulation of TNF, HLA-DPA1, and miR-148b might be related to the immune response of childhood atopic asthma.

Transaminitis in a Three-year-old Boy with Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is a fatal X-linked genetic disease of the neuromuscular system and is the most serious type of muscular dystrophy in humans. The disease is characterized by progressive muscular atrophy and a poor prognosis. The incidence rate is 1/3500, and symptoms appear at age of 5 years-old. Some patients present with abnormal aminotransferases as the first symptom. In addition to the clinical characteristics and genetic history, electromyography examination, muscle biopsy, serum enzyme examination, and measures of creatine kinase (CK), CK isoenzyme, and serum lactate dehydrogenase are important features of auxiliary examination. Clinicians who encounter unknown causes of transaminitis should consider the possibility of DMD. We describe here a 3 year-old pediatric patient with increased aminotransferases who had elevated CK and a family genetic history but without liver damage on computed tomography. He was suspected as having inherited the disorder and was finally diagnosed as having DMD by next-generation sequencing.

Sirolimus improves seizure control in pediatric patients with tuberous sclerosis: A prospective cohort study.

PURPOSE: This study aimed to analyze the therapeutic effect of sirolimus on seizures in pediatric patients with tuberous sclerosis. METHODS: We first compared the efficacy of controlling seizures in all patients after they had taken sirolimus for one year, and then we performed a subgroup analysis based on whether the administered antiepileptic drugs were changed to determine whether the efficacy was associated with changes of antiepileptic drugs. RESULTS: A total of 91 eligible children were enrolled. The response rate was 78.0 % (71/91), and 47.2 % (43/91) of all patients were became seizure-free. The improvement in seizure control before and after treatment with sirolimus was significant (p < 0.001). In the AEDs unaltered group, 34 were responders (34/45, 75.6 %, 95 % CI 17.4-88.3), of which 24 were seizure-free (24/34, 70.6 %). In the AEDs-altered group, 37 were responders (37/46, 80.4 %, 95 % CI 56.7-88.1), of which 19 were seizure-free (19/37, 51.4 %). There was no significant difference between the two groups for reductions in rate of seizure frequency (p = 0.308). In the patients with refractory epilepsy, treatment with sirolimus was also effective (p = 0.01). Logistic regression analysis showed that age was an important factor affecting outcome of epilepsy (p = 0.003, 95 % CI 2.05-38.31). No Grade 3 or 4 adverse events were noted during the follow-up. CONCLUSIONS: Sirolimus has a significant effect on seizures associated with tuberous sclerosis complex (TSC), with no or only moderate adverse events after long-term administration. Sirolimus could be used as the first-line medication for pediatric patients with TSC-associated epilepsy.

Influence of malondialdehyde-induced modifications on physicochemical and digestibility characteristics of whey protein isolate.

Impacts of lipid oxidation product malondialdehyde (MDA) on the properties of whey protein isolate (WPI) were investigated in this study. The incorporation of MDA into WPI promoted the formation of protein carbonyls, with the significant loss of protein sulfhydryls, impaired intrinsic fluorescence, and increased protein surface hydrophobicity. The visualized band profiles revealed by gel electrophoresis and immunoblotting suggested that WPI's main components ß-lactoglobulin and α-lactalbumin were the targets of MDA, and the derivatives of MDA were involved in protein cross-linking and aggregation at higher molecular weights. Abnormal protein aggregation was further confirmed by scanning electron microscopy analysis of the surface microstructure of MDA-modified WPI. Finally, in vitro digestibility assay indicated that the modification of MDA reduced WPI's susceptibility to digestive enzymes. The present study demonstrated that the contribution of MDA to protein modification in dairy products can be substantial in complex foodstuffs composed of lipids and proteins. PRACTICAL APPLICATIONS: The present work enhanced our knowledge on the remarkable susceptibility of dairy product WPI to lipid oxidation product MDA. With the trend of application of highly unsaturated fatty acids such as fish oil or alga oils as functional ingredients in dairy products, it is obvious that apart from monitoring lipid oxidation products, the resultant changes in dietary proteins deserve more attention. The food industry must be aware of the importance of appropriate preventive measures in minimizing the negative effects of lipid oxidation products on dairy products.

Intravoxel incoherent motion (IVIM) at 3.0 T: evaluation of early renal function changes in type 2 diabetic patients.

PURPOSE: The purpose of this study was to evaluate the utility of intravoxel incoherent motion diffusion-weighted imaging (IVIM DWI) parameters in identifying early renal function changes in diabetics. METHODS: A total of 40 patients with type 2 diabetes mellitus and 20 healthy control subjects underwent multiple b value DWI. The diabetic patients were stratified into two groups based on albuminuria category: NAU (normal to mildly increased albuminuria; ACR < 30 mg/g) and MAU (moderately increased albuminuria; 30 ≤ ACR < 300 mg/g). The mean cortical and medullary IVIM parameters (D, D*, f, and ADC) were calculated and compared among the different groups, and the correlation of ACR and eGFR was also calculated. RESULTS: The present study revealed the limited water molecule diffusion and hyperperfusion of renal cortex and medulla in diabetic patients before proteinuria detection. Mean cortical and medullary D values negatively correlated with the ACR values in diabetics with 30 ≤ ACR < 300 mg/g, whereas no correlation was found between ACR values and other IVIM parameters. CONCLUSION: IVIM DWI might be helpful in noninvasively identifying early-stage DN. The IVIM parametric values are more sensitive than the ACR in detecting early-stage kidney changes.

RNF138 confers cisplatin resistance in gastric cancer cells via activating Chk1 signaling pathway.

Chemotherapy resistance represents a major issue associated with gastric cancer (GC) treatment, and arises through multiple mechanisms, including modulation of the cell-cycle check point. Several ubiquitin kinases, including RING finger protein 138 (RNF138), have been reported to mediate the G2/M phase arrest. In this study, we investigated the role of RNF138 in the development of cisplatin resistance of two GC cell lines. We show that RNF138 levels are higher in cisplatin-resistant cell lines, compared with cisplatin-sensitive cells, and RNF138 expression was elevated during drug withdrawal following the cisplatin treatment. Using gene overexpression and silencing, we analyzed the impact of altering RNF138 level on GC cell viability, apoptosis, and cell cycle phenotypes in two isogenic cisplatin-sensitive and resistant cell lines. We show that RNF138 overexpression increased GC cell viability, decreased apoptosis and delayed cell cycle progression in the cisplatin-sensitive GC cells. Conversely, RNF138 silencing produced opposite phenotypes in the cisplatin-resistant cells. Moreover, RNF138-dependent phosphorylation of Chk1 was seen in GC cells, indicating a novel connection between cisplatin-induced DNA damage and apoptosis. Collectively, these data suggest that RNF138 modulates the cisplatin resistance in the GC cells, thus serving as a potential drug target to challenge chemotherapy failure. In addition, RNF138 can also be used as a marker to monitor the development of cisplatin resistance in GC treatment.

Two de novo variations identified by massively parallel sequencing in 13 Chinese families with children diagnosed with autism spectrum disorder.

Autism spectrum disorder (ASD) is a genetically heterogeneous neurodevelopmental disorder characterized by impairments in social interaction and communication, and by restricted and repetitive behaviors. The genetic architecture of ASD has been elucidated, including chromosomal rearrangements, de novo or inherited rare variants, and copy number variants. However, the genetic mechanism of Chinese families with ASD children is explored rarely. To identify genetic pathogenesis, we performed massively parallel sequencing on 13 Chinese ASD trio families, and found two de novo variations. The novel de novo splice alteration c.664 + 2T > G in the DEAF1 gene and the novel de novo missense mutation c.95 C > T in the AADAT gene associated with ASD may be important clues for exploring the etiology of this disorder.