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- ArticleElbehairy MM, Abdelnasser HY, Hanafi RS, Hassanein SI, Gad MZ.Steroids. 2021 05;169:108825.INTRODUCTION: Vitamin D deficiency has been linked to cardiovascular pathologies including acute coronary syndrome (ACS). Polymorphisms in vitamin D associated genes have been confounding to vitamin D serum levels and pathological predispositions. 7-hydrocholesterol is a common precursor in cholesterol and vitamin D synthesis. DHCR7/NADSYN1 genetic locus expresses 7-hydrocholesterol reductase (DHCR7), an enzyme that recruits 7-hydrocholesterol in cholesterol biosynthesis, and NAD synthetase 1 (NADSYN1), which participates in the hydroxylation of 25 hydroxyvitamin D.
AIM: This study aims to correlate two polymorphisms in the DHCR7/NADSYN1 genetic locus with levels of circulatory vitamin D and the presentation of ACS in an Egyptian population.
METHODS: In a case control study, 189 ACS patients and 106 healthy control subjects were genotyped for SNPs rs11606033 of the DHCR7 gene and rs2276360 of the NADSYN1 gene using the amplification-refractory mutation system (ARMS). The levels of 25(OH)D2 and 25(OH)D3 were measured using an in-house developed and validated ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) based protocol.
RESULTS: ACS patients have significantly lower levels of circulating vitamin D in comparison to healthy controls. Allele A of the DHCR7 polymorphism was found to correlate with serum vitamin D deficiency and incidence of ACS classes: NSTEMI, STEMI and unstable angina, when compared to allele G. On the other hand, the NADSYN1 polymorphism rs2276360 correlated with serum 25(OH)D3 deficiency. Yet, no significant correlation was found with incidences of ACS.
CONCLUSION: We conclude that rs11606033, which is an intronic SNP between exon 4 and exon 5 of the DHCR7 gene, influences vitamin D serum abundance and more importantly ACS incidence. - ArticleLavalley CA, Hakimi N, Taylor S, Kuplicki R, Forthman KL, Stewart JL, Paulus MP, Khalsa SS, Smith R.Biol Psychol. 2024 May 31;191:108825.Recent Bayesian theories of interoception suggest that perception of bodily states rests upon a precision-weighted integration of afferent signals and prior beliefs. In a previous study, we fit a computational model of perception to behavior on a heartbeat tapping task to test whether aberrant precision-weighting could explain misestimation of cardiac states in psychopathology. We found that, during an interoceptive perturbation designed to amplify afferent signal precision (inspiratory breath-holding), healthy individuals increased the precision-weighting assigned to ascending cardiac signals (relative to resting conditions), while individuals with anxiety, depression, substance use disorders, and/or eating disorders did not. In this pre-registered study, we aimed to replicate and extend our prior findings in a new transdiagnostic patient sample (N = 285) similar to the one in the original study. As expected, patients in this new sample were also unable to adjust beliefs about the precision of cardiac signals - preventing the ability to accurately perceive changes in their cardiac state. Follow-up analyses combining samples from the previous and current study (N = 719) also afforded power to identify group differences between narrower diagnostic categories, and to examine predictive accuracy when logistic regression models were trained on one sample and tested on the other. With this confirmatory evidence in place, future studies should examine the utility of interceptive precision measures in predicting treatment outcomes and test whether these computational mechanisms might represent novel therapeutic targets.
- ArticleWeinschenk C, Ghanekar S, Stakes K, Quiat A, Kessler RM, Lee T.Data Brief. 2023 Feb;46:108825.The fire modeling community currently lacks full-scale experi- mental data from fires in residential-style structures with heat- ing, ventilation, and air conditioning (HVAC) systems. Further, there is an absence of data quantifying the generation of H2O due to combustion and the subsequent transport of those gases with a structure. Propane gas burner fire experiments were con- ducted in a purpose-built two-story structure instrumented to measure temperature, pressure, velocity, and gas concentrations. Experiments were conducted to assess heat and gas species trans- fer due to HVAC operating status (off vs. on), fire location and heat release rate, and bedroom door position (open vs. closed).
- ArticleFaghfouri AH, Baradaran B, Khabbazi A, Abdoli Shadbad M, Papi S, Faghfuri E, Khajebishak Y, Rahmani S, Tolou Hayat P, Alipour B.Int Immunopharmacol. 2022 Aug;109:108825.BACKGROUND: Overproduction of NLRP3 inflammasome complex is one of the causes of Behcet's disease's (BD) auto-inflammatory nature. The aim of current study was to examine the effect of zinc supplementation on NLRP3 inflammasome expression; as well as clinical manifestations of BD.
METHODS: In this double-blind parallel placebo-controlled randomized clinical trial, 50 BD patients were randomly allocated into either zinc gluconate (30 mg/day elemental zinc) or placebo groups for 12 weeks. The mRNA expression of NLRP3 and caspase-1 in the leukocytes, serum level of zinc and IL-1β, anthropometric measures, and clinical manifestations of patients were collected at pre- and post-intervention phase. The Iranian Behçet's disease dynamic activity measure (IBDDAM) was scored to measure the treatment effect using the calculation of number needed to treat (NNT). Analysis of covariance was performed to obtain the corresponding effect sizes.
RESULTS: Zinc gluconate led to a significant improvement in genital ulcer (P = 0.019). Zinc supplementation decreased NLRP3 and caspase-1 genes expression compared with placebo group (baseline-adjusted P-value = 0.046 for NLRP3 and P-value = 0.003 for caspase-1), even after adjustment for the effect of confounding factors (baseline- and confounders-adjusted P-value = 0.032 for NLRP3 and P-value = 0.004 for caspase-1). Baseline and confounders adjusted effect size demonstrated that zinc was effective in reducing the serum level of IL-1β (P = 0.046). The NNT [95 %CI] for the rate of IBDDAM improvement was 3 [1.7-8.5].
CONCLUSIONS: Zinc gluconate supplementation (30 mg/day) for a 3-month period can be considered as an adjuvant therapy in alleviating inflammation and genital ulcer among BD patients. - ArticleLiu K, Santos DA, Hussmann JA, Wang Y, Sutter BM, Weissman JS, Tu BP.Cell Rep. 2021 03 09;34(10):108825.N6-methyladenosine (m6A) is a conserved ribonucleoside modification that regulates many facets of RNA metabolism. Using quantitative mass spectrometry, we find that the universally conserved tandem adenosines at the 3' end of 18S rRNA, thought to be constitutively di-methylated (m62A), are also mono-methylated (m6A). Although present at substoichiometric amounts, m6A at these positions increases significantly in response to sulfur starvation in yeast cells and mammalian cell lines. Combining yeast genetics and ribosome profiling, we provide evidence to suggest that m6A-bearing ribosomes carry out translation distinctly from m62A-bearing ribosomes, featuring a striking specificity for sulfur metabolism genes. Our work thus reveals methylation multiplicity as a mechanism to regulate translation.
- ArticleSun Y, Ayoma Marasinghe S, Hou J, Wang P, Zhang Q, Sundell J.Environ Int. 2024 Jun 19;190:108825.There has been an increased concern on indoor air quality (IAQ) in residences since the majority of individuals' time is mainly spent indoors. We inspected and measured indoor environmental parameters in 399 homes in northeast China in order to study IAQ. We systematically measured multilevel environmental parameters (physical, chemical, and biological) in children's bedrooms during all seasons. The results indicated that the median values for indoor temperature, relative humidity, total volatile organic compounds (TVOC), and formaldehyde concentrations throughout the year were within the Chinese national standards. However, the median carbon dioxide concentrations exceeded 1000 ppm during spring, autumn, and winter. In the same seasons, the air change rate (ACR) was below the minimum required level of 0.5 h-1. Di-2-ethylhexyl phthalate (DEHP), di-n-butyl phthalate (DnBP), and di-isobutyl phthalate (DiBP) were predominantly detected in settled dust, displaying median concentrations of 126.9, 41.5, and 16.3 μg/g, respectively. Notably, phthalate concentrations were significantly higher in urban houses as compared to rural houses. Furthermore, median concentrations of Dermatophagoides farinae (Der f) and endotoxin were 689.4 ng/g and 3689.1 EU/g, respectively, trending higher in winter than summer. There was a negative correlation between ACR and chemical pollutants (TVOC, formaldehyde, and DiBP). In conclusion, northeast Chinese homes had poor indoor air quality with ubiquitous exposure to modern chemical compounds and insufficient ventilation.
- ArticleLu Y, Liu J, Li B, Wang H, Wang F, Wang S, Wu H, Han H, Hua Y.iScience. 2024 Feb 16;27(2):108825.In the mammalian cochlea, moderate acoustic overexposure leads to loss of ribbon-type synapse between the inner hair cell (IHC) and its postsynaptic spiral ganglion neuron (SGN), causing a reduced dynamic range of hearing but not a permanent threshold elevation. A prevailing view is that such ribbon loss (known as synaptopathy) selectively impacts the low-spontaneous-rate and high-threshold SGN fibers contacting predominantly the modiolar IHC face. However, the spatial pattern of synaptopathy remains scarcely characterized in the most sensitive mid-cochlear region, where two morphological subtypes of IHC with distinct ribbon size gradients coexist. Here, we used volume electron microscopy to investigate noise exposure-related changes in the mouse IHCs with and without ribbon loss. Our quantifications reveal that IHC subtypes differ in the worst-hit area of synaptopathy. Moreover, we show relative enrichment of mitochondria in the surviving SGN terminals, providing key experimental evidence for the long-proposed role of SGN-terminal mitochondria in synaptic vulnerability.
- ArticleHomolya Á, Jedlóczki I, Kónya-Ábrahám A, Somsák L, Tóth M, Juhász L.Carbohydr Res. 2023 Jul;529:108825.Azidohydroxylation of 1-carbamoyl, 1-methoxycarbonyl and 1-cyano substituted d-lyxo and d-arabino configured O-peracylated glycals was studied and the reaction conditions were optimized. Under these conditions (3 equiv. NaN3/2 equiv. PIFA/0.3 equiv. TEMPO/50 equiv. H2O/dry DCM/0 °C/Ar) the expected 3-azido-3-deoxy ulopyranosonic acid derivatives were isolated in good yield with α-d-galacto configuration exclusively from the reaction of the 1-carbamoyl and 1-methoxycarbonyl substituted d-lyxo configured O-peracetylated glycals, while the transformation of the 1-cyano derivative gave a 2,3-vicinal diazide in low yield. The 1-carbamoyl d-arabino configured O-perbenzoylated glycal gave a mixture of α-d-gluco and α-d-manno configured azidohydroxylated products with d-gluco preference. The analogous 1-methoxycarbonyl derivative gave an inseparable product mixture and no transformation was detected with the respective 1-cyano glycal.
- ArticleLi D, Li Z, Yang Y, Zeng X, Li Y, Du X, Zhu X.Environ Res. 2020 01;180:108825.Chemical contamination in the environment is known to cause abnormal circular RNA (circRNA) expression through multiple exposure routes; yet, the underlying molecular mechanisms remain unclear. Non-coding RNAs (ncRNAs), especially circRNAs, play important roles in epigenetic regulation and disease pathogenesis; however, few studies have examined the function of circRNAs in chemical contamination-induced diseases. CircRNAs are covalently closed continuous loops that do not possess 5' and 3' ends, increasing their structural stability and limiting degradation by exoribonucleases. In addition, environmental chemical exposure-related diseases are often accompanied by aberrant expression of specific circRNAs and those circRNAs are often detected in tissues and body fluids. Based on these characteristics, circRNAs may serve as candidate biomarkers for the diagnosis of diseases related to environmental chemical exposure. Here, we review the generation and function of circRNAs, and the possible molecular mechanisms underlying the regulation of environmental chemical exposure-related disorders by circRNAs. This is the first comprehensive review of the relationship between environmental chemical exposure and circRNAs in chemical exposure-induced diseases.
- ArticleCristea G, Voica C, Feher I, Puscas R, Magdas DA.Meat Sci. 2022 Jul;189:108825.In this study 93 pork meat samples (tenderloin) were analyzed via isotope ratios mass spectrometry (δ2H, δ18O, δ13C) and inductively coupled plasma - Mass spectrometry (55 elements). The meat samples are coming from Romania and abroad. Those from Romania are originating from conventional farms and yard rearing system. The analytical results in conjunction with linear discriminant analysis (LDA) and artificial neural networks (ANNs) were used to assess: The geographical origin, and animal diet. The most powerful markers which could differentiate pork meat samples concerning the geographical origin were δ18O, terbium, and tin. The results of chemometric models showed that, along with 13C signature, rubidium concentration, and a few rare earth-elements (lanthanum, and cerium) were efficient to discriminate animal diet in a percent of 97.8% (initial classification) and 94.6% (cross-validation), respectively. Some of predictors for feeding regime differentiation by using LDA were identified also to be the best markers to distinguish corn-based diet by using ANNs (δ13C, Rb, La).
- ArticleLasagni Vitar RM, Bonelli F, Atay A, Triani F, Fonteyne P, Di Simone E, Rama P, Mondino A, Ferrari G.Exp Eye Res. 2021 11;212:108825.PURPOSE: to assess the effect of topical administration of the Neurokin-1 receptor (NK1R) antagonist Fosaprepitant in a pre-clinical model of ocular Graft-versus-Host disease (GVHD).
METHODS: BALB/c mice were pre-conditioned by myeloablative total body irradiation and subjected to allogeneic bone marrow transplantation and mature T cell infusion (BM + T). BM-transplanted mice (BM) were used as controls. Ocular GVHD was specifically assessed by quantifying corneal epithelial damage, tear secretion, blepharitis and phimosis, 3 times/week for 28 days post-transplantation. A group of BM + T mice received Fosaprepitant 10 mg/mL, 6 times/day, topically, from day 7-29 after transplantation. After sacrifice, the expression of NK1R, CD45, CD3, and CXCL10 was quantified in the cornea, conjunctiva, and lacrimal gland by immunohistochemistry.
RESULTS: BM + T mice developed corneal epithelial damage (day 0-29, p < 0.001), blepharitis (day 0-29, p < 0.001), and phimosis (day 0-29, p < 0.01), and experienced decreased tear secretion (day 21, p < 0.01) compared to controls. NK1R was found upregulated in corneal epithelium (p < 0.01) and lacrimal gland (p < 0.01) of BM + T mice. Fosaprepitant administration significantly reduced corneal epithelial damage (p < 0.05), CD45+ (p < 0.05) and CD3+ (p < 0.01) immune cell infiltration in the cornea and conjunctiva (p < 0.001 and p < 0.001, respectively). In addition, Fosaprepitant reduced the expression of CXCL10 in the cornea (p < 0.05) and in the lacrimal gland (p < 0.05).
CONCLUSIONS: Our results suggest that NK1R represents a novel druggable pathway for the therapy of ocular GVHD. - ArticleGuo Y, Huang L, Bi K, Xu Q, Bu Z, Wang F, Sun E.Vet Microbiol. 2020 Sep;248:108825.Bluetongue (BT) is an arbovirus-borne disease of ruminants caused by bluetongue virus (BTV) that has the potential to have a serious economic impact. Currently available commercial vaccines include attenuated vaccines and inactivated vaccines, both of which have achieved great success in the prevention and control of BTV. However, these vaccines cannot distinguish between infected animals and immunized animals. To control outbreaks of BTV, the development of labeled vaccines is urgently needed. In this study, we used the plasmid-based reverse genetics system (RGS) of BTV to rescue four recombinant viruses in which HA (influenza hemagglutinin) tags were inserted at different sites of VP2. In vitro, the recombinant tagged viruses exhibited morphologies, plaque, and growth kinetics similar to the parental BTV-16, and expressed both VP2 and HA tag. Subsequently, the selected recombinant tagged viruses were prepared as inactivated vaccines to immunize IFNAR(-/-) mice and sheep, and serological detection results of anti-HA antibody provided discriminative detection. In summary, we used plasmid-based RGS to rescue BTV recombinant viruses with HA tags inserted into VP2, and detected several sites on VP2 that can accommodate HA tags. Some of the recombinant tagged viruses have potential to be developed into distinctive inactivated vaccines.
- ArticleShu Z, Huang YC, Palmer WH, Tamori Y, Xie G, Wang H, Liu N, Deng WM.Oncotarget. 2017 Dec 12;8(65):108825-108839.Despite their emergence as an important class of noncoding RNAs involved in cancer cell transformation, invasion, and migration, the precise role of microRNAs (miRNAs) in tumorigenesis remains elusive. To gain insights into how miRNAs contribute to primary tumor formation, we conducted an RNA sequencing (RNA-Seq) analysis of Drosophila wing disc epithelial tumors induced by knockdown of a neoplastic tumor-suppressor gene (nTSG) lethal giant larvae (lgl), combined with overexpression of an active form of oncogene Ras (RasV12 ), and identified 51 mature miRNAs that changed significantly in tumorous discs. Followed by in vivo tumor enhancer and suppressor screens in sensitized genetic backgrounds, we identified 10 tumor-enhancing (TE) miRNAs and 11 tumor-suppressing (TS) miRNAs that contributed to the nTSG defect-induced tumorigenesis. Among these, four TE and three TS miRNAs have human homologs. From this study, we also identified 29 miRNAs that individually had no obvious role in enhancing or alleviating tumorigenesis despite their changed expression levels in nTSG tumors. This systematic analysis, which includes both RNA-Seq and in vivo functional studies, helps to categorize miRNAs into different groups based on their expression profile and functional relevance in epithelial tumorigenesis, whereas the evolutionarily conserved TE and TS miRNAs provide potential therapeutic targets for epithelial tumor treatment.
- ArticleGrodin EN, Burnette EM, Green R, Lim AC, Miotto K, Ray LA.Drug Alcohol Depend. 2021 08 01;225:108825.BACKGROUND: There is a strong bidirectional relationship between the use of alcohol and cigarettes which results in various challenges for treating those who co-use both substances. While varenicline and naltrexone each have FDA-approval for nicotine and alcohol use disorder, respectively, there is evidence that their clinical benefit may extend across the two disorders. Critically, the effect of combined varenicline and naltrexone on neural reactivity to alcohol cues among heavy drinking smokers has not yet been studied. Probing the effect of the combination therapy on alcohol cue-reactivity may give insight to the mechanisms underlying its efficacy.
METHODS: Forty-seven heavy drinking smokers enrolled in two medication studies were randomized to receive varenicline alone (n = 11), varenicline plus naltrexone (n = 11), or placebo (n = 25). Participants completed an fMRI alcohol cue-reactivity task and rated their in-scanner alcohol craving. Whole-brain analyses examined the effect of medication on alcohol cue-elicited neural response.
RESULTS: Varenicline plus naltrexone attenuated alcohol cue-elicited activation in mesolimbic regions relative to varenicline alone and to placebo (Z > 2.3, p < 0.05). The combination varenicline and naltrexone group also endorsed lower in-scanner alcohol craving relative to varenicline alone group (p = 0.04).
CONCLUSIONS: These findings provide evidence for the benefit of combined therapy of varenicline and naltrexone over varenicline alone for the attenuation of alcohol cue-elicited neural activation. This study provides a preliminary proof-of-mechanism for this combination pharmacotherapy and suggests that naltrexone may be driving the reductions in cue-elicited alcohol craving in the brain. Further clinical studies using the combined therapy to treat heavy drinking smokers are warranted. - ArticleWeigel M, Haas T, Wendebourg MJ, Schlaeger R, Bieri O.J Neurosci Methods. 2020 09 01;343:108825.BACKGROUND: Spinal cord (SC) gray and white matter atrophy quantification by advanced morphometric MRI can help to better characterize the course of neurodegenerative diseases in vivo, such as e.g. lower motor neuron disorders. Imaging the lower thoracic cord - containing those motor neurons that control leg function - could be particularly informative, however, is challenging due to tissue composition, physiological motion and large field of views.
NEW METHOD: An "averaged magnetization inversion recovery acquisitions" (AMIRA) approach with a radial k-space acquisition scheme was developed. The method is designed for morphometric SC imaging with a focus on the thoracic SC.
RESULTS: In a typical setting, radial AMIRA acquires transverse slices with a high 0.50 × 0.50mm2 in-plane resolution and a pronounced positive contrast between thoracic gray and white matter, within typically 2:39 min. Additional proof-of-concept measurements in patients demonstrate that such contrast and resolving capability is indeed necessary to assess potential atrophy of the anterior horns.
COMPARISON WITH EXISTING METHOD(S): Radial AMIRA utilizes two benefits of radial MRI techniques: being generally less prone to motion effects and that fold over artifacts can manifest less intrusively. These benefits are united with the original AMIRA approach which allows the contrast to be 'tuned' and improved based on the combination of five simultaneously acquired images of different tissue contrast.
CONCLUSIONS: Radial AMIRA is a promising approach for in vivo SC gray and white matter atrophy visualization and quantification in lower motor neuron diseases and other autoimmune or genetic diseases involving the entire (not only cervical) spinal cord. - ArticleMaverakis E, Merleev AA, Park D, Kailemia MJ, Xu G, Ruhaak LR, Kim K, Hong Q, Li Q, Leung P, Liakos W, Wan YY, Bowlus CL, Marusina AI, Lal NN, Xie Y, Luxardi G, Lebrilla CB.Clin Immunol. 2021 09;230:108825.We have recently introduced multiple reaction monitoring (MRM) mass spectrometry as a novel tool for glycan biomarker research and discovery. Herein, we employ this technique to characterize the site-specific glycan alterations associated with primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Glycopeptides associated with disease severity were also identified. Multinomial regression modelling was employed to construct and validate multi-analyte diagnostic models capable of accurately distinguishing PBC, PSC, and healthy controls from one another (AUC = 0.93 ± 0.03). Finally, to investigate how disease-relevant environmental factors can influence glycosylation, we characterized the ability of bile acids known to be differentially expressed in PBC to alter glycosylation. We hypothesize that this could be a mechanism by which altered self-antigens are generated and become targets for immune attack. This work demonstrates the utility of the MRM method to identify diagnostic site-specific glycan classifiers capable of distinguishing even related autoimmune diseases from one another.
- ArticleSchwebel FJ, Emery NN, Pfund RA, Pearson MR, Witkiewitz K.J Subst Abuse Treat. 2022 09;140:108825.INTRODUCTION: The goals of individuals seeking treatment for alcohol use disorder (AUD) are typically quantified as abstinent or nonabstinent (e.g., moderate drinking) goals. However, treatment goals can vary over time and be influenced by life circumstances. This study aims to identify predictors of treatment goal change and direction of change from baseline to six-month follow-up among individuals seeking treatment for AUD.
METHODS: This study is a secondary analysis of data from the Relapse Replication and Extension Project. The study included participants who completed assessments at baseline and six-month follow-up in the analysis (n = 441). We used decision trees to examine 111 potential predictors of treatment goal change. The study cross-validated results using random forests. The team examined changes in goal between baseline and follow-up (Decision Tree 1) and quantified them as being toward or away from a complete abstinence goal (Decision Tree 2).
RESULTS: Nearly 50 % of the sample changed their treatment goal from baseline to 6 months, and 68.7 % changed from a nonabstinence goal toward a complete abstinence goal. The study identified seven unique predictors of goal change. The most common predictors of changing a treatment goal were number of recent treatment sessions prior to enrolling in the study, other substance use, negative affect, anxiety, social support, and baseline drinks per drinking day. Participants with a greater number of recent treatment sessions and who sought social support were most likely to change their goal. Additionally, individuals with more substance use tended to change away from complete abstinence goals. Cross-validation supported baseline drinks per drinking day, social support, baseline maximum blood alcohol concentration (BAC), lifetime tobacco use, baseline average BAC, lifetime cocaine use, Inventory of Drinking Situations total score, and Situational Confidence Questionnaire average score as important predictors.
CONCLUSIONS: This study identified seven unique predictors of treatment goal change while in AUD treatment. Prior treatment, drinking to cope, and social support were most associated with goal changes. This information can inform providers who seek to understand factors associated with treatment goal selection and changes in goals during treatment. - ArticleCromer SJ, Wexler DJ, Kazemian P.Diabetes Res Clin Pract. 2021 May;175:108825.BACKGROUND: Given the shift from use of less expensive human to costlier analog insulins for treatment of type 2 diabetes (T2D), we examine characteristics and glycemic control associated with type of basal insulin use.
METHODS: We analyzed respondents with T2D in six consecutive National Health and Nutrition Examination Survey (NHANES) cycles (2005-2016). Logistic regression models examined associations between demographics, socioeconomic factors, and NHANES cycle with (1) type of basal insulin use and (2) hemoglobin A1c <8.0% and <7.0% according to basal insulin type.
FINDINGS: Basal insulin use increased from 9.6% to 17.2% of respondents with T2D between 2005 and 2016. Among 723 respondents meeting inclusion criteria, the proportion using analog basal insulin rose from 58% to 88%. African American (aOR 0.42, 95% CI 0.24-0.74) and Hispanic (aOR 0.54, 95% CI 0.30-0.96) respondents had lower odds of analog basal insulin use than non-Hispanic White respondents in adjusted and unadjusted models. Older age and having health insurance, but not type of basal insulin use, associated with meeting HbA1c targets.
INTERPRETATION: Non-White NHANES respondents were less likely to use analog basal insulin than White respondents. Increased analog basal insulin use between 2005 and 2016 was not associated with improved glycemic control. - ArticleFu J, Fang MJ, Dong D, Li J, Sun YS, Tian J, Tang L.Eur J Radiol. 2020 Apr;125:108825.PURPOSE: To determine if texture features of diffusion weighted imaging (DWI) on MRI of metastatic gastrointestinal stromal tumor (mGIST) have correlation with overall survival (OS).
METHOD: Fifty-one GIST patients with metastatic lesions who received imatinib targeted therapy were included. Texture features of the largest metastatic lesion were analyzed using inhouse software. Three types of texture features were assessed: fractal features, gray-level co-occurrence matrix (GLCM) features, and gray-level run-length matrix (GLRLM) features. The features were extracted from the regions of interest (ROIs) on T2-weighted imaging (T2WI), DWI and apparent diffusion coefficient (ADC) maps. Histogram analysis was performed on ADC maps. Patients were followed up until death. Kaplan-Meier analysis was performed to determine the correlation of texture features with OS. The curves of the high- and low-risk groups were compared using log-rank test. The prognostic efficacy of the predictors was assessed by calculating the concordance probability.
RESULTS: The median survival time was 43.5 months (range, 3.97-120.90 m). Four DWI and three ADC texture features showed significant correlation with OS on univariate analysis (p < 0.05). DWI_L_GLCM_maximum_probability [hazard ratio (HR): 2.062 (1.357-3.131)], ADC_H_GLRLM_mean [HR: 2.174 (1.457-3.244)], and ADC_O_GLCM_cluster_shade [HR: 1.882 (1.324-2.674)] were identified as representative prognostic indicators. The optimum threshold levels for these three features were 1.19×100, 1.71×10 and 2.19×0.1, respectively. Neither histogram analysis values nor fractal features revealed significant correlation with survival status (p > 0.05).
CONCLUSIONS: Texture features of the mGIST on DWI exhibited correlation with overall survival. High-grade heterogeneity was associated with poor prognosis. - ArticleZhang L, Li S, Wang R, Chen C, Ma W, Cai H.Biomed Pharmacother. 2019 Jun;114:108825.Large tumor suppressor 2 (LATS2), an important mediator of the cell apoptotic response pathway, has been linked to the progression of several cancers. Here, we described the molecular feature of LATS2 as a novel antitumor factor in liver cancer cells in vitro. Western blotting was used to detect the expression of LATS2 and its downstream factors. ELISA, immunofluorescence, and flow cytometry were used to evaluate the alterations of mitochondrial function in response to LATS2 overexpression. Adenovirus-loaded LATS2 and siRNA against DRP1 were transfected into liver cancer cells to overexpress LATS2 and knockdown DRP1 expression, respectively. The results of the present study demonstrated that overexpression of LATS2 was closely associated with more liver cancer cell death. Mechanistically, LATS2 overexpression increased the expression of DRP1, and DRP1 elevated mitochondrial division, an effect that was accompanied by mitochondrial dysfunction, including mitochondrial membrane potential reduction, mitochondrial respiratory complex downregulation, mitochondrial cyt-c release into the nucleus and mitochondrial oxidative injury. Moreover, LATS2 overexpression also initiated mitochondrial apoptosis, and this process was highly dependent on DRP1-related mitochondrial division. Molecular investigations demonstrated that LATS2 modulated DRP1 expression via the Wnt/β-catenin pathway. Inhibition of the Wnt/β-catenin pathway pregented LATS2-mediated DRP1 upregulation, ultimately sustaining mitochondrial function and cell viability in the presence of LATS2 overexpression. Altogether, the above data identify LATS2-Wnt/β-catenin/DRP1/mitochondrial division as a novel anticancer signaling pathway promoting cancer cell death, which might be an attractive therapeutic target for the treatment of hepatocellular carcinoma.