Storage, Disposal, and Use of Opioids Among Cancer Patients in Central China: A Multi-Center Cross-Sectional Study.

OBJECTIVE: Unsafe opioid-related practices can lead to abuse, diversion, and accidental overdoses. In this study, we aimed to describe the patterns and beliefs regarding the storage, disposal, and use of opioids among Chinese patients with cancer in their home settings, which remain unclear. METHODS: A multicenter cross-sectional survey was conducted in Hubei Province from October 2022 to June 2023. We collected information on the storage, disposal, and use of opioids among cancer pain inpatients in the oncology department. Logistic regression was used to estimate the factors associated with unsafe disposal and use of opioids. RESULTS: The survey included 221 patients with a median age of 62 years. Only 3.2% stored their opioids under lock and key, and 49.8% were unaware of proper disposal methods. Nearly one-fifth (19.5%) reported having received information on the safe storage (14.0%) and/or disposal (10.0%) of opioids. A total of 44.3% reported unsafe use by sharing (1.8%), losing (4.1%), or taking opioids at a higher dose than prescribed (42.5%). Patients who did not receive information on the safe disposal of opioids (OR = 4.57, P = .0423), had a history of alcohol use (OR = 1.91, P = .0399), and used opioids other than morphine (OR = 2.31, P = .0461) had higher odds of unsafe disposal practices. Individuals with an associate degree/bachelor's degree or above were less likely to dispose of (OR = 0.36, P = .0261) and use (OR = 0.31, P = .0127) opioids unsafely. CONCLUSION: A significant proportion of Chinese patients with cancer exhibit unsafe practices in the storage, disposal, and use of opioids. The study highlights an urgent need for implementing routine education programs and drug "take-back" initiatives to improve opioid-related practices.

Meta Analysis of the Effects of Thalassemia Minor on the Incidence of Amniotic Fluid Abnormalities and the Amount of Bleeding During Delivery.

Objective: To analyze the effects of thalassemia minor on the incidence of amniotic fluid abnormalities and the blood loss of pregnant women during delivery based on the database. Methods: PubMed, EMBASE, EBSCO, Web of Knowledge and Ovid databases were searched for articles on the incidence of amniotic fluid abnormalities and the amount of bleeding during delivery in pregnant women with mild thalassemia; it can also be combined with manual retrieval for literature review. The data retrieval period was from the establishment of the database to June 2022. According to the Newcastle Ottawa scale score, the quality of the six included literature was evaluated, and the Revman processing software was used for meta-analysis. Results: The 6 included articles are all high-quality literature, including 364 cases in the case group and 689 cases in the control group. The publication years of the literature are mainly from 2013 to 2021, and they are all high-quality literature. All literature was blinded, and a total of 4 pregnancy outcomes were extracted from the 6 included literature, including oligohydramnios/oligohydramnios, postpartum hemorrhage, preterm delivery, and cesarean section. Compared to normal pregnant women, the level of postpartum bleeding in thalassemia pregnant women was significantly increased [RR = 2.40, 95% CI (1.63-3.54), P < .05], and the difference was statistically significant. Compared to normal pregnant women, thalassemia pregnant women have a significantly higher risk of developing excessive/insufficient amniotic fluid [RR = 2.71, 95% CI (2.52-2.81), P < .01], and the difference is statistically significant. Compared to normal pregnant women, pregnant women with thalassemia have a significantly higher risk of premature birth [RR = 3.02, 95% CI (1.84~4.96), P < .05], and the difference is statistically significant. Compared to normal pregnant women, the risk of cesarean section in thalassemia pregnant women is significantly increased [RR = 1.68, 95% CI (1.39-2.02), P < .05], and the difference is statistically significant. Conclusion: Thalassemia minor can increase the incidence of amniotic fluid abnormalities and the amount of bleeding during labor. In the future, we should strengthen the health education of pregnant women, improve the understanding of the disease, avoid or reduce the impact of thalassemia on newborns, improve the pregnancy outcome, and provide a more reliable basis for clinical decision-making.However, there are still certain limitations: (1) the literature selected in the study for the past 5 years is relatively small, and they are all single center, retrospective studies, and have a small sample size, resulting in insufficient accuracy of the results of the meta-analysis; (2) Some literature lacks blind methods, which may lead to language bias and implementation bias in the results; (3) The research time is still short, and it has not been clear how different types of thalassemia affect abnormal amniotic fluid volume and postpartum bleeding.

Mechanistic Study of Icaritin-Induced Inactivation of Cytochrome P450 2C9.

Icaritin (ICT) is a prenylflavonoid derivative that has been approved by National Medical Products Administration for the treatment of hepatocellular carcinoma. This study aims to evaluate the potential inhibitory effect of ICT against cytochrome P450 (CYP) enzymes and to elucidate the inactivation mechanisms. Results showed that ICT inactivated CYP2C9 in a time-, concentration-, and NADPH-dependent manner with Ki = 1.896 µM, Kinact = 0.02298 minutes-1, and Kinact/Ki = 12 minutes-1 mM-1, whereas the activities of other CYP isozymes was minimally affected. Additionally, the presence of CYP2C9 competitive inhibitor, sulfaphenazole, superoxide dismutase/catalase system, and GSH all protected CYP2C9 from ICT-induced activity loss. Moreover, the activity loss was neither recovered by washing the ICT-CYP2C9 preincubation mixture nor the addition of potassium ferricyanide. These results, collectively, implied the underlying inactivation mechanism involved the covalent binding of ICT to the apoprotein and/or the prosthetic heme of CYP2C9. Furthermore, an ICT-quinone methide (QM)-derived GSH adduct was identified, and human glutathione S-transferases (GST) isozymes GSTA1-1, GSTM1-1, and GSTP1-1 were shown to be substantially involved in the detoxification of ICT-QM. Interestingly, our systematic molecular modeling work predicted that ICT-QM was covalently bound to C216, a cysteine residue located in the F-G loop downstream of substrate recognition site (SRS) 2 in CYP2C9. The sequential molecular dynamics simulation confirmed the binding to C216 induced a conformational change in the active catalytic center of CYP2C9. Lastly, the potential risks of clinical drug-drug interactions triggered by ICT as a perpetrator were extrapolated. In summary, this work confirmed that ICT was an inactivator of CYP2C9. SIGNIFICANCE STATEMENT: This study is the first to report the time-dependent inhibition of CYP2C9 by icaritin (ICT) and the intrinsic molecular mechanism behind it. Experimental data indicated that the inactivation was via irreversible covalent binding of ICT-quinone methide to CYP2C9, while molecular modeling analysis provided additional evidence by predicting C216 as the key binding site which influenced the structural confirmation of CYP2C9's catalytic center. These findings suggest the potential of drug-drug interactions when ICT is co-administered with CYP2C9 substrates clinically.

Identification of novel tumor-associated antigens and evaluation of a panel of autoantibodies in detecting oral cancer.

BACKGROUND: We aimed to identify tumor-associated antigen (TAA) biomarkers through bioinformatic analysis and experimental verification, and to evaluate a panel of autoantibodies against tumor-associated antigens (TAAbs) for the detection of oral cancer (OC). METHODS: GEO and TCGA databases were used to screen significantly up-regulated genes related to OC, and protein-protein interaction (PPI) analysis and Cystoscope software were used to identify key genes. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of autoantibodies in 173 OC patients and 173 normal controls, and binary logistic regression analysis was used to build a diagnostic model. RESULTS: Using bioinformatics, we identified 10 key genes (AURKA, AURKB, CXCL8, CXCL10, COL1A1, FN1, FOXM1, MMP9, SPP1 and UBE2C) that were highly expressed in OC. Three autoantibodies (anti-AURKA, anti-CXCL10, anti-FOXM1) were proven to have diagnostic value for OC in the verification set and the validation set. The combined assessment of these three autoantibodies improved the diagnostic value for OC, with an area under the curve (AUC), sensitivity and specificity of 0.741(95%CI:0.690-0.793),58.4% and 80.4%, respectively. In addition, the combination of these three autoantibodies also had high diagnostic value for oral squamous cell carcinoma (OSCC), with an AUC, sensitivity and specificity of 0.731(95%CI:0.674,0.786), 53.8% and 82.1%, respectively. CONCLUSIONS: Our study revealed that AURKA, CXCL10 and FOXM1 may be potential biomarkers and the panel of three autoantibodies (anti-AURKA, anti-CXCL10 and anti-FOXM1) had good diagnostic value for OC.

Ubiquitin E3 ligase AtCHYR2 functions in glucose regulation of germination and post-germinative growth in Arabidopsis thaliana.

KEY MESSAGE: Cytoplasm-localized RING ubiquitin E3 ligase AtCHYR2 involved in plant glucose responses during germination and post-germinative growth. CHY ZINC FINGER AND RING PROTEIN (CHYR) containing both a CHY zinc finger and a C3H2C3-type RING domain plays important roles in plant drought tolerance and the abscisic acid (ABA) response; however, their functions in sugar signaling pathways are less studied. Here, we report a glucose (Glc) response gene AtCHYR2, a homolog of RZFP34/CHYR1, which is induced by various abiotic stresses, ABA, and sugar treatments. In vitro, we demonstrated that AtCHYR2 is a cytoplasm-localized RING ubiquitin E3 ligase. Overexpression of AtCHYR2 led to hypersensitivity to Glc and enhanced Glc-mediated inhibition of cotyledon greening and post-germinative growth. Contrastingly, AtCHYR2 loss-of-function plants were insensitive to Glc-regulated seed germination and primary root growth, suggesting that AtCHYR2 is a positively regulator of the plant glucose response. Additionally, physiological analyses showed that overexpression AtCHYR2 increased stomata aperture and photosynthesis under normal condition, and promoted accumulation of endogenous soluble sugar and starch in response to high Glc. Genome-wide RNA sequencing analysis showed that AtCHYR2 affects a major proportion of Glc-responsive genes. Particularly, sugar marker gene expression analysis suggested that AtCHYR2 enhances the Glc response via a signaling pathway dependent on glucose metabolism. Taken together, our findings show that a novel RING ubiquitin E3 ligase, AtCHYR2, plays an important role in glucose responses in Arabidopsis.

Subacute oral toxicology and toxicokinetics of pterostilbene, a novel Top1/Tdp1 inhibiting anti-tumor reagent.

This study evaluated the subacute toxicity and toxicokinetics of a potential anti-cancer drug candidate, pterostilbene, in rats. Animals were orally administered at two repeated doses of 200 and 500 mg/kg for 28 days. No mortality was observed during the 28 days of continuous administration of pterostilbene. Body weight and food consumption in each group increased steadily, while no significant difference was found. Liver weight in the 500 mg/kg female, but not male group increased with mild cytoplasmic vacuoles observed in histopathological study. Toxicokinetics was assessed by measuring plasma concentrations of pterostilbene on the first and 28th day of administration using UPLC-MS/MS. Toxicokinetic parameters showed that AUC0-t significantly increased in all animals, while the increase in females was greater than males. System exposure of pterostilbene appeared to be linear within the administrated dose range. In conclusion, our findings suggested a minimal subacute toxicity profile of pterostilbene, which could strongly support further development of this compound as a novel anti-cancer agent.

ROS-Targeted Depression Therapy via BSA-Incubated Ceria Nanoclusters.

Depression is one of the most fatal mental diseases, and there is currently a lack of efficient drugs for the treatment of depression. Emerging evidence has indicated oxidative stress as a key pathological feature of depression. We targeted reactive oxygen species (ROS) and synthesized CeO2@BSA nanoclusters as a novel antidepression nanodrug via a convenient, green, and highly effective bovine serum albumin (BSA) incubation strategy. CeO2@BSA has ultrasmall size (2 nm) with outstanding ROS scavenging and blood-brain barrier crossing capacity, rapid metabolism, and negligible adverse effects in vitro and in vivo. CeO2@BSA administration alleviates depressive behaviors and depression-related pathological changes of the chronic restraint stress-induced depressive model, suggesting promising therapeutic effects of CeO2@BSA for the treatment of depression. Our study proved the validity by directly using nanodrugs as antidepression drugs instead of using them as a nanocarrier, which greatly expands the application of nanomaterials in depression treatment.

The Typical Polybrominated Diphenyl Ethers (PBDEs) and Heavy Metals Distributions in a Formal e-Waste Dismantling Site.

Understanding the release of pollutants from the formal e-waste dismantling site could provide the basic information and potential risk to guide the normative regulation of the process. In this study, the distribution of typical polybrominated diphenyl ethers (PBDEs) and heavy metals in a relocating site of a formal e-waste dismantling company was firstly investigated down to the saturated zone, with a maximum depth of 3.0 m. The mean concentrations of Σ13PBDEs were ranged from 2.815 to 7.178 ng/g, with a peak value of 7.178 ng/g in storage area. BDE-209 was the predominant congener of PBDEs in the soil, with the value ranged from 1.688 to 2.483 ng/g. A higher pollution of PBDEs and HMs was presented in the storage area. The risk assessment of PBDEs mostly posed a low environmental risk (RQ ≤ 0.01) and pentaBDE was found to be the most harmful driver for the potential environmental risk.

VisProDom: an interactive Shiny/R application for displaying protein domains with transcriptional features.

BACKGROUND: Both the protein domains and transcript structures influence protein functional variation. The genomic location of both protein domains and transcript structural features can be described using the genomic coordinates of their encoded sequences. However, the coordinates of protein domains and transcriptional features often differ greatly, and it is difficult to view them in combination at the genome-wide level. In this paper, we describe the development of a new tool that allows users to visualize domains and transcript features together, using either built-in or uploaded genome datasets, and export publication-ready figures.  RESULTS: We developed a user-friendly, independent R package and Shiny web application named "VisProDom". VisProDom consists of a genome-wide database containing entire annotated transcripts merged with annotated protein domains from the Pfam database. The built-in dataset includes 82 files, which merge genome general feature format (GFF) annotations with rpsblast tabular outputs from protein sequence searches in the Pfam database. Multiple genomes can be simultaneously screened for protein domains or transcript names. VisProDom includes step-by-step introductions and clickable elements for ease of use. CONCLUSION: VisProDom can display hundreds of transcripts alongside protein domains and export figures in a publication-ready format. This makes it a valuable tool for molecular evolution and comparative genomics.

Absence of TNF Leads to Alternative Activation in Peritoneal Macrophages in Experimental Listeria Monocytogenes Infection.

Macrophages are crucial effectors of innate immunity against the pathogenic bacterium Listeria monocytogenes. The pro-inflammatory cytokine tumour necrosis factor-α (TNF) has been shown to be crucial for resistance to L. monocytogenes and mice deficient in TNF signalling succumb quickly after infection. However, the mechanisms underlying TNF-mediated defence against L. monocytogenes infection have not been completely elucidated. Here, we demonstrate that TNF concurrently functions to support a pro-inflammatory M1 phenotype while actively blocking macrophage polarization to the M2 phenotype. Compared to WT mice, peritoneal macrophages in TNF-deficient mice inoculated with L. monocytogenes respond with M2 polarization by upregulating Arg1. Consistently, TNF blockade in vitro resulted in M2 polarization in peritoneal macrophages during L. monocytogenes infection. Additionally, TNF promotes the transition from M2 to M1 polarization in peritoneal macrophages. Further investigation of peritoneal macrophage polarization suggested the NF-κB pathway is involved in the TNF-dependent M2 to M1 shift. Conversely, treatment of peritoneal macrophage with a PPARγ agonist blunted the expression of M1 genes induced by TNF and reduced NF-κB signalling pathway activation. Competing signalling mechanisms therefore play an essential role in the ability of peritoneal macrophage to resolve L. monocytogenes infections with TNF playing an essential role in driving M1 polarization.Abbreviations: LPM: large peritoneal macrophage; SPM: small peritoneal macrophage; LLO: listeriolysin O; iNOS: inducible nitric oxide synthase; DCs: dendritic cells.

Insulin-incubated palladium clusters promote recovery after brain injury.

Traumatic brain injury (TBI) is a cause of disability and death worldwide, but there are currently no specific treatments for this condition. Release of excess reactive oxygen species (ROS) in the injured brain leads to a series of pathological changes; thus, eliminating ROS could be a potential therapeutic strategy. Herein, we synthesized insulin-incubated ultrasmall palladium (Pd@insulin) clusters via green biomimetic chemistry. The Pd@insulin clusters, which were 3.2 nm in diameter, exhibited marked multiple ROS-scavenging ability testified by the theoretical calculation. Pd@insulin could be rapidly excreted via kidney-urine metabolism and induce negligible adverse effects after a long-time treatment in vivo. In a TBI mouse model, intravenously injected Pd@insulin clusters aggregated in the injured cortex, effectively suppressed excessive ROS production, and significantly rescued motor function, cognition and spatial memory. We found that the positive therapeutic effects of the Pd@insulin clusters were mainly attributed to their ROS-scavenging ability, as they inhibited excessive neuroinflammation, reduced cell apoptosis, and prevented neuronal loss. Therefore, the ability of Pd@insulin clusters to effectively eliminate ROS, as well as their simple structure, easy synthesis, low toxicity, and rapid metabolism may facilitate their clinical translation for TBI treatment.

Adult-onset vanishing white matter in a patient with EIF2B3 variants misdiagnosed as multiple sclerosis.

BACKGROUND: Vanishing white matter (VWM) is an autosomal recessive disorder characterized by childhood ataxia with central hypomyelination. Adult-onset VWM should be considered as a differential diagnosis for suspected cases of multiple sclerosis (MS). METHODS: Targeted region sequencing (TRS) and Sanger sequencing validation were performed to identify and validate the likely pathogenic mutations in a family with VWM. RESULTS: The main clinical manifestations of the proband included decreased vision and sleepiness accompanied by atrophy of the corpus callosum, affected inner rim of the corpus callosum, decreased apparent diffusion coefficient value or persistent hyperintensity-diffusion-weighted imaging, atrophied optic nerve, and no recordable visual evoked potentials. Due to the slow development and atypical VWM image features, MS was initially suspected. After prednisone was administered, the patient's condition did not improve significantly, and other diseases were considered. The TRS and Sanger sequencing identified compound heterozygous mutations of EIF2B3 in the proband; c.965C > G /p.Ala322Gly in exon 8 and c.130G > A/p.Glu44Lys in exon 2 were missense mutations inherited from the mother and father, respectively. The proband's oldest brother had the same compound heterozygous mutations but showed no symptoms. CONCLUSION: This is the first report of adult-onset VWM in a Chinese family. Initially, MS was suspected, and genetic testing confirmed the diagnosis of VWM. This study may further broaden the clinical spectrum of EIF2B3, thus providing a foundation for further research on the pathogenesis and genetic therapy for VWM.

Metabolites identification and species comparison of Oroxylin A, an anti-cancer flavonoid, in vitro and in vivo by HPLC-Q-TOF-MS/MS.

Oroxylin A, the main component of Scutellaria baicalensis Georigi has been widely studied due to its well-known pharmacological effects. According to previous studies, Oroxylin A with low bioavailability was converted into glucuronidation and sulphonated metabolites, which had high exposure in plasma and generated certain activities. It is necessary to study the metabolites and metabolic pathways of Oroxylin A.This study aimed to explore the metabolites of Oroxylin A in liver microsomes, primary hepatocyte incubation samples of five different species (human, monkey, dog, mouse, rat), and in bile, urine and faeces of rats.It would provide a systematic description of metabolic pathway of Oroxylin A. Also, a method of high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry detector (HPLC-Q-TOF-MS/MS) for identification of each metabolite in various biological matrices was developed.This experiment illustrated that phase II metabolites were the main form of Oroxylin A in vitro and in excretion of rats, accompanied with a small amount of phase I metabolites.Furthermore, there were obvious species differences among the metabolism in vitro, especially in phase II. Monkeys and rats may be more suitable for preclinical research than dogs and mice as non-rodent or rodent species.

Analysis on advances and characteristics of microplastic pollution in China's lake ecosystems.

China is the largest producer and consumer of plastics worldwide. Microplastic (MP) pollution has been a recent research hotspot in environmental science and ecology. This study collects and analyzes the statistical data for microplastics (MPs) 86 lakes in entire China's lake ecosystems in past five years (2016-2020), their range in area is 0.056-4543.000 km2 (average: 566.045 km2), and the water storage varies from 0.162 × 108 to 1050.000 × 108 m3 (average: 77.884 ×108 m3). The results showed (1) The MP abundance in lake surface water is significantly correlated with lake area (ρ = -0.562, p ＜0.01), provincial GDP (Gross Domestic Product, GDP) (ρ = 0.377, p = 0.002), GDP per capita (ρ = 0.346, p = 0.006), urban waste water discharge and ratio of agricultural land area (ρ = 0.369, p = 0.003). (2) The MP abundance in lake sediment is significantly correlated with per capita domestic volume of garbage disposal (ρ = -0.536, p ＜0.001), per capita urban waste water discharge (ρ = -0.544, p ＜0.001) and ratio of agricultural land area (ρ = 0.635, p ＜0.001). (3) Irrespective of whether the samples were from surface water or sediment, MPs were primarily transparent, and the dominant types were fragments, films, and fibers. In addition, the size of MPs samples was mostly less than 2 mm, and the major polymers were polyethylene (PE), polypropylene (PP), and polystyrene (PS). (4) The degree of MP pollution in organisms was related to the degree of environmental pollution. These findings could provide a theoretical basis for the control and management of MP pollution in China's lake ecosystems.

Anti-CXCL8 Autoantibody: A Potential Diagnostic Biomarker for Esophageal Squamous Cell Carcinoma.

Background and Objectives: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies. Anti-tumor associated antigen autoantibodies (TAAbs) can be used as biomarkers for tumor detection. The aim of this study was to identify a reliable TAAb as the diagnostic marker for ESCC. Materials and Methods: The Cancer Genome Atlas (TCGA) database was used to screen candidate genes. The mRNA expression of the key gene was then verified by micro array dataset GSE44021 from the Gene Expression Omnibus (GEO) database and the diag nostic value of the corresponding autoantibody to the key gene in ESCC was detected by enzyme-linked im muno sorbent assay (ELISA). Results: CXCL8 was identified as the key gene. The dataset GSE44021 showed that CXCL8 mRNA expression was prominently over-expressed in ESCC tissues compared with normal tissues. ELISA results showed that the level of anti-CXCL8 autoantibody in ESCC patients was significantly higher than in normal controls and the receiver operating char ac teristic (ROC) curve indicated that anti-CXCL8 autoantibody could discriminate ESCC patients from normal controls, with the area under the ROC curve (AUC) for the verification cohort, and the validation cohort were 0.713 and 0.751, respectively. Conclusions: Our study illustrated that anti-CXCL8 autoantibody had good diagnostic value, and may become a candidate biomarker for ESCC.

Determination of oroxylin A, oroxylin A 7-O-glucuronide, and oroxylin A sodium sulfonate in beagle dogs by using UHPLC MS/MS Application in a pharmacokinetic study.

Oroxylin A, obtained from the root of Scutellaria baicalensis Georgi, is a flavonoid with antitumor and other pharmacological activities. Our previous studies showed for the first time that it is mainly metabolized to oroxylin A sodium sulfonate by sulfotransferase enzymes in beagle dogs. In this study, rapid, universal, selective, and robust ultra-high-performance liquid chromatography-tandem mass spectrometry methods were established and fully validated to quantitatively detect oroxylin A, oroxylin A 7-O-glucuronide, and oroxylin A sodium sulfonate in beagle dog plasma. The quantitative analysis for oroxylin A sodium sulfonate was reported for the first time. Plasma samples were processed with acetonitrile, a universal protein precipitant. Gradient elution was performed to resolve carryover effects and to achieve separation efficiency and sufficient chromatographic retention. The linear relationships of oroxylin A, oroxylin A 7-O-glucuronide, and oroxylin A sodium sulfonate in plasma were in the range of 2.0-500.0, 5.0-500.0, and 1.881-940.5 ng/mL, respectively. The assay method was successfully applied to pharmacokinetic study. This is the first paper that reveals the pharmacokinetic profile of oroxylin A, oroxylin A 7-O-glucuronide, and oroxylin A sodium sulfonate after single-dose intravenous and oral administration of Oroxylin A in beagle dogs.

MicroRNA-4461 derived from bone marrow mesenchymal stem cell exosomes inhibits tumorigenesis by downregulating COPB2 expression in colorectal cancer.

Colorectal cancer (CRC) is one of the main cause of cancer-related deaths. It's reported that bone marrow mesenchymal stem cells (BMSCs) affects tumor development through secreting exosomes. This study aims to investigate the function of BMSCs-derived exosome miR-4461 in CRC. The results of qRT-PCR showed that miR-4461 expression in DLD1, HCT116 and SW480 CRC cells and CRC tissues was lower than that in FHC cells and normal tissues, respectively. And COPB2 mRNA expression was negatively correlated with miR-4461. Western blot was used to detect COPB2 protein expression. Dual-luciferase reporter assay results revealed that miR-4461 targeted COPB2. Transwell assay and CCK-8 assay demonstrated that COPB2 knockdown inhibited HCT116 and SW480 cells proliferation, migration and invasion abilities. Furthermore, BMSCs-derived exosome miR-4461 downregulated COPB2 expression and inhibited HCT116 and SW480 cells migration and invasion. The findings demonstrated that miR-4461 could be a potential target for the diagnosis and treatment of colorectal cancer.

Determination of Serum Homocysteine and Hypersensitive C-reactive Protein and Their Correlation with Premature Coronary Heart Disease.

BACKGROUND: This study aims to investigate the correlation between premature coronary heart disease (pCHD) and both serum homocysteine (Hcy) and hypersensitive C-reactive protein (hs-CRP). METHODS: A total of 170 patients with pCHD were enrolled in this study from June 2014 to April 2016 (including 52 patients with stable angina pectoris [SAP], 70 patients with unstable angina pectoris [UAP], and 48 patients with acute myocardial infarction [AMI]), together with 105 healthy controls (CON) selected at the same period, to observe the changes of Hcy and hs-CRP in CHD patients and those with different types of CHD. RESULTS: The levels of serum Hcy and hs-CRP in group pCHD were significantly higher than in group CON (P < .05). The levels of Hcy and hs-CRP in group AMI were significantly higher than in group UAP and group SAP (P < .05). The changes of serum Hcy and hs-CRP were significantly higher in patients with multi-vascular lesions and dual-vascular lesions than in those with single-vascular lesion (P < .05). CONCLUSION: The levels of serum Hcy and hs-CRP in CHD patients are positively correlated with the severity of CHD, which increase with the increase of lesion count. The combined detection of Hcy and hs-CRP can initially reflect the severity of coronary artery, thus better guiding treatment and predicting prognosis.

Relationship Between Polymorphism of Adiponectin Gene SNPS+276 and Coronary Heart Disease.

BACKGROUND: This study aims to investigate the relationship between polymorphism of adiponectin (ADIPOQ) gene SNPS+276 and the severity of coronary heart disease (CHD) and coronary artery disease (CAD). METHODS: A total of 582 inpatients were enrolled and divided into Group CHD (342 cases) and the control group (CON, 240 cases), according to their angiographic results from June 2014 to April 2016 for the genotype (G/T) analysis of ADIPOQ SNPs+276 by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Group CHD: GG 110 (32%), GT 205 (59%), and TT27 (8%); Group CON: GG 36 (15%), GT 161 (67%), and TT 43 (18%) (P < .05). The frequency of allele G in group CHD was 62.1% and 48.5% in group CON (P < .05). The frequencies of genotype GG, GT, and TT were 67 (33.3%), 107 (53.2%), and 27 (13.5%), respectively, in the group with single vascular lesion, and 64 (45.4%), 53 (37.6%), and 24 (17%), respectively, in the group with multiple vascular lesions. There was statistical significance between the two groups (P < .05). CONCLUSIONS: The 276G gene of adiponectin may be a susceptibility gene of CHD, and the genotype GG may be related to the severity of this disease.

TNF-α promotes extracellular vesicle release in mouse astrocytes through glutaminase.

BACKGROUND: Extracellular vesicles (EVs) are membrane-contained vesicles shed from cells. EVs contain proteins, lipids, and nucleotides, all of which play important roles in intercellular communication. The release of EVs is known to increase during neuroinflammation. Glutaminase, a mitochondrial enzyme that converts glutamine to glutamate, has been implicated in the biogenesis of EVs. We have previously demonstrated that TNF-α promotes glutaminase expression in neurons. However, the expression and the functionality of glutaminase in astrocytes during neuroinflammation remain unknown. We posit that TNF-α can promote the release of EVs in astrocytes through upregulation of glutaminase expression. RESULTS: Release of EVs, which was demonstrated by electron microscopy, nanoparticle tracking analysis (NTA), and Western Blot, increased in mouse astrocytes when treated with TNF-α. Furthermore, TNF-α treatment significantly upregulated protein levels of glutaminase and increased the production of glutamate, suggesting that glutaminase activity is increased after TNF-α treatment. Interestingly, pretreatment with a glutaminase inhibitor blocked TNF-α-mediated generation of reactive oxygen species in astrocytes, which indicates that glutaminase activity contributes to stress in astrocytes during neuroinflammation. TNF-α-mediated increased release of EVs can be blocked by either the glutaminase inhibitor, antioxidant N-acetyl-L-cysteine, or genetic knockout of glutaminase, suggesting that glutaminase plays an important role in astrocyte EV release during neuroinflammation. CONCLUSIONS: These findings suggest that glutaminase is an important metabolic factor controlling EV release from astrocytes during neuroinflammation.