Effect of Colchicine on Coronary Plaque Stability in Acute Coronary Syndrome as Assessed by Optical Coherence Tomography: The COLOCT Randomized Clinical Trial.

BACKGROUND: Colchicine has been approved to reduce cardiovascular risk in patients with coronary heart disease on the basis of its potential benefits demonstrated in the COLCOT (Colchicine-Optical Coherence Tomography Trial) and LoDoCo2 studies. Nevertheless, there are limited data available about the specific impact of colchicine on coronary plaques. METHODS: This was a prospective, single-center, randomized, double-blind clinical trial. From May 3, 2021, until August 31, 2022, a total of 128 patients with acute coronary syndrome aged 18 to 80 years with lipid-rich plaque (lipid pool arc >90°) detected by optical coherence tomography were included. The subjects were randomly assigned in a 1:1 ratio to receive either colchicine (0.5 mg once daily) or placebo for 12 months. The primary end point was the change in the minimal fibrous cap thickness from baseline to the 12-month follow-up. RESULTS: Among 128 patients, 52 in the colchicine group and 52 in the placebo group completed the study. The mean age of the 128 patients was 58.0±9.8 years, and 25.0% were female. Compared with placebo, colchicine therapy significantly increased the minimal fibrous cap thickness (51.9 [95% CI, 32.8 to 71.0] µm versus 87.2 [95% CI, 69.9 to 104.5] µm; difference, 34.2 [95% CI, 9.7 to 58.6] µm; P=0.006), and reduced average lipid arc (-25.2° [95% CI, -30.6° to -19.9°] versus -35.7° [95% CI, -40.5° to -30.8°]; difference, -10.5° [95% CI, -17.7° to -3.4°]; P=0.004), mean angular extension of macrophages (-8.9° [95% CI, -13.3° to -4.6°] versus -14.0° [95% CI, -18.0° to -10.0°]; difference, -6.0° [95% CI, -11.8° to -0.2°]; P=0.044), high-sensitivity C-reactive protein level (geometric mean ratio, 0.6 [95% CI, 0.4 to 1.0] versus 0.3 [95% CI, 0.2 to 0.5]; difference, 0.5 [95% CI, 0.3 to 1.0]; P=0.046), interleukin-6 level (geometric mean ratio, 0.8 [95% CI, 0.6 to 1.1] versus 0.5 [95% CI, 0.4 to 0.7]; difference, 0.6 [95% CI, 0.4 to 0.9]; P=0.025), and myeloperoxidase level (geometric mean ratio, 1.0 [95% CI, 0.8 to 1.2] versus 0.8 [95% CI, 0.7 to 0.9]; difference, 0.8 [95% CI, 0.6 to 1.0]; P=0.047). CONCLUSIONS: Our findings suggested that colchicine resulted in favorable effects on coronary plaque stabilization at optical coherence tomography in patients with acute coronary syndrome. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04848857.

Pinoresinol diglucoside mitigates dexamethasone-induced osteoporosis and chondrodysplasia in zebrafish.

BACKGROUND: The global increase in the aging population has led to a higher incidence of osteoporosis among the elderly. OBJECTIVE: This study aimed to evaluate the protective properties of pinoresinol diglucoside (PDG), an active constituent of Eucommia ulmoides, against dexamethasone-induced osteoporosis and chondrodysplasia. METHODS: A zebrafish model of osteoporosis was established by exposing larval zebrafish to dexamethasone. The impact of PDG on bone mineralization was assessed through alizarin red and calcein staining. Alkaline phosphatase activity was quantified to evaluate osteoblast function. The influence of PDG on chondrogenesis was estimated using alcian blue staining. Fluorescence imaging and motor behavior analysis were employed to assess the protective effect of PDG on the structure and function of dexamethasone-induced skeletal teratogenesis. qPCR determined the expression of osteogenesis and Wnt signaling-related genes. Molecular docking was used to assess the potential interactions between PDG and Wnt receptors. RESULTS: PDG significantly increased bone mineralization and corrected spinal curvature and cartilage malformations in the zebrafish model. Furthermore, PDG enhanced swimming abilities compared to the model group. PDG mitigated dexamethasone-induced skeletal abnormalities in zebrafish by upregulating Wnt signaling, showing potential interaction with Wnt receptors FZD2 and FZD5. CONCLUSION: PDG mitigates dexamethasone-induced osteoporosis and chondrodysplasia by promoting bone formation and activating Wnt signaling.

Integrated physiological, intestinal microbiota, and metabolomic responses of adult zebrafish (Danio rerio) to subacute exposure to antimony at environmentally relevant concentrations.

The available information regarding the impact of antimony (Sb), a novel environmental pollutant, on the intestinal microbiota and host health is limited. In this study, we conducted physiological characterizations to investigate the response of adult zebrafish to different environmental concentrations (0, 30, 300, and 3000 µg/L) of Sb over a period of 14 days. Biochemical and pathological changes demonstrated that Sb effectively compromised the integrity of the intestinal physical barrier and induced inflammatory responses as well as oxidative stress. Analysis of both intestinal microbial community and metabolome revealed that exposure to 0 and 30 µg/L of Sb resulted in similar microbiota structures; however, exposure to 300 µg/L altered microbial communities' composition (e.g., a decline in genus Cetobacterium and an increase in Vibrio). Furthermore, exposure to 300 µg/L significantly decreased levels of bile acids and glycerophospholipids while triggering intestinal inflammation but activating self-protective mechanisms such as antibiotic presence. Notably, even exposure to 30 µg/L of Sb can trigger dysbiosis of intestinal microbiota and metabolites, potentially impacting fish health through the "microbiota-intestine-brain axis" and contributing to disease initiation. This study provides valuable insights into toxicity-related information concerning environmental impacts of Sb on aquatic organisms with significant implications for developing management strategies.

Benzalkonium chloride induces hematopoietic stem cell reduction and immunotoxicity in zebrafish larvae.

Benzalkonium chloride (BAC) is a broad-spectrum antibacterial agent that possesses cleaning and bactericidal properties, but impact of BAC on wellbeing of aquatic organisms remains uncertain. Consequently, in this current study, we have examined the immunotoxic potential of BAC in zebrafish embryos, thus marking it as the pioneering effort in this field. According to the findings, zebrafish embryos exposed to BAC exhibited a decline in yolk area that varied with the concentration, along with a significant decrease in the count of neutrophils, macrophages, red blood cells, and thymus T-cells. We observed significantly up-regulated expression of immune-related signaling genes such as cxcl-c1c, il-8, tir4 and inf-γ, but expression of nf-κb was downregulated. In addition, we observed a marked reduction in the number of hematopoietic stem cells in zebrafish larvae after BAC exposure, which could be the result of oxidative stress-mediated apoptosis. We found that compared with the control group, the number of red blood cells in juvenile zebrafish in BAC-exposure group was significantly down-regulated, which could be attributed to hematopoietic stem cell defect. Astaxanthin restored immune cells and hematopoietic stem cells after BAC exposure, whereas Inhibitor of Wnt Response-1(IWR-1) restored neutrophils after BAC exposure. The research findings demonstrated that exposure to BAC displayed harmful effects on the development and immune system of zebrafish embryos. These effects might be associated with alterations in reactive oxygen species(ROS) levels and activation of the Wnt signaling pathway caused by BAC.

Structure, physicochemical properties, and biological activities of protein hydrolysates from Zanthoxylum seed.

BACKGROUND: Zanthoxylum seed, as a low-cost and easily accessible plant protein resource, has good potential in the food industry. But protein and its hydrolysates from Zanthoxylum seed are underutilized due to the dearth of studies on them. This study aimed to investigate the structure and physicochemical and biological activities of Zanthoxylum seed protein (ZSP) hydrolysates prepared using Protamex®, Alcalase®, Neutrase®, trypsin, or pepsin. RESULTS: Hydrolysis using each of the five enzymes diminished average particle size and molecular weight of ZSP but increased random coil content. ZSP hydrolysate prepared using pepsin had the highest degree of hydrolysis (24.07%) and the smallest molecular weight (<13 kDa) and average particle size (129.80 nm) with the highest solubility (98.9%). In contrast, ZSP hydrolysate prepared using Alcalase had the highest surface hydrophobicity and foaming capacity (88.89%), as well as the lowest foam stability (45.00%). Moreover, ZSP hydrolysate prepared using Alcalase exhibited the best hydroxyl-radical scavenging (half maximal inhibitory concentration (IC50 ) 1.94 mg mL-1 ) and ferrous-ion chelating (IC50 0.61 mg mL-1 ) activities. Additionally, ZSP hydrolysate prepared using pepsin displayed the highest angiotensin-converting enzyme inhibition activity (IC50 0.54 mg mL-1 ). CONCLUSION: These data showed that enzyme hydrolysis improved the physicochemical properties of ZSP, and enzymatic hydrolysates of ZSP exhibited significant biological activity. These results provided validation for application of ZSP enzymatic hydrolysates as antioxidants and antihypertensive agents in the food or medicinal industries. © 2023 Society of Chemical Industry.

Prognostic implication of early posttransplant hypercholesterolemia in liver transplantation for patients with hepatocellular carcinoma.

BACKGROUND: Hyperlipidemia is a common complication after liver transplantation (LT) and develops mostly in the early posttransplant period. Recently, some studies have reported a positive correlation between hyperlipidemia and favorable prognosis in patients with hepatocellular carcinoma (HCC) undergoing hepatectomy. This study aimed to evaluate the possibility of predicting prognosis in HCC patients receiving LT by early posttransplant dyslipidemia. METHODS: From January 2015 to December 2017, a total of 806 HCC patients from China Liver Transplant Registry database were retrospectively enrolled. The prognostic relevance of early posttransplant hypertriglyceridemia or hypercholesterolemia was examined using survival analysis, and subgroup analysis was implemented based on LT criteria. RESULTS: Early posttransplant hypercholesterolemia (EPHC) was independently inversely associated with the risk of recurrence [hazard ratio (HR) = 0.630; P = 0.022], but was not significantly correlated with the mortality. However, early posttransplant hypertriglyceridemia was not related to prognosis. Intriguingly, with further classification, we found that borderline EPHC (B-EPHC), instead of significant EPHC, was a predictor of lower risk for both recurrence (HR = 0.504; P = 0.006) and mortality (HR = 0.511; P = 0.023). Compared with non-EPHC patients, B-EPHC patients achieved significantly superior 1-year and 3-year tumor-free survival (89.6% and 83.7% vs. 83.8% and 72.7% respectively; P = 0.023), and 1-year and 3-year overall survival (95.8% and 84.8% vs. 94.6% and 77.6% respectively; P = 0.039). In the subgroup analysis, B-EPHC remained an independent predictor of better prognosis in patients beyond Milan criteria and those within Hangzhou criteria; whereas there was no significant relationship between B-EPHC and prognosis in patients within Milan criteria and those beyond Hangzhou criteria. More interestingly, patients beyond Milan criteria but within Hangzhou criteria were identified as the crucial subpopulation who benefited from B-EPHC (recurrence HR = 0.306, P = 0.011; mortality HR = 0.325, P = 0.031). CONCLUSIONS: B-EPHC could assist transplant teams in dynamically evaluating prognosis after LT for HCC as a postoperative non-oncological biomarker, especially in patients beyond Milan criteria but within Hangzhou criteria.

Decomposition-Reassembly Synthesis of a Silverton-Type Polyoxometalate 3D Framework: Semiconducting Properties and Photocatalytic Applications.

Polyoxometalate-based all-inorganic three-dimensional (3D) frameworks have recently attracted attention as a unique class of materials due to their unique physicochemical properties and a wide field of application with excellent prospects. We herein synthesized a novel all-inorganic 3D framework material based on cobalt-substituted Silverton-type polyoxometalate, H6{Co6W10O42[Co(H2O)4]3}·2H2O (Co9W10), which was successfully constructed using Na12[WCo3II(H2O)2(CoIIW9O34)2]·46-48H2O (Co5W19) and Co(NO3)2·6H2O as starting materials in a hydrothermal reaction via a decomposition-reassembly route together with the rational adjustment of pH values. Co9W10 has been structurally characterized using single-crystal X-ray diffraction. Photocurrent response, band-gap (Eg) value, and the VB-XPS spectrum have been measured to reveal the semiconducting property of Co9W10. Furthermore, we synthesized x% PTh/Co9W10 composites (PTh = polythiophene, x = 0.5, 1, 2, 5) for photodegradation of tetracycline hydrochloride (TH) to evaluate the photocatalytic activities of title composites. Due to the optimal molar ratio of hybrids and matching energy levels, 2% PTh/Co9W10 composites show the best photocatalytic activities among these composites.

Manipulating Liver Bile Acid Signaling by Nanodelivery of Bile Acid Receptor Modulators for Liver Cancer Immunotherapy.

Gut bacteria and their metabolites influence the immune microenvironment of liver through the gut-liver axis, thus representing emerging therapeutic targets for liver cancer therapy. However, directly manipulating gut microbiota or their metabolites is not practical in clinic since the safety concerns and the complicated mechanism of action. Considering the dysregulated bile acid profiles associated with liver cancer, here we propose a strategy that directly manipulates the primary and secondary bile acid receptors through nanoapproach as an alternative and more precise way for liver cancer therapy. We show that nanodelivery of bile acid receptor modulators elicited robust antitumor immune responses and significantly changed the immune microenvironment in the murine hepatic tumor. In addition, ex vivo stimulation on both murine and patient hepatic tumor tissues suggests the observation here may be meaningful for clinical practice. This study elucidates a novel and precise strategy for liver cancer immunotherapy.

Application of machine learning models for predicting acute kidney injury following donation after cardiac death liver transplantation.

BACKGROUND: Acute kidney injury (AKI) is a common complication after liver transplantation (LT) and is an indicator of poor prognosis. The establishment of a more accurate preoperative prediction model of AKI could help to improve the prognosis of LT. Machine learning algorithms provide a potentially effective approach. METHODS: A total of 493 patients with donation after cardiac death LT (DCDLT) were enrolled. AKI was defined according to the clinical practice guidelines of kidney disease: improving global outcomes (KDIGO). The clinical data of patients with AKI (AKI group) and without AKI (non-AKI group) were compared. With logistic regression analysis as a conventional model, four predictive machine learning models were developed using the following algorithms: random forest, support vector machine, classical decision tree, and conditional inference tree. The predictive power of these models was then evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: The incidence of AKI was 35.7% (176/493) during the follow-up period. Compared with the non-AKI group, the AKI group showed a remarkably lower survival rate (P < 0.001). The random forest model demonstrated the highest prediction accuracy of 0.79 with AUC of 0.850 [95% confidence interval (CI): 0.794-0.905], which was significantly higher than the AUCs of the other machine learning algorithms and logistic regression models (P < 0.001). CONCLUSIONS: The random forest model based on machine learning algorithms for predicting AKI occurring after DCDLT demonstrated stronger predictive power than other models in our study. This suggests that machine learning methods may provide feasible tools for forecasting AKI after DCDLT.

[Differences of Energy Spectrum CT Findings between Small Cell Lung Cancer with Mediastinal Lymph Node Metastasis and Mediastinal Sarcoidosis].

Objective To compare the differences of energy spectrum CT between small cell lung cancer(SCLC)with mediastinal lymph node metastasis and mediastinal sarcoidosis.Methods Twenty-five SCLC patients with mediastinal lymph node metastasis(SCLC group)and 26 patients with mediastinal sarcoidosis(sarcoidosis group)confirmed by bronchoscopy and biopsy in Tangshan People's Hospital from January 2018 to June 2019 were selected as the research objects.The CT value,iodine concentration,water concentration and energy spectrum curve slope under different single energy levels were compared between SCLC group and sarcoidosis group.Results The single-energy CT values of 40-80 keV segments in the arterial phase of the SCLC group were significantly higher than those in the sarcoidosis group(all P <0.05).The single-energy CT values of 90-140 keV segments were not significantly different from those in the sarcoidosis group(all P >0.05).The single-energy CT values of 40-90 keV segments in venous phase of the SCLC group were significantly higher than those of the sarcoidosis group(all P <0.05),and the single-energy CT values of 100-140 keV segments were not significantly different from those of the sarcoidosis group(all P >0.05).The concentrations of iodine in the arterial phase and venous phase of the SCLC group were(11.56±4.06)µg/cm 3 and(13.39±0.87)µg/cm 3,respectively,which were significantly higher than those [(4.43±3.85)µg/cm 3,t=11.564,P=0.026;(7.23±2.71)µg/cm 3,t=13.653,P=0.021] in the sarcoidosis group.The concentrations of water in the arterial and venous phases of the SCLC group were(1040.67±5.62)mg/cm 3 and(1035.23±8.57)mg/cm 3,respectively,which showed no statistically significant difference compared with those [(1028.87±6.94)mg/cm 3,t=3.155,P=1.861;(1021.53±4.68)mg/cm 3,t=3.265,P=1.687] in the sarcoidosis group.The slopes of energy spectrum curve at 40-70 keV,70-100 keV and 100-140 keV in venous phase of the SCLC group were significantly higher than those of the sarcoidosis group(all P <0.05),whereas they showed no significant difference between the two groups in arterial phase(all P >0.05).Conclusion The differences between SCLC with mediastinal lymph node metastasis and mediastinal sarcoidosis can be shown on the single-energy CT values of 40-80 keV in arterial phase and 40-90 keV in venous phase,iodine concentrations in arterial phase and venous phase,and the slope of energy spectrum curve in venous phase.

[Herbalogical analysis of Aconiti Carmichaeli Radix].

Tianxiong has been used as a Chinese medicinal in China for thousands of years, and the earliest record can be traced back to the Shennong's Classic of Materia Medica. It is effective in dispersing wind, dissipating cold, and replenishing fire to streng-then yang. To clarify the origin of Tianxiong, the present herbalogical study reviewed the ancient and modern literature from the origin, processing, and clinical efficacy. Before the Tang Dynasty, although the description of Tianxiong was quite superficial, an apparent difference between Tianxiong and Fuzi was recognized. In the Tang and Song Dynasties, Tianxiong and Fuzi were mistakenly recognized to be prepared from a same plant since their raw materials came from artificial cultivation. Medical literature in the Ming and Qing Dynasties mostly followed the previous records, with the origin of Tianxiong remaining controversial. There were three mainstream views about the origin of Tianxiong according the ancient medical books. First, Tianxiong was a kind of Aconiti Radix(Chuanwu) without attachment of Fuzi. Second, Tianxiong was the large Fuzi. Third, Tianxiong derived from Aconiti Kusnezoffii Radix(Caowu) about 10 cm in length. By contrast, Fuzi in a large size was simply regarded as Tianxiong in modern times. The processing methods were diversified in the ancient times, and the fire-processing was continuously applied. With the deepening of the research on the efficacy and detoxification mechanism, more methods were discovered, such as processing with ginger juice, child's urine and alcohol. As for modern times, the processing of Tianxiong has not been nearly passed down. The characteristic processing of Tianxiong only handed down in Sichuan province and Lingnan area, which can be discriminated by the last step. The efficacies of Tianxiong can be directly understood from its literal name, including dispersing wind, dissipating cold, and replenishing fire to assist yang. Nowadays, Tianxiong is mostly used to strengthen yang.

[Different Energy Spectrum CT Findings between Anterior Mediastinal Lymphoma and Thymic Carcinoma].

Objective To investigate the differences in energy spectrum CT findings between anterior mediastinal lymphoma and thymic carcinoma. Methods Twenty-two cases of anterior mediastinal lymphoma and 28 cases of thymic carcinoma confirmed by biopsy in Tangshan People's Hospital were selected.The CT values and changes of iodine content and water content in lesion sites were measured by energy spectrum analysis software.The differences between anterior mediastinal lymphoma and thymic carcinoma were compared. Results The single-energy CT value of 40-80 keV in thymus carcinoma was higher than that in anterior mediastinal lymphoma(P=0.001,P=0.037,P=0.042,P=0.034,P=0.002;P=0.016,P=0.013,P=0.018,P=0.024,P=0.012).The difference in the single-energy CT value of 90-110 keV between anterior mediastinal lymphoma and thymic carcinoma showed no statistical significance(all P>0.05).The concentrations of water in the arterial and venous stages of thymic carcinoma were significantly lower than those in the anterior mediastinal lymphoma(P=0.030,P=0.037),whereas the iodine concentrations were significantly higher(P=0.026,P=0.000). Conclusion Anterior mediastinal lymphoma and thymic carcinoma have remarkably different 40-80 keV single energy CT value and iodine concentration in arterial and venous phases,which may be helpful for the differential diagnosis of these two malignancies.

Regulation of gammaherpesvirus lytic replication by endoplasmic reticulum stress-induced transcription factors ATF4 and CHOP.

The stress-induced unfolded protein response (UPR) in the endoplasmic reticulum (ER) involves various signaling cross-talks and controls cell fate. B-cell receptor (BCR) signaling, which can trigger UPR, induces gammaherpesvirus lytic replication and serves as a physiological mechanism for gammaherpesvirus reactivation in vivo However, how the UPR regulates BCR-mediated gammaherpesvirus infection is unknown. Here, we demonstrate that the ER stressors tunicamycin and thapsigargin inhibit BCR-mediated murine gammaherpesvirus 68 (MHV68) lytic replication by inducing expression of the UPR mediator Bip and blocking activation of Akt, ERK, and JNK. Both Bip and the downstream transcription factor ATF4 inhibited BCR-mediated MHV68 lytic gene expression, whereas UPR-induced C/EBP homologous protein (CHOP) was required for and promoted BCR-mediated MHV68 lytic replication by suppressing upstream Bip and ATF4 expression. Bip knockout was sufficient to rescue BCR-mediated MHV68 lytic gene expression in CHOP knockout cells, and this rescue was blocked by ectopic ATF4 expression. Furthermore, ATF4 directly inhibited promoter activity of the MHV68 lytic switch transactivator RTA. Altogether, we show that ER stress-induced CHOP inhibits Bip and ATF4 expression and that ATF4, in turn, plays a critical role in CHOP-mediated regulation of BCR-controlled MHV68 lytic replication. We conclude that ER stress-mediated UPR and BCR signaling pathways are interconnected and form a complex network to regulate the gammaherpesvirus infection cycle.

Serum deprivation response functions as a tumor suppressor gene in papillary thyroid cancer.

The mechanism of papillary thyroid cancer (PTC) has shown numerous recurrently mutated genes, but the discovery of abnormal expression of novel tumor suppressor genes has been slow. The aim of our study is to explore the biological functions of SDPR in thyroid cancer. We reanalyzed the RNA-Seq data of PTC from The Cancer Genome Atlas (TCGA) database and found that serum deprivation response (SDPR) was significantly downregulated in PTC. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was performed to assess the expression of SDPR. Both loss- and gain-of-function experiments, and flow cytometry were performed to investigate the functions. SDPR was significantly downregulated in PTC. Reduced expression of SDPR was associated with larger tumor size, more serious lymph node metastasis, and advanced American Joint Committee on Cancer (AJCC) stage. Patients with lower SDPR expression had a shorter recurrence-free survival. SDPR expression and AJCC stage were independent predictors of poor recurrence-free survival (RFS). Moreover, cell proliferation, colony formation, and migration were inhibited after SDPR overexpression, whereas knockdown of SDPR exerted an oncogenic effect. SDPR induction also initiated the mesenchymal-epithelial transition, alongside suppressing AKT signaling and cyclin family expression. Apart from DNA methylation, LOC105373813, may also co-regulate SDPR expression by forming a stable hybrid with SDPR messenger RNA. Our study indicated that SDPR may function as a potential prognostic marker in PTC.

MiR-26a functions as a tumor suppressor in ambient particulate matter-bound metal-triggered lung cancer cell metastasis by targeting LIN28B-IL6-STAT3 axis.

Exposure to ambient particulate matter (PM) has been linked to the increasing incidence and mortality of lung cancer, but the principal toxic components and molecular mechanism remain to be further elucidated. In this study, human lung adenocarcinoma A549 cells were treated with serial concentrations of water-extracted PM10 (WE-PM10) collected from Beijing, China. Our results showed that exposure to 25 and 50 µg/ml of WE-PM10 for 48 h significantly suppressed miR-26a to upregulate lin-28 homolog B (LIN28B), and in turn activated interleukin 6 (IL6) and signal transducer and activator of transcription 3 (STAT3) in A549 cells, subsequently contributing to enhanced epithelial-mesenchymal transition and accelerated migration and invasion. In vivo pulmonary colonization assay further indicated that WE-PM10 enhanced the metastatic ability of A549 cells. In addition, luciferase reporter assay demonstrated that 3' untranslated region of LIN28B was a direct target of miR-26a. Last but not the least, the key toxic contribution of metals in WE-PM10 was confirmed by the finding that removal of metals through chelation significantly rescued WE-PM10-mediated inflammatory, carcinogenic and metastatic responses. Taken together, miR-26a could act as the tumor suppressor in PM10-related lung cancer, and PM10-bound metals promoted lung cancer cell metastasis through downregulation of miR-26a that directly mediated LIN28B expression.

New-onset hyperglycemia immediately after liver transplantation: A national survey from China Liver Transplant Registry.

BACKGROUND: New-onset hyperglycemia (NOH) is a common phenomenon after liver transplantation (LT), but its impact on clinical outcomes has not yet been fully assessed. We aimed to evaluate the etiology and prognosis of NOH within 1 month after LT. METHODS: The data of 3339 adult patients who underwent primary LT from donation after citizen death between January 2010 and June 2016 were extracted from China Liver Transplant Registry database and analyzed. NOH was defined as fasting blood glucose ≥7.0 mmol/L confirmed on at least two occasions within the first post-transplant month with or without hypoglycemic agent. RESULTS: Of 3339 liver recipients, 1416 (42.4%) developed NOH. Recipients with NOH had higher incidence of post-transplant complications such as graft and kidney failure, infection, biliary stricture, cholangitis, and tumor recurrence in a glucose concentration-dependent manner as compared to non-NOH recipients (P < 0.05). The independent risk factors of NOH were donor warm ischemic time >10 min, cold ischemic time >10 h, anhepatic time >60 min, recipient model for end-stage liver disease score >30, moderate ascites and corticosteroid usage (P < 0.05). Liver enzymes (alanine aminotransferase and gamma-glutamyltranspeptidase) on post-transplant day 7 significantly correlated with NOH (P < 0.001). CONCLUSIONS: NOH leads to increased morbidity and mortality in liver recipients. Close surveillance and tight control of blood glucose are desiderated immediately following LT particularly in those with delayed graft function and receiving corticosteroid. Strategic targeting graft ischemic injury may help maintain glucose homeostasis.

Examine the Correlation between Heat Shock Protein IbpA and Heat Tolerance in Cronobacter sakazakii.

We used a proteomic approach to identify IbpA in Cronobacter sakazakii (C. sakazaki), which is related to heat tolerance in this strain. The abundance of IbpA in C. sakazakii strains strongly increased after heat shock. C. sakazakii CMCC 45402 ibpA deletion mutants were successfully constructed. The C. sakazakii CMCC 45402 ΔibpA and wild-type strains could not be distinguished based on colony morphology on LB agar plates or biochemical assays. The growth of the C. sakazakii CMCC 45402 ΔibpA mutant in heat shock conditions was indistinguishable from that of the isogenic wild-type, but showed greater heat resistance than E. coli O157:H7 strain CMCC 44828. This study suggests that the absence of a single ibpA gene has no obvious effect on the phenotype or heat resistance of the strain C. sakazakii CMCC 45402.

A novel long non-coding RNA FGF14-AS2 is correlated with progression and prognosis in breast cancer.

Breast cancer is diverse in their natural history and in their responsiveness to treatments. It is urgent to generate candidate biomarkers for the stratification of patients and personalization of therapy to avoid overtreatment or inadequate treatment. Long noncoding RNAs (lncRNAs) have been found to be pervasively transcribed in the genome and played critical roles in cancer progression. A lot of lncRNAs have been reported as potential prognostic biomarkers and therapeutic targets in multiple cancers. In this study, we demonstrated that FGF14 antisense RNA 2 (FGF14-AS2), a novel long non-coding RNA, was significantly down-regulated in breast cancer tissue compared with adjacent normal tissue both in validated cohort and TCGA cohort. Reduced expression of FGF14-AS2 was correlated with larger tumor size, more lymph node metastasis and advanced clinical stage in both cohorts. Kaplan-Meier analysis indicated that patients with lower FGF14-AS2 expression had a worse overall survival. Moreover, multivariate analysis revealed that decreased expression of FGF14-AS2 was an independent predictor of overall survival. Together, these results suggested that FGF14-AS2 involved in the progress of breast cancer and might act as a tumor suppressor gene. To the best of our knowledge, it was firstly reported that FGF14-AS2 was involved in cancer. This study provided a potential new marker and a target for gene therapy in breast cancer treatment.

Upregulation of CD44v6 contributes to acquired chemoresistance via the modulation of autophagy in colon cancer SW480 cells.

The CD44 isoform containing variant exon v6 (CD44v6) plays an important role in the progression, metastasis, and prognosis of colorectal cancer (CRC). Recently, it was found that CD44v6 is involved in acquired drug resistance. This study aimed to investigate the molecular mechanism of CD44v6 in the resistance of CRC cells to chemotherapy. A stable CD44v6 overexpression model in SW480 cells was established via lentiviral transduction. The chemosensitivity of cells to 5-fluorouracil (5-FU) and oxaliplatin (L-OHP) was determined by cell counting kit (CCK)-8, lactate dehydrogenase (LDH) release, and colony formation assays. Immunohistochemical staining of CD44v6 was performed in human CRC tissues. The key components in cell apoptosis, drug efflux and metabolism, mismatch repair, autophagy, epithelial-mesenchymal transition (EMT), and the PI3K-Akt and MAPK-Ras-Erk1/2 pathways were assessed using flow cytometry, quantitative real-time polymerase chain reaction (PCR), and western blot assays. The CD44v6 overexpression cells showed a higher viability, a lower LDH release rate, and an increased clonogenicity than the control cells under drug treatment. Moreover, overexpression of CD44v6 resulted in enhanced autophagy flux, EMT, and phosphorylation of Akt and Erk in the presence of drugs. Furthermore, high CD44v6 expression in the primary tumor was closely associated with an early recurrence in CRC patients who underwent curative surgery and adjuvant chemotherapy. In conclusion, overexpression of CD44v6 contributes to chemoresistance in SW480 cells under cytotoxic stress via the modulation of autophagy, EMT, and activation of the PI3K-Akt and MAPK-Ras-Erk pathways.