PINK1/Park2-Mediated Mitophagy Relieve Non-Alcoholic Fatty Liver Disease.

Up to now, there's a limited number of studies on the relationship between PINK1/Park2 pathway and mitophagy in NAFLD. To investigate the effect of Park2-mediated mitophagy on non-alcoholic fatty liver disease (NAFLD). Oleic acid was used for the establishment of NAFLD model. Oil red-dyed lipid drops and mitochondrial alternations were observed by transmission electron microscopy. Enzymatic kit was used to test lipid content. The levels of IL-8 and TNF-alpha were determined by ELISA. Lenti-Park2 and Park2-siRNA were designed to upregulate and downregulate Park2 expression, respectively. The changing expression of PINK and Park2 was detected by RT-qPCR and Western blot. Immunofluorescence staining was applied to measure the amount of LC3. Successful NAFLD modeling was featured by enhanced lipid accumulation, as well as the elevated total cholesterol (TC), triglyceride (TG), TNF-alpha and IL-8 levels. Mitochondria in NAFLD model were morphologically and functionally damaged. Park2 expression was upregulated by lenti-Park2 and downregulated through Park2-siRNA. The PINK1 expression showed the same trend as Park2 expression. Immunofluorescence staining demonstrated that the when Park2 was overexpressed, more LC3 protein on mitochondrial autophagosome membrane was detected, whereas Park2 knockdown impeded LC3' locating on the membrane. The transmission electron microscopy image exhibited that the extent of damage to the mitochondrial in NAFLD model was revered by enhanced Park2 expression but further exacerbated by reduced Park2 expression. Park2-mediated mitophagy could relive NAFLD and may be a novel therapeutic target for NAFLD treatment. Keywords: Non-alcoholic Fatty Liver Disease (NAFLD), Mitophagy, PINK1/Park2, Park2, PINK1.

[Investigation on status of lung cancer cough management and concept and practice of lung cancer cough management in Chinese medical providers].

Objective: Investigate the current situation of lung cancer cough diagnosis and treatment and the awareness of related issues among Chinese medical providers. Methods: Doctors, nurses, pharmacists from the oncology department, respiratory department, or general department were investigated using an electronic questionnaire from January 29 to March 29, 2021. There were 25 questions about lung cancer in the questionnaire. The questionnaire was including the most common accompanying symptoms in patients with lung cancer, the incidence of lung cancer-related cough, the assessment of the proportion of central antitussive drugs, and the commonly used central antitussives. Results: Questionnaires from 2 424 medical providers were collected from 402 hospitals in 21 provincial administrative units. Cough was the most common symptom in lung cancer. Most physicians believed that the incidence of lung cancer-related cough was 51%~75%, while the proportion of patients satisfied with the treatment was only 11%~20%. The evaluation of lung cancer-related cough was seriously insufficient. The leading cause of lung cancer-related cough was tumors. And the main problem was the inadequate antitussive effect of drugs in lung cancer-related cough management. The proportion of central antitussive medication usage in the secondary and tertiary hospitals was 93.9% and 92.0%, significantly higher than 75.0% in Primary hospitals (χ²=8.390, P=0.015). The proportion of the physicians who underhanded that codeine is at risk of addiction was 76.6% and 72.0% in the secondary and tertiary hospitals, which were significantly higher than 53.9% in Primary hospitals (χ²=9.240, P=0.010). In different occupations, the proportions of doctors and pharmacists who knew the risk of addicting to codeine were 73.0% and 82.6%, which were significantly higher than the 66.4% of nurses (χ²=21.200, P<0.001). The Chinese medical providers were lack of training about the basic knowledge of using central antitussive medication. Conclusions: The proportion of patients who were satisfied with the effect of cough treatment is low. The medical staff did not have enough awareness of this. There was an urgent need to develop a consensus and standardize lung cancer cough diagnosis and treatment in China.

Phosphatidic acid and hydrogen peroxide coordinately enhance heat tolerance in tall fescue.

Phosphatidic acid (PA) and hydrogen peroxide (H2 O2 ) play roles in regulating plant responses to abiotic stress. The objective of this study was to determine effects of H2 O2 or PA, individually and interactively, with a H2 O2 scavenging molecule, N,N'-dimethylthoiurea (DMTU), on plant tolerance to heat stress in tall fescue (Festuca arundinacea). Plants were treated with PA (25 µm), H2 O2 (5 mm) and PA (25 µm) + DMTU (5 mm) by foliar application and then exposed to heat stress (38/33 °C) or optimal temperature (23/18 °C, day/night) for 28 days. Foliar application of PA and H2 O2 alone resulted in increases in leaf fresh weight, chlorophyll content, photochemical efficiency and cellular membrane stability in plants exposed to heat stress, whereas addition of DMTU suppressed the positive effects of PA. Expression levels of genes encoding the PA synthesizing enzyme, FaPLDδ, were significantly up-regulated by H2 O2 . Phosphatidic acid- or H2 O2 -enhanced heat tolerance was associated with the activation of stress signalling components (FaCDPK3, FaMPK6, FaMPK3), transcription factors (FaMBF1 and FaHsfA2c) and heat shock proteins (FaHSP18, FaHSP70 and FaHSP90). Phosphatidic acid and H2 O2 may work in coordination to further improve heat tolerance, involving up-regulation of transcription factors in stress signalling cascades and heat protection systems.

Circular RNA circHIPK3 serves as a prognostic marker to promote chronic myeloid leukemia progression.

Increasing evidence demonstrate that circular RNAs (circRNAs) play critical role in regulation of gene expression, which participate in the pathogenesis of cancer, including chronic myeloid leukemia (CML). In this study, we aimed to investigate the expression profiling of circHIPK3 in CML. We found that circHIPK3 was significantly upregulated in peripheral blood mononuclear cells (PBMC) and serum samples from CML compared with healthy controls. High circHIPK3 expression predicted a poor outcome of CML patients. Further loss-function experiments suggested the oncogenic role of circHIPK3 in CML. Our findings provide insights on the role of circHIPK3 in the development and treatment of CML.

Considerations for Dose Selection and Clinical Pharmacokinetics/Pharmacodynamics for the Development of Antibacterial Agents.

In June 2017, The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, organized a workshop entitled "Pharmacokinetics-Pharmacodynamics (PK/PD) for Development of Therapeutics against Bacterial Pathogens" to discuss details and critical parameters of various PK/PD methods and identify approaches for linking human pharmacokinetic (PK) data and drug efficacy analyses. The workshop participants included individuals from academia, industry, and government. This and the accompanying minireview on nonclinical PK/PD summarize the workshop discussions and recommendations. It is important to consider how information like PK/PD can support the clinical effectiveness of new antibacterial drugs, as PK/PD data have become central to antibacterial drug development programs. Key clinical considerations for antibacterial dose selection and clinical PK/PD characterization discussed in this minireview include a robust assessment of PK in the patient population of interest, critical considerations for assessing drug penetration in the lung for the treatment of pneumonia, and an emphasis on special populations, including patients with renal impairment and augmented renal function, as well as on dosing in obese and pediatric patients. Successful application of such approaches is now used to provide a more informative drug development package to support the approval of new antibiotics.

[Genetic characteristic of hemagglutinin of avian influenza A (H7N9) virus in Guizhou Province in 2017].

The number of H7N9 bird flu cases was high and the situation was grim in guizhou province in 2017. To understand the molecular characteristics of the hemagglutinin gene (HA) and the risk of human infection with avian influenza virus A(H7N9) in Guizhou Province, 2017. Homology, genetic evolution and pivotal sites related to receptor binding regions, pathogenicity and potential glycosylation of 14 avian influenza viruses A(H7N9) were analyzed by a series of bioinformation softwares. It was cleared that there was 95.9%-100% similarity among 14 strains in nucleotide of the HA gene, and there were 96.8%-97.8% and 96.8%-97.9% similarities with vaccine strains A/Shanghai/2/2013 and A/Anhui/1/2013 recommended by WHO, respectively. Phylogenetic analysis showed that 14 HA genes were directly evolved in the Yangtze River Delta evolution branch, but they could be derived from five diffenrent strains. Then 13 of 14 strains cleavage site sequences of HA protein revealed they were low pathogenic avian influenza viruses, while A/Guizhou-Weining/CSY01/2017 was high pathogenic avian influenza virus. Mutation G186V at the receptor binding sites in the HA was found in all 14 strains, and mutation Q226L in 13 strains besides A/Guizhou-Weining/CSY01/2017. All five potential glycosylation motifs in the HA were conservative.

A model-based analysis of pharmacokinetic-pharmacodynamic (PK/PD) indices of avibactam against Pseudomonas aeruginosa.

OBJECTIVE: The aim of the present work was to use a semi-mechanistic pharmacokinetic-pharmacodynamic (PK/PD) model developed from in vitro time-kill measurements with P. aeruginosa to compare different pharmacodynamic indices derived from simulated human avibactam exposures, with respect to their degree of correlation with the modelled bacterial responses. METHODS: A mathematical model of the effect of ceftazidime-avibactam on the growth dynamics of P. aeruginosa was used to simulate bacterial responses to modelled human exposures from fractionated avibactam dosing regimens with a fixed ceftazidime dosing regimen (2 or 8 g q8h as a 2-h infusion). The relatedness of the 24-h change in bacterial density and avibactam exposure parameters was evaluated to determine exposure parameter that closely correlated with bacterial growth/killing responses. RESULTS: Frequent dosing was associated with higher efficacy, resulting in a reduction of avibactam daily dose. The best-fit PD index of avibactam determined from the simulation was fT > CT of 1 mg/L avibactam and q8h was the longest dosing interval able to achieve 2-log kill: 41-87% (3.3 h to 7.0 h out of 8-h interval, respectively). The avibactam exposure magnitude required to achieve a 2-log kill in the simulations was dependent on the susceptibility of the bacterial isolate to ceftazidime. CONCLUSIONS: Avibactam activity in combination with ceftazidime against multidrug resistant P. aeruginosa correlated with fT > CT. Setting a threshold avibactam concentration to 1 mg/L, superimposed over a simulated human-like exposure of ceftazidime, achieved at least 2-log kill for the clinical dose of 500 mg q8h avibactam as a 2-h infusion, depending on the minimum inhibitory concentration of ceftazidime alone.

[Genetic characteristics of hemagglutinin and neuraminidase of avian influenza A (H7N9) virus in Guizhou province, 2014-2017].

Objective: To understand the molecular characteristics of hemagglutinin (HA) and neuraminidase (NA) as well as the disease risk of influenza virus A H7N9 in Guizhou province. Methods: RNAs were extracted and sequenced from HA and NA genes of H7N9 virus strains obtained from 18 cases of human infection with H7N9 virus and 6 environmental swabs in Guizhou province during 2014-2017. Then the variation and the genetic evolution of the virus were analyzed by using a series of bioinformatics software package. Results: Homology analysis of HA and NA genes revealed that 2 strains detected during 2014-2015 shared 98.8%-99.2% and 99.2% similarities with vaccine strains A/Shanghai/2/2013 and A/Anhui/1/2013 recommended by WHO, respectively. Two strains detected in 2016 and 14 strains detected in 2017 shared 98.2%-99.3% and 97.6%-98.8% similarities with vaccine strain A/Hunan/02650/2016, respectively. Other 6 stains detected in 2017 shared 99.1%-99.4% and 98.9%-99.3% similarities with strain A/Guangdong/17SF003/2016, respectively. Phylogenetic analysis showed that all the strains were directly evolved in the Yangtze River Delta evolution branch, but they were derived from different small branch. PEVPKRKRTAR↓GLF was found in 6 of 24 strains cleavage site sequences of HA protein, indicating the characteristic of highly pathogenic avian influenza virus. Mutations A134V, G186V and Q226L at the receptor binding sites were found in the HA. All the strains had a stalk deletion of 5 amino acid residue "QISNT" in NA protein, and drug resistance mutation R294K occurred in strain A/Guizhou-Danzhai/18980/2017. In addition, potential glycosylation motifs mutations NCS42NCT were found in the NA of 9 of 24 strains. Conclusions: HA and NA genes of avian influenza A (H7N9) virus showed genetic divergence in Guizhou province during 2014-2017. The mutations of key sites might enhance the virulence of the virus, human beings are more susceptible to it. Hence, the risk of infection is increasing.

The role of Parkin protein in cardiac function and ventricular remodeling in myocardial infarction rats.

OBJECTIVE: This study aims to explore the role and the mechanism of Parkin protein in cardiac function and ventricular remodeling in myocardial infarction (MI) rats, and to provide a new sight for the treatment of myocardial infarction. MATERIALS AND METHODS: Fifty Sprague- Dawley (SD) male rats were randomly divided into 5 groups: sham operation group (Sham group), model group (MI group), low-dose Parkin group (L-Parkin group), middle-dose Parkin group (M-Parkin group) and high-dose Parkin group (H-Parkin group). The rat model of myocardial infarction was established by ligation of the anterior descending branch. Small animal ultrasound was used to measure cardiac function. The myocardial infarct size was observed by triphenyltetrazolium chloride (TTC) staining. The pathological changes of myocardial tissues were observed by hematoxylin-eosin (HE) staining. The myocardial cell apoptosis was detected by TUNEL assay. The mRNA expression of matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), tissue inhibitor of matrix metalloproteinase 1 (TIMP1), tissue inhibitor of matrix metalloproteinase 2 (TIMP2) were detected by qRT-PCR. The expression of Parkin protein in myocardial tissue of rats was detected by Western-blot. RESULTS: Compared with MI group, left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV) in Parkin overexpressing group were significantly decreased (p<0.05), while the value of left ventricular short axis shortening (FS) and left ventricular ejection fraction (EF %) in Parkin overexpression group were significantly increased (p<0.05). Overexpression of Parkin improved abnormal structure of myocardial tissue, reduced the size of myocardial infarct, made the arrangement of myocardium fibers more neatly and made the stain of myocardial cells more uniformly. Apoptosis index (AI) values were significantly decreased (p<0.05), and MMP2, MMP9, TIMP1 and TIMP2 mRNA levels were significantly decreased (p<0.05), while Parkin protein expression was significantly elevated in a dose-dependent manner (p<0.05). CONCLUSIONS: After treatment with Parkin in myocardial infarction rats, the relevant mRNA levels decreased, the number of apoptotic cells decreased, the myocardial fiber morphology returned to normal, the myocardial infarct size decreased, and the cardiac function of rats improved. Therefore, Parkin therapy plays an active role in cardiac function and ventricular remodeling in myocardial infarction rats.

Author Correction: Magnetism and high magnetic-field-induced stability of alloy carbides in Fe-based materials.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Magnetism and high magnetic-field-induced stability of alloy carbides in Fe-based materials.

Understanding the nature of the magnetic-field-induced precipitation behaviors represents a major step forward towards unravelling the real nature of interesting phenomena in Fe-based alloys and especially towards solving the key materials problem for the development of fusion energy. Experimental results indicate that the applied high magnetic field effectively promotes the precipitation of M23C6 carbides. We build an integrated method, which breaks through the limitations of zero temperature and zero external field, to concentrate on the dependence of the stability induced by the magnetic effect, excluding the thermal effect. We investigate the intimate relationship between the external field and the origins of various magnetics structural characteristics, which are derived from the interactions among the various Wyckoff sites of iron atoms, antiparallel spin of chromium and Fe-C bond distances. The high-magnetic-field-induced exchange coupling increases with the strength of the external field, which then causes an increase in the parallel magnetic moment. The stability of the alloy carbide M23C6 is more dependent on external field effects than thermal effects, whereas that of M2C, M3C and M7C3 is mainly determined by thermal effects.

Revisiting the horizontal redistribution of water in soils: Experiments and numerical modeling.

A series of experiments and related numerical simulations were carried out to study one-dimensional water redistribution processes in an unsaturated soil. A long horizontal Plexiglas box was packed as homogenously as possible with sand. The sandbox was divided into two sections using a very thin metal plate, with one section initially fully saturated and the other section only partially saturated. Initial saturation in the dry section was set to 0.2, 0.4, or 0.6 in three different experiments. Redistribution between the wet and dry sections started as soon as the metal plate was removed. Changes in water saturation at various locations along the sandbox were measured as a function of time using a dual-energy gamma system. Also, air and water pressures were measured using two different kinds of tensiometers at various locations as a function of time. The saturation discontinuity was found to persist during the entire experiments, while observed water pressures were found to become continuous immediately after the experiments started. Two models, the standard Richards equation and an interfacial area model, were used to simulate the experiments. Both models showed some deviations between the simulated water pressures and the measured data at early times during redistribution. The standard model could only simulate the observed saturation distributions reasonably well for the experiment with the lowest initial water saturation in the dry section. The interfacial area model could reproduce observed saturation distributions of all three experiments, albeit by fitting one of the parameters in the surface area production term.

Prediction of in vivo and in vitro infection model results using a semimechanistic model of avibactam and aztreonam combination against multidrug resistant organisms.

The combination of aztreonam-avibactam is active against multidrug-resistant Enterobacteriaceae that express metallo-ß-lactamases. A complex synergistic interaction exists between aztreonam and avibactam bactericidal activities that have not been quantitatively explored. A two-state semimechanistic pharmacokinetic/pharmacodynamic (PK/PD) logistic growth model was developed to account for antimicrobial activities in the combination of bacteria-mediated degradation of aztreonam and the inhibition of aztreonam degradation by avibactam. The model predicted that changing regimens of 2 g aztreonam plus 0.375 and 0.6 g avibactam as a 1-hour infusion were qualitatively similar to that observed from in vivo murine thigh infection and hollow-fiber infection models previously reported in the literature with 24-hour log kill ≥1. The current approach to characterize the effect of avibactam in enhancing aztreonam activity from time-kill study was accomplished by shifting the half-maximal effective concentration (EC50 ) of aztreonam in increasing avibactam concentration using a nonlinear equation as a function of avibactam concentration, providing a framework for translational predictions.

Otolith shape lends support to the sensory drive hypothesis in rockfishes.

The sensory drive hypothesis proposes that environmental factors affect both signalling dynamics and the evolution of signals and receivers. Sound detection and equilibrium in marine fishes are senses dependent on the sagittae otoliths, whose morphological variability appears intrinsically linked to the environment. The aim of this study was to understand if and which environmental factors could be conditioning the evolution of this sensory structure, therefore lending support to the sensory drive hypothesis. Thus, we analysed the otolith shape of 42 rockfish species (Sebastes spp.) to test the potential associations with the phylogeny, biological (age), ecological (feeding habit and depth distribution) and biogeographical factors. The results showed strong differences in the otolith shapes of some species, noticeably influenced by ecological and biogeographical factors. Moreover, otolith shape was clearly conditioned by phylogeny, but with a strong environmental effect, cautioning about the use of this structure for the systematics of rockfishes or other marine fishes. However, our most relevant finding is that the data supported the sensory drive hypothesis as a force promoting the radiation of the genus Sebastes. This hypothesis holds that adaptive divergence in communication has significant influence relative to other life history traits. It has already been established in Sebastes for visual characters and organs; our results showed that it applies to otolith transformations as well (despite the clear influence of feeding and depth), expanding the scope of the hypothesis to other sensory structures.

DCD liver transplant infection: experience from a single centre in China.

AIM: The purpose of our study was to evaluate the incidence, timing, location and risk factors for bacterial and fungal infections after donation after cardiac death (DCD) liver transplant and clearly delineate any relationship between infection and survival in DCD liver transplant recipients. METHODS: We retrospectively reviewed 257 consecutive patients undergoing DCD liver transplant between October 2010 and May 2015 at our centre. RESULTS: A total of 133 patients (51.8%) developed at least one bacterial or fungal infection episode. The predominant infection site was the respiratory tract, followed by the blood stream. Most of the infections occurred within the first week after liver transplant (61.9%). A recipient respiratory support time greater than 7 days (p = 0.041), post-transplant hospital time greater than 24 days (p = 0.002) and renal failure after DCD liver transplant (p = 0.039) were independent predictors of bacterial and fungal infection. The area under the receiver operating characteristic (ROC) curve (AUC) of the transplant infection risk assessment model was 0.788. The 1- and 3-year survival rates for recipients without infection were significantly increased compared with recipients with infection (96.1% and 89.0% vs. 81.5% and 75.9%, p = 0.007). CONCLUSION: This is the first study that offers detailed data revealing the timing and incidence of bacterial and fungal infection among adult DCD liver transplant recipients. Bacterial and fungal infection occurs at a high rate during the first week after DCD liver transplant, especially in patients with prolonged respiratory support time and renal failure, and infection is related to increased hospital stay.

Peripheral blood CD4(+) cell ATP activity measurement to predict HCC recurrence post-DCD liver transplant.

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) recurrence after orthotopic liver transplantation (OLT) continues to confound transplant surgeons and physicians. There are no effective methods to predict the patients at risk for recurrence so far although many studies have sought meaningful biomarkers. The ImmuKnow (IMK) assay is an immune cell function assay that detects cell-mediated immunity in an immunosuppressed population, mainly measuring peripheral blood CD4(+) adenosine triphosphate (ATP) release. The aim of this study was to assess the relationship between cellular immune function measured by the ImmuKnow assay and HCC recurrence post-OLT. METHODS: A total of 76 HCC cases underwent Donation after Cardiac Death (DCD) liver transplant, which confirmed hepatocellular carcinoma by histology postoperatively. The ImmuKnow assay was prospectively performed in these cases at a range of 6-36 months post-OLT. Every test was repeated 1 week later, obtaining the average value for every patient. In addition, every case had liver imaging findings at approximately the exam time. RESULTS: Fifteen cases with liver imaging findings showed HCC recurrence (19.7%) post-OLT, and the average ImmuKnow assay in these patients was 190 ± 48 ng/ml, which was less (p < 0.05) than in patients without HCC recurrence, whose average ATP level was 313 ± 90 ng/ml. ATP levels post-OLT were found to be significantly associated with the risk of tumour recurrence. The ratio of T reg cells and the levels of TGFß and IL-10 were higher in recurrence patients than in recurrence-free patients. CONCLUSION: Greater suppression of cellular immunity, as measured by the ImmuKnow assay, was associated with progression of HCC recurrence post-OLT. ImmuKnow assay was helpful in determining the risk of early recurrence of HCC postliver transplant. A pathway consisting of T reg cells, TGFß and IL-10 might be the HCC recurrence-predominant pathway.

Prevalence, resistance patterns, and characterization of integrons of Shigella flexneri isolated from Jiangsu Province in China, 2001-2011.

OBJECTIVE: To provide the epidemiology, resistance pattern, and characterization of integrons in Shigella flexneri isolated between 2001 and 2011 in Jiangsu Province. METHOD: A total of 624 strains of S. flexneri were collected from both outpatients and inpatients in hospitals in Jiangsu Province from January 2001 to December 2011. The Kirby-Bauer disk diffusion method was used to perform the antimicrobial susceptibility test. Polymerase chain reaction (PCR) was used in the detection of integrons. Pulsed-field gel electrophoresis (PFGE) was applied in the homology studies. RESULT: Serotype 2a accounted for the largest proportion in S. flexneri, namely 26.4 %. Notably, an increasing trend was detected in the resistance to common antimicrobial agents during the period 2001-2011. In recent years, more than 80.0 % isolates of S. flexneri have proved to be resistant to ampicillin, nalidixic acid, and tetracycline. The positive rates of class 1, class 2, and the atypical class 1 integrons in S. flexneri are 69.3 %, 87.8 %, and 89.2 % respectively. Most integrons detected in our research carry genes encoding resistance to trimethoprim and streptomycin. CONCLUSION: Antimicrobial resistance in S. flexneri has demonstrated a continuous rising trend in Jiangsu Province. A high prevalence of integrons and gene cassettes play an important role in the transmission of drug resistance in S. flexneri. Effective measures are urgently needed to control the spread of multi-drug-resistant S. flexneri, and more continuing active surveillance of antimicrobial resistance should be established worldwide, especially in developing countries.

MicroRNA-92b promotes hepatocellular carcinoma progression by targeting Smad7 and is mediated by long non-coding RNA XIST.

MicroRNA (miRNA) and long non-coding RNA (lncRNA) have been demonstrated to participate in the progression of many cancers. Hepatocellular carcinoma (HCC) is one of the most common and aggressive malignant tumors worldwide, while the molecular mechanisms underlying HCC tumorigenesis are not completely clear. In this study, we showed that miR-92b was significantly upregulated in tumor tissue and plasma of HCC patients, and its expression level was highly correlated with gender and microvascular invasion. Functionally, miR-92b could promote cell proliferation and metastasis of HCC in vitro and in vivo. Mechanistic investigations suggested that Smad7, which exhibited an inverse relationship with miR-92b expression in HCC, was a direct target of miR-92b and could reverse its effects on HCC tumorigenesis. Furthermore, long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) and miR-92b could directly interact with and repress each other, and XIST could inhibit HCC cell proliferation and metastasis by targeting miR-92b. Taken together, our study not only revealed for the first time the importance of XIST/miR-92b/Smad7 signaling axis in HCC progression but also suggested the potential value of miR-92b as a biomarker in the clinical diagnosis and treatment of HCC.

HoxB7 PROMOTES GROWTH AND METASTASIS OF LUNG ADENOCARCINOMA CELLS THROUGH REGULATION OF THE TGF-ß/SMAD3 SIGNALING.

HoxB7 is involved in cell migration and metastasis in many malignant tumors. But, the role of HoxB7 in lung adenocarcinoma has not been elucidated. In the present study, we aimed to clarify the function of HoxB7 in the progression of lung adenocarcinoma. The protein expression of HoxB7 was examined by immunohistochemical assay in human lung adenocarcinoma tissues, and lentivirus-mediated HoxB7 shRNA (Lv-shHoxB7) was transfected into lung adenocarcinoma cells to evaluate cell proliferation and invasive potential indicated by MTT and Transwell assays. As a result, the protein expression level of HoxB7 was increased in lung adenocarcinoma tissues compared with the adjacent non-tumor tissues (56.25% vs 31.25%, P=0.014), and was positively correlated with the lymph node metastasis in patients with lung adenocarcinoma (P=0.036). Moreover, knockdown of HoxB7 decreased the proliferation and invasion of lung adenocarcinoma cells followed by decreased expression of TGF-ß/SMAD3, vascular endothelial growth factor A (VEGFA) and matrix metalloproteinase-2 (MMP-2). Taken together, our findings demonstrate that increased expression of HoxB7 is associated with tumor metastasis in patients with lung adenocarcinoma and HoxB7 may be implicated in promoting the development of lung adenocarcinoma through activation of the TGF-ß/SMAD3 signaling.