Local decorin delivery via hyaluronic acid microrods improves cardiac performance, ventricular remodeling after myocardial infarction.

Heart failure (HF) remains a global public health burden and often results following myocardial infarction (MI). Following injury, cardiac fibrosis forms in the myocardium which greatly hinders cellular function, survival, and recruitment, thus severely limits tissue regeneration. Here, we leverage biophysical microstructural cues made of hyaluronic acid (HA) loaded with the anti-fibrotic proteoglycan decorin to more robustly attenuate cardiac fibrosis after acute myocardial injury. Microrods showed decorin incorporation throughout the entirety of the hydrogel structures and exhibited first-order release kinetics in vitro. Intramyocardial injections of saline (n = 5), microrods (n = 7), decorin microrods (n = 10), and free decorin (n = 4) were performed in male rat models of ischemia-reperfusion MI to evaluate therapeutic effects on cardiac remodeling and function. Echocardiographic analysis demonstrated that rats treated with decorin microrods (5.21% ± 4.29%) exhibited significantly increased change in ejection fraction (EF) at 8 weeks post-MI compared to rats treated with saline (-4.18% ± 2.78%, p < 0.001) and free decorin (-3.42% ± 1.86%, p < 0.01). Trends in reduced end diastolic volume were also identified in decorin microrod-treated groups compared to those treated with saline, microrods, and free decorin, indicating favorable ventricular remodeling. Quantitative analysis of histology and immunofluorescence staining showed that treatment with decorin microrods reduced cardiac fibrosis (p < 0.05) and cardiomyocyte hypertrophy (p < 0.05) at 8 weeks post-MI compared to saline control. Together, this work aims to contribute important knowledge to guide rationally designed biomaterial development that may be used to successfully treat cardiovascular diseases.

Local delivery of decorin via hyaluronic acid microrods improves cardiac performance and ventricular remodeling after myocardial infarction.

Heart failure (HF) is a global public health burden and associated with significant morbidity and mortality. HF can result as a complication following myocardial infarction (MI), with cardiac fibrosis forming in the myocardium as a response to injury. The dense, avascular scar tissue that develops in the myocardium after injury following MI creates an inhospitable microenvironment that hinders cellular function, survival, and recruitment, thus severely limiting tissue regeneration. We have previously demonstrated the ability of hyaluronic acid (HA) polymer microrods to modulate fibroblast phenotype using discrete biophysical cues and to improve cardiac outcomes after implantation in rodent models of ischemia-reperfusion MI injury. Here, we developed a dual-pronged biochemical and biophysical therapeutic strategy leveraging bioactive microrods to more robustly attenuate cardiac fibrosis after acute myocardial injury. Incorporation of the anti-fibrotic proteoglycan decorin within microrods led to sustained release of decorin over one month in vitro and after implantation, resulted in marked improvement in cardiac function and ventricular remodeling, along with decreased fibrosis and cardiomyocyte hypertrophy. Together, this body of work aims to contribute important knowledge to help develop rationally designed engineered biomaterials that may be used to successfully treat cardiovascular diseases.

Engineering Phase Stability of Semimetallic MoS2 Monolayers for Sustainable Electrocatalytic Hydrogen Production.

1T'-phase MoS2 possesses excellent electrocatalytic performance, but due to the instability of the thermodynamic metastable phase, its actual electrocatalytic effect is seriously limited. Here, we report a wet-chemical synthesis strategy for constructing rGO/1T'-MoS2/CeO2 heterostructures to improve the phase stability of metastable 1T' phase MoS2 monolayers. Importantly, the rGO/1T'-MoS2/CeO2 heterostructure exhibits excellent electrocatalytic hydrogen evolution reaction (HER) performance, which is much better than the 1T'-MoS2 monolayers. The synergistic effects between CeO2 nanoparticles (NPs) and 1T'-MoS2 monolayers were systematically investigated. 1T'-MoS2 monolayers combined with the cocatalyst of CeO2 NPs can produce lattice strain and distortion on 1T'-MoS2 monolayers, which can tune the energy band structure, charge transfer, and energy barriers of hydrogen atom adsorption (ΔEH), leading to promotion of the phase activity and stability of 1T'-MoS2 monolayers for hydrogen production. Our work offers a feasible method for the preparation of efficient HER electrocatalysts based on the engineering phase stability of metastable materials.

A quantitative detection of mung bean in chestnut paste using duplex digital PCR.

Highly manufacturing process of chestnut paste leaves a considerable space for Economically Motivated Adulteration (EMA) with cheaper ingredients such as mung bean. In this paper a novel quantitative detection of mung bean in chestnut paste using duplex digital PCR was reported. Two sets of primers and probes were designed according to mung bean and chestnut specific genomic genes suitable for duplex droplet digital PCR (ddPCR) and duplex chip digital PCR (cdPCR) to set up a mass ratio quantitative detection method for mung bean, a common alternative plant-derived ingredient in chestnut paste products. The manufacturing process of chestnut paste products was considered to establish the linear relationship formula between mass ratio and gene copy number (CN) ratio of the two ingredients. The limits of quantification for gene CN concentrations (LOQcopy) of mung bean and chestnut were both 6 copies/µL, at the same time a mass ratio of mung bean in chestnut paste range from 5% to 80% was able to be quantified accurately to provide technical support for the identification of fraudulent substitution or adventitious contamination.

Cumulative Incidence and Risk Factors of Permanent Stoma After Intersphincteric Resection for Ultralow Rectal Cancer.

BACKGROUND: A permanent stoma is an unintended consequence that cannot be avoided completely after intersphincteric resection for ultralow rectal cancer. Unfortunately, its incidence and risk factors have been poorly defined. OBJECTIVE: The objective was to determine the cumulative incidence and risk factors of permanent stoma after intersphincteric resection for ultralow rectal cancer. DESIGN: This study was a retrospective analysis of prospectively collected data. SETTINGS: This study was conducted at a colorectal surgery referral center. PATIENTS: A total of 185 consecutive patients who underwent intersphincteric resection with diverting ileostomy from 2011 to 2019 were included. MAIN OUTCOME MEASURES: The primary outcome was the incidence of and risk factors for the permanent stoma. The secondary outcome included differences in stoma formation between patients with partial, subtotal, and total intersphincteric resection. RESULTS: After a median follow-up of 40 months (range, 6-107 months), 26 of 185 patients eventually required a permanent stoma, accounting for a 5-year cumulative incidence of 17.4%. The causes of permanent stoma were anastomotic morbidity (46.2%, 12/26), local recurrence (19.2%, 5/26), distant metastasis (19.2%, 5/26), fecal incontinence (3.8%, 1/26), perioperative mortality (3.8%, 1/26), patients' refusal (3.8%, 1/26), and poor general condition (3.8%, 1/26). Although the incidence of permanent stoma was significantly different between the intersphincteric resection groups (partial vs subtotal vs total: 8.3% vs 20% vs 25.8%, p = 0.02), it was not an independent predictor of stoma formation. Multivariate analysis demonstrated that anastomotic leakage (OR = 5.29; p = 0.001) and anastomotic stricture (OR = 5.13; p = 0.002) were independently predictive of permanent stoma. LIMITATIONS: This study was limited by its retrospective nature and single-center data. CONCLUSIONS: The 5-year cumulative incidence of permanent stoma was 17.4%. Anastomotic complications were identified as risk factors. Patients should be informed of the risks and benefits when contemplating the ultimate sphincter-sparing surgery. It might be preferable to decrease the probability of permanent stoma by further minimizing anastomotic complications. See Video Abstract at http://links.lww.com/DCR/B704. INCIDENCIA ACUMULADA Y FACTORES DE RIESGO DE ESTOMA PERMANENTE DESPUS DE UNA RESECCIN INTERESFNTRICA EN CNCER RECTAL ULTRA BAJO: ANTECEDENTES:La necesidad de efectuar un estoma permanente es la consecuencia no intencional e inevitable por completo después de una resección interesfintérica en presencia de un cáncer rectal ultra bajo. Desafortunadamente, la incidencia y los factores de riesgo se han definido en una forma limitada.OBJETIVO:El objetivo fue determinar la incidencia acumulada y los factores de riesgo para la necesidad de efectuar un estoma permanente después de la resección intersfintérica de un cáncer rectal ultra bajo.DISEÑO:El presente estudio es un análisis retrospectivo de la información obtenida.ESCENARIO:Centro de referencia de cirugía colo-rectal.PACIENTES:Se incluyeron un total de 185 pacientes consecutivos que se sometieron a resección intersfintérica de un cáncer rectal ultra bajo con ileostomía de derivación de 2011 a 2019.MEDICION DE RESULTADOS:El resultado principal fue la identificación de la incidencia y los factores de riesgo para la presencia de un estoma permanente. En forma secundaria se describieron los resultados de las diferentes técnicas de la formación de un estoma entre los pacientes con resección interesfintérica parcial, subtotal o total.RESULTADOS:Posterior a una media de seguimiento de cuarenta meses (rango de 6 a 107), 26 de 185 pacientes requirieron en forma eventual un estoma permanente, lo que equivale a una incidencia acumulada a cinco años de 17.4 %. Las causas para dejar un estoma permanente fueron morbilidad de la anastomosis (46.2%, 12/26), recurrencia local (19.2%, 5/26), metástasis a distancia (19.2%, 5/26), incontinencia fecal (3.8%, 1/26), mortalidad perioperatoria (3.8%, 1/26), rechazo del paciente (3.8%, 1/26), y malas condiciones generales (3.8%, 1/26). Aunque la incidencia de un estoma permanente fue significativamente diferente entre los grupos de resección interesfintérica (parcial vs subtotal vs total: 8.3% vs 20% vs 25.8%, p = 0.02), no se consideró un factor predictor independiente para la formación de estoma. En el análisis multivariado se demostró que la fuga anatomótica (OR = 5.29; p = 0.001) y la estenosis anastomótica (OR = 5.13; p = 0.002) fueron factores independientes para predecir la necesidad de un estoma permanente.LIMITACIONES:La naturaleza retrospectiva del estudio y la información proveniente de un solo centro.CONCLUSIONES:La incidencia acumulada a cinco años de estoma permantente fue de 17.4%. Se consideran a las complicaciones anastomóticas como factores de riesgo. Los pacientes deberán ser informados de los riesgos y beneficios cuando se considere la posibilidad de efectuar una cirugía preservadora de esfínteres finalmente. Puede ser preferible disminuir la probabilidad de dejar un estoma permanente tratando de minimizar la posibilidad de complicaciones de la anastomosis. Consulte Video Resumen en http://links.lww.com/DCR/B704.

A universal quantification of transgenic soybean event DAS-68416-4 using duplex digital PCR.

BACKGROUND: As labeling thresholds and low level presence thresholds of genetically modified (GM) components are implemented in more and more countries and regions, the demands for accurate quantification are increasing rapidly. At the same time, digital polymerase chain reaction (PCR) showed considerable benefits compared with former real-time fluorescence PCR in GM component quantification. RESULTS: A universal quantification method using duplex digital PCR was established for detection of transgenic soybean event DAS-68416-4. The absolute limits of quantification (LOQs) of DAS-68416-4 event-specific gene and lectin reference gene were 0.61 copies µL-1 and 4.6 copies µL-1 respectively in droplet digital PCR, while 0.522 copies µL-1 and 5.192 copies µL-1 in chip digital PCR. The relative LOQs of DAS-68416-4 percentage content was 0.1% in both two digital PCR systems. CONCLUSION: Gene copy ratio is the universal means of expression internationally used in transgenic component contents. Digital polymerase chain reaction (PCR) executes absolute quantification on specific genes, thus is considered to be suitable for detection of transgenic component contents. It was proved in this research on transgenic soybean event DAS-68416-4. Results indicated perfect satisfaction for transgenic component quantification needs in various technical performances of duplex digital PCR including repeatability, quantitative linear relationship and relative limits of quantification. © 2020 Society of Chemical Industry.

Mass ratio quantitative detection for kidney bean in lotus seed paste using duplex droplet digital PCR and chip digital PCR.

Two "mass ratio-DNA copy concentration ratio" formulas were established respectively on droplet digital PCR (ddPCR) and chip-based digital PCR (cdPCR) to determine the mass ratio of kidney bean, a common alternative plant-derived ingredient in lotus seed paste. The limit of detection for DNA copy concentration of kidney bean and lotus seed was 6 copies/µL. Quantitative detection range was set from 5 to 80%, and the limit of quantification for mass ratio of kidney bean in lotus seed paste was defined as 5%. Results of 6 simulated samples and 16 prepackaged pastes in this work offer compelling evidence that an innovative scheme for quantitative detection of kidney bean in lotus seed paste was available, and provide technical support for the identification of suspicious ingredients from fraudulent substitution or adventitious contamination. Graphical abstract Two "mass ratio-DNA copy concentration ratio" formulas were established respectively on droplet digital PCR (ddPCR) and chip digital PCR (cdPCR) to determine the mass ratio of kidney bean in adulterated lotus seed paste. It was the first time to quantify adulterate food by directly converting DNA copy concentration ratio obtained from digital PCR to mass ratio, which could provide strong technical support for quantitative detection of adulterated food.

Injectable Drug-Releasing Microporous Annealed Particle Scaffolds for Treating Myocardial Infarction.

Intramyocardial injection of hydrogels offers great potential for treating myocardial infarction (MI) in a minimally invasive manner. However, traditional bulk hydrogels generally lack microporous structures to support rapid tissue ingrowth and biochemical signals to prevent fibrotic remodeling toward heart failure. To address such challenges, a novel drug-releasing microporous annealed particle (drugMAP) system is developed by encapsulating hydrophobic drug-loaded nanoparticles into microgel building blocks via microfluidic manufacturing. By modulating nanoparticle hydrophilicity and pregel solution viscosity, drugMAP building blocks are generated with consistent and homogeneous encapsulation of nanoparticles. In addition, the complementary effects of forskolin (F) and Repsox (R) on the functional modulations of cardiomyocytes, fibroblasts, and endothelial cells in vitro are demonstrated. After that, both hydrophobic drugs (F and R) are loaded into drugMAP to generate FR/drugMAP for MI therapy in a rat model. The intramyocardial injection of MAP gel improves left ventricular functions, which are further enhanced by FR/drugMAP treatment with increased angiogenesis and reduced fibrosis and inflammatory response. This drugMAP platform represents a new generation of microgel particles for MI therapy and will have broad applications in regenerative medicine and disease therapy.

Apoptosis and injuries of heavy ion beam and x-ray radiation on malignant melanoma cell.

This study aims to investigate the influence of high linear energy transfer (LET) heavy ion (12C6+) and low LET X-ray radiation on apoptosis and related proteins of malignant melanoma on tumor-bearing mice under the same physical dosage. C57BL/6 J mice were burdened by tumors and randomized into three groups. These mice received heavy ion (12C6+) and X-ray radiation under the same physical dosage, respectively; their weight and tumor volumes were measured every three days post-radiation. After 30 days, these mice were sacrificed. Then, median survival time was calculated and tumors on mice were proliferated. In addition, immunohistochemistry was carried out for apoptosis-related proteins to reflect the expression level. After tumor-bearing mice were radiated to heavy ion, median survival time improved and tumor volume significantly decreased in conjunction with the upregulated expression of pro-apoptosis factors, Bax and cytochrome C, and the downregulated expression of apoptosis-profilin (Bcl-2, Survivin) and proliferation-related proteins (proliferating cell nuclear antigen). The results indicated that radiation can promote the apoptosis of malignant melanoma cells and inhibit their proliferation. This case was more suitable for heavy ion (12C6+). High LET heavy ion (12C6+) radiation could significantly improve the killing ability for malignant melanoma cells by inducing apoptosis in tumor cells and inhibiting their proliferation. These results demonstrated that heavy ion (12C6+) presented special advantages in terms of treating malignant melanoma. Impact statement Malignant melanoma is a malignant skin tumor derived from melanin cells, which has a high malignant degree and high fatality rate. In this study, proliferating cell nuclear antigen (PCNA) can induce the apoptosis of malignant melanoma cells and inhibit its proliferation, and its induction effect on apoptosis is significantly higher than low LET X-ray; hence, it is expected to overcome its lower sensitivity to radiation. This study can provide theoretical basis for clinical trials, in which malignant melanoma is treated by heavy ion (12C6+), in order to accurately determine the clinical efficacy of heavy ion therapy. Clinical applications has revealed that local tumor control rate is high when heavy ion is used to treat malignant melanoma, indicating that heavy ion is an important direction in treating melanoma in the future.

In vivo comparison of tantalum, tungsten, and bismuth enteric contrast agents to complement intravenous iodine for double-contrast dual-energy CT of the bowel.

To assess the ability of dual-energy CT (DECT) to separate intravenous contrast of bowel wall from intraluminal contrast, we scanned 16 rabbits on a clinical DECT scanner: n = 3 using only iodinated intravenous contrast, and n = 13 double-contrast enhanced scans using iodinated intravenous contrast and experimental enteric non-iodinated contrast agents in the bowel lumen (five bismuth, four tungsten, and four tantalum based). Representative image pairs from conventional CT images and DECT iodine density maps of small bowel (116 pairs from 232 images) were viewed by four abdominal imaging attending radiologists to independently score each comparison pair on a visual analog scale (-100 to +100%) for (1) preference in small bowel wall visualization and (2) preference in completeness of intraluminal enteric contrast subtraction. Median small bowel wall visualization was scored 39 and 42 percentage points (95% CI 30-44% and 36-45%, both p < 0.001) higher for double-contrast DECT than for conventional CT with enteric tungsten and tantalum contrast, respectively. Median small bowel wall visualization for double-contrast DECT was scored 29 and 35 percentage points (95% CI 20-35% and 33-39%, both p < 0.001) higher with enteric tungsten and tantalum, respectively, than with bismuth contrast. Median completeness of intraluminal enteric contrast subtraction in double-contrast DECT iodine density maps was scored 28 and 29 percentage points (95% CI 15-31% and 28-33%, both p < 0.001) higher with enteric tungsten and tantalum, respectively, than with bismuth contrast. Results suggest that in vivo double-contrast DECT with iodinated intravenous and either tantalum- or tungsten-based enteric contrast provides better visualization of small bowel than conventional CT. Copyright © 2016 John Wiley & Sons, Ltd.

Stimuli-induced organ-specific injury enhancement of organotropic metastasis in a spatiotemporal regulation.

The relationship between inflammation and tumorigenesis has been established. Recently, inflammation is also reported to be a drive force for cancer metastasis. Further evidences show that various stimuli directly induced-injury in a specific organ can also promote metastasis in this organ, which include epidemiological reports, clinical series and experimental studies. Each type of cancer has preferential sites for metastasis, which is also due to inflammatory factors that are released by primary cancer to act on these sites and indirectly induce injuries on them. Host factors such as stress,fever can also influence distant metastasis in a specific site through stimulation of immune and inflammatory effects. The five aspects support an idea that specific-organ injury directly induced by various stimuli or indirectly induced by primary tumor or host factors activation of proinflammatory modulators can promote metastasis in this organ through a spatiotemporal regulation, which has important implications for personalized prediction, prevention and management of cancer metastasis.

Biological resonance for cancer metastasis, a new hypothesis based on comparisons between primary cancers and metastases.

Many hypotheses have been proposed to try to explain cancer metastasis. However, they seem to be contradictory and have some limitations. Comparisons of primary tumors and matched metastases provide new insight into metastasis. The results show high concordances and minor differences at multiple scales from organic level to molecular level. The concordances reflect the commonality between primary cancer and metastasis, and also mean that metastatic cancer cells derived from primary cancer are quite conservative in distant sites. The differences reflect variation that cancer cells must acquire new traits to adapt to foreign milieu during the course of evolving into a new tumor in second organs. These comparisons also provided new information on understanding mechanism of vascular metastasis, organ-specific metastasis, and tumor dormancy. The collective results suggest a new hypothesis, biological resonance (bio-resonance) model. The hypothesis has two aspects. One is that primary cancer and matched metastasis have a common progenitor. The other is that both ancestors of primary cancer cells and metastatic cancer cells are under similar microenvironments and receive similar or same signals. When their interactions reach a status similar to primary cancer, metastasis will occur. Compared with previous hypotheses, the bio-resonance hypothesis seems to be more applicable for cancer metastasis to explain how, when and where metastasis occurs. Thus, it has important implications for individual prediction, prevention and treatment of cancer metastasis.

A comparison on expression of selected biomarkers between primary lung cancers and matched metastases.

Many biomarkers have been identified to be new targeted drugs for lung cancer treatment. Their clinical outcomes are determined by their status mainly evaluated from primary cancer tissues. However, metastasis is the leading cause of death in cancer patients. It is unclear whether their status in primary cancers is similar to that in corresponding metastases. Therefore, we aimed to evaluate similarities or differences for the selected biomarker expression between primary lung cancers and matched metastases and to provide evidence for further using these targets in metastatic tumors from lung cancer. Eleven patients who had received resection of paired tissues of primary lung cancers and matched metastases were collected. The protein expression of VEGF, HIF-1α, Met, P53, TGF-ß1, Cox-2 and TNF-α between paired tumors was detected by immunohistochemistry. The results showed that there was no statistical significance between primary cancers and matched metastases for the expressions of the selected biomarkers. The p values were more than 0.05. The major concordance of the selected biomarkers existed between paired primary and metastatic tumors. However, there were still minor differences. Differences in metastases compared with primary tumors were observed in respective two cases for VEGF, HIF-1α and Met, respective one case for TGF-ß1, COX2 and TNFα and three cases for P53. In conclusion, there were major concordance and minor difference for each biomarker between primary lung tumors and corresponding metastases, which may have important implications for the understanding of current metastasis models and treatment of advanced lung cancers.

The effect of a peptide-modified thermo-reversible methylcellulose on wound healing and LV function in a chronic myocardial infarction rodent model.

Myocardial infarction is the main contributor to heart failure. In this study we examined whether modification of a thermo-reversible cellulose-based polymer with extracellular-matrix derived functional groups could promote wound healing and improve cardiac function in a chronic rodent model of ischemic cardiomyopathy. To beneficially influence the microenvironment of the injured myocardium, we conjugated either the RGD peptide or the HepIII peptide to the polymer. In vitro cell adhesion studies showed that the peptide-modified polymer promoted cell attachment to the polymer surface. Injection of the thermo-reversible polymer into the aneurismal infarct region of the left ventricle showed that the peptide-modified polymer exhibited significantly improved left ventricular function, increased angiogenesis, decreased infarct size, and an increase in cardiomyocytes within the infarct region at 5 weeks post-treatment (P < 0.05). The results of this study demonstrate that a peptide-modified thermo-reversible polymer has the capability to alter left ventricular (LV) geometry, increase LV function, and promote myocardial regeneration in a chronic model of ischemic cardiomyopathy.

Extravasated contrast material in penetrating abdominopelvic trauma: dual-contrast dual-energy CT for improved diagnosis--preliminary results in an animal model.

PURPOSE: To compare the diagnostic performance of dual-energy (DE) computed tomography (CT) with two simultaneously administered contrast agents (hereafter, dual contrast) with that of conventional CT in the evaluation of the presence and source of extravasation in penetrating abdominopelvic trauma. MATERIALS AND METHODS: Institutional animal care and use committee approval was obtained, and the study was performed in accordance with National Institutes of Health guidelines for the care and use of laboratory animals. Five rabbits with bowel trauma, vascular penetrating trauma, or both were imaged with simultaneous iodinated intravenous and bismuth subsalicylate enteric contrast material at DE CT. Four attending radiologists and six radiology residents without prior DE CT experience each evaluated 10 extraluminal collections to identify the vascular and/or enteric origin of extravasation and assess their level of diagnostic confidence, first with virtual monochromatic images simulating conventional CT and then with DE CT material decomposition attenuation maps. RESULTS: Overall accuracy of identification of source of extravasation increased from 78% with conventional CT to 92% with DE CT (157 of 200 diagnoses vs 184 of 200 diagnoses, respectively; P < .001). Nine radiologists were more accurate with DE CT; one had no change. Mean confidence increased from 67% to 81% with DE CT (P < .001). CONCLUSION: In a rabbit abdominopelvic trauma model, dual-contrast DE CT significantly increased accuracy and confidence in the diagnosis of vascular versus enteric extravasated contrast material.

Role of the nervous system in cancer metastasis.

The notion that tumors lack innervation was proposed several years ago. However, nerve fibers are irregulatedly found in some tumor tissues. Their terminals interaction with cancer cells are considered to be neuro-neoplastic synapses. Moreover, neural-related factors, which are important players in the development and activity of the nervous system, have been found in cancer cells. Thus, they establish a direct connection between the nervous system and tumor cells. They modulate the process of metastasis, including degradation of base membranes, cancer cell invasion, migration, extravasation and colonization. Peripheral nerve invasion provides another pathway for the spread of cancer cells when blood and lymphatic metastases are absent, which is based on the interactions between the microenvironments of nerve fibers and tumor cells. The nervous system also modulates angiogenesis, the tumor microenvironment, bone marrow, immune functions and inflammatory pathways to influence metastases. Denervation of the tumor has been reported to enhance cancer metastasis. Stress, social isolation and other emotional factors may increase distant metastasis through releasing hormones from the brain, the hypothalamic-pituitary-adrenal axis and autonomic nervous system. Disruption of circadian rhythms will also promote cancer metastasis through direct and indirect actions of the nervous system. Therefore, the nervous system plays an important role in cancer metastasis.

Expression of HGF and Met in human tissues of colorectal cancers: biological and clinical implications for synchronous liver metastasis.

BACKGROUND AND AIMS: Synchronous liver metastasis (SLM) remains a significant problem in newly diagnosed colorectal cancer (CRC). The system of hepatocyte growth factor (HGF) and Met plays an important role in cancer invasion and metastasis and is being developed to be targeted drugs. We aimed to investigate the role of HGF/Met in SLM based on a case-matched study and comparison between primary tumors and matched metastases. METHODS: A group of 30 patients with SLM and other two groups of patients without SLM in a hospital database were collected. They were matched into according to clinicopathological factors. 81 patients were included in the study. Their tissues of primary colorectal cancers, lymph nodes and liver metastases were collected to detect HGF and Met expression by immunohistochemistry and RT-PCR. RESULTS: Expression of HGF and Met at the protein level and the RNA level in primary CRCs with SLM were significantly higher than that in primary colorectal carcinomas without liver metastases (all P value<0.05). Their expression was only related to SLM when concurrent with regional lymph node metastasis (all P value<0.05) but had little influence on SLM without involvement of lymph node metastasis (all P value>0.05). Comparison their expression between primary tumors and matched metastases, major concordance and minor difference existed. CONCLUSIONS: HGF and Met may exert functions in the development of SLM when concurrent with lymph node metastases but had little influence on SLM without lymph node metastasis, further indicating their roles and potential values for a subtype of colorectal cancer metastasis. Major concordance and minor difference exist between primary tumors and matched metastases, which further provides evidence for evaluating the response to their inhibitors based on primary tumors or metastases.

Hepatic fibrosis: evaluation with semiquantitative contrast-enhanced CT.

PURPOSE: To evaluate the feasibility of using contrast material-enhanced computed tomographic (CT) measurements of hepatic fractional extracellular space (fECS) and macromolecular contrast material (MMCM) uptake to measure severity of liver fibrosis. MATERIALS AND METHODS: All procedures were approved by and executed in accordance with University of California, San Francisco, institutional animal care and use committee regulations. Twenty-one rats that received intragastric CCl(4) for 0-12 weeks were imaged with respiratory-gated micro-CT by using both a conventional contrast material and a novel iodinated MMCM. Histopathologic hepatic fibrosis was graded qualitatively by using the Ishak fibrosis score and quantitatively by using morphometry of the fibrosis area. Hepatic fECS and MMCM uptake were calculated for each examination and correlated with histopathologic findings by using uni- and multivariate linear regressions. RESULTS: Ishak fibrosis scores ranged from a baseline of 0 in untreated animals to a maximum of 5. Histopathologic liver fibrosis area increased from 0.46% to 3.5% over the same interval. Strong correlations were seen between conventional contrast-enhanced CT measurements of fECS and both the Ishak fibrosis scores (R(2) = 0.751, P < .001) and the fibrosis area (R(2) = 0.801, P < .001). Strong negative correlations were observed between uptake of MMCM in the liver and Ishak fibrosis scores (R(2) = 0.827, P < .001), as well as between uptake of MMCM in the liver and fibrosis area (R(2) = 0.643, P = .001). Multivariate linear regression analysis showed a trend toward independence for fECS and MMCM uptake in the prediction of Ishak fibrosis scores, with an R(2) value of 0.86 (P = .081 and P = .033, respectively). CONCLUSION: Contrast-enhanced CT measurements of fECS and MMCM uptake are individually capable of being used to estimate the degree of early hepatic fibrosis in a rat model. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12112452/-/DC1.

Expression of efflux pump gene lde in ciprofloxacin-resistant foodborne isolates of Listeria monocytogenes.

The expression of efflux pump gene lde in ciprofloxacin resistant (Cip(R) ) and susceptible strains of Listeria monocytogenes collected from retail food samples was investigated. For two Cip(R) strains, the MICs of ciprofloxacin decreased four- to eightfold in the presence of reserpine; however, no significant alterations were observed with naturally sensitive isolates. Overexpression of the lde gene induced by ciprofloxacin was observed in two resistant isolates. The present findings indicate that expression of lde and the MICs of ciprofloxacin are well correlated with the presence and absence of reserpine, suggesting that Lde might be involved in ciprofloxacin resistance of L. monocytogenes.

In vivo differentiation of complementary contrast media at dual-energy CT.

PURPOSE: To evaluate the feasibility of using a commercially available clinical dual-energy computed tomographic (CT) scanner to differentiate the in vivo enhancement due to two simultaneously administered contrast media with complementary x-ray attenuation ratios. MATERIALS AND METHODS: Approval from the institutional animal care and use committee was obtained, and National Institutes of Health guidelines for the care and use of laboratory animals were observed. Dual-energy CT was performed in a set of iodine and tungsten solution phantoms and in a rabbit in which iodinated intravenous and bismuth subsalicylate oral contrast media were administered. In addition, a second rabbit was studied after intravenous administration of iodinated and tungsten cluster contrast media. Images were processed to produce virtual monochromatic images that simulated the appearance of conventional single-energy scans, as well as material decomposition images that separate the attenuation due to each contrast medium. RESULTS: Clear separation of each of the contrast media pairs was seen in the phantom and in both in vivo animal models. Separation of bowel lumen from vascular contrast medium allowed visualization of bowel wall enhancement that was obscured by intraluminal bowel contrast medium on conventional CT scans. Separation of two vascular contrast media in different vascular phases enabled acquisition of a perfectly coregistered CT angiogram and venous phase-enhanced CT scan simultaneously in a single examination. CONCLUSION: Commercially available clinical dual-energy CT scanners can help differentiate the enhancement of selected pairs of complementary contrast media in vivo.