Citrus oil gland and cuticular wax inspired multifunctional gelatin film of OSA-starch nanoparticles-based nanoemulsions for preserving perishable fruit.

Inspired by the citrus oil gland and cuticular wax, a multifunctional material that stably and continuously released the carvacrol and provided physical defenses was developed to address issues of fresh-cut fruits to microbial infestation and moisture loss. The results confirmed that low molecular weight and loose structure of starch nanoparticles prepared by the ultrasound-assisted Fenton system were preferable for octenyl succinic anhydride modification compared to native starch, achieving a higher degree of substitution (increased by 18.59 %), utilizing in preparing nanoemulsions (NEs) for encapsulating carvacrol (at 5 % level: 81.58 %). Furthermore, the NEs-based gelatin (G) film improved with surface hydrophobic modification by myristic acid (MA) successfully replicated the citrus oil gland and cuticular wax, providing superior antioxidant (enhanced by 3-4 times) and antimicrobial properties (95.99 % and 84.97 % against Staphylococcus aureus and Escherichia coli respectively), as well as the exceptional UV shielding (nearly 0 transmittance in the UV region), mechanical (72 % increase in tensile strength), and hydrophobic (WCA 133.63°). Moreover, the 5%NE-G@MA film inhibited foodborne microbial growth (reduced by 50 %) and water loss (controlled below 15 %), extending the shelf life of fresh-cut navel orange and kiwi. Thus, the multifunctional film was a potential shield for preserving perishable fresh-cut products.

Grafting chlorogenic acid enhanced the antioxidant activity of curdlan oligosaccharides and modulated gut microbiota.

In this study, the effects of grafting chlorogenic acid (CA) on the antioxidant and probiotic activities of curdlan oligosaccharides (CDOS) were investigated. CDOS with degrees of polymerization of 3-6 was first obtained by degradation of curdlan with hydrogen peroxide and then grafted with CA using a free radical-mediated method under an ultrasonication-assisted Fenton system. The thermal stability and antioxidant ability of CDOS were enhanced after grafting with CA. In vitro fermentation, supplementation of CDOS-CA stimulated the proliferation of Prevotella and Faecalibacterium while inhibiting the growth of harmful microbiota. Notably, the concentration of total short-chain fatty acids and the relative abundance of beneficial bacteria markedly increased after fermentation of CDOS-CA, indicating that CA grafting could improve the probiotic activity of CDOS. Overall, the covalent binding of CDOS and CA could enhance the antioxidant and probiotic activities of CDOS, suggesting potential improvements in gastrointestinal and colonic health.

Diagnostic performance of artificial intelligence-based computer-aided diagnosis system in longitudinal and transverse ultrasonic views for differentiating thyroid nodules.

Objective: To evaluate the diagnostic performance of different ultrasound sections of thyroid nodule (TN) using computer-aided diagnosis system based on artificial intelligence (AI-CADS) in predicting thyroid malignancy. Materials and methods: This is a retrospective study. From January 2019 to July 2019, patients with preoperative thyroid ultrasound data and postoperative pathological results were enrolled, which were divided into two groups: lower risk group (ACR TI-RADS 1, 2 and 3) and higher risk group (ACR TI-RADS 4 and 5). The malignant risk scores (MRS) of TNs were obtained from longitudinal and transverse sections using AI-CADS. The diagnostic performance of AI-CADS and the consistency of each US characteristic were evaluated between these sections. The receiver operating characteristic (ROC) curve and the Cohen κ-statistic were performed. Results: A total of 203 patients (45.61 ± 11.59 years, 163 female) with 221 TNs were enrolled. The area under the ROC curve (AUC) of criterion 3 [0.86 (95%CI: 0.80~0.91)] was lower than criterion 1 [0.94 (95%CI: 0.90~ 0.99)], 2 [0.93 (95%CI: 0.89~0.97)] and 4 [0.94 (95%CI: 0.90, 0.99)] significantly (P<0.001, P=0.01, P<0.001, respectively). In the higher risk group, the MRS of transverse section was higher than longitudinal section (P<0.001), and the agreement of extrathyroidal extension and shape was moderate and fair (κ =0.48, 0.31 respectively). The diagnostic agreement of other ultrasonic features was substantial or almost perfect (κ >0.60). Conclusion: The diagnostic performance of computer-aided diagnosis system based on artificial intelligence (AI-CADS) in longitudinal and transverse ultrasonic views for differentiating thyroid nodules (TN) was different, which was higher in the transverse section. It was more dependent on the section for the AI-CADS diagnosis of suspected malignant TNs.

Preoperative Value of Contrast-Enhanced Ultrasound in Totally Laparoscopic Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy for Liver Tumors: A Preliminary Study.

ABSTRACT: The clinical data of 15 cases that planned to receive totally laparoscopic associating liver partition and portal vein ligation for staged hepatectomy were retrospectively collected. Before the stage 1 operation, the size and number of the tumors in future liver remnant (FLR) and the presence of cancer embolus in the portal vein were assessed using contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CECT). Before the stage 2 operation, CEUS was performed to assess the presence of traffic blood flow between the diseased liver and FLR after round-the-liver ligation. Before the stage 1 operation, 5 cases with tumors in FLR were found by CEUS and 6 cases were found by CECT ( P > 0.05). Similarly, CEUS found 5 cases with cancer thrombus in portal vein, and CECT found 7 cases ( P = 0.500). The consistency between the 2 modalities was good (κ = 0.857, P < 0.05, κ = 0.727, P < 0.05, respectively). Before the stage 2 operation, CEUS confirmed that there were 7 cases without traffic blood flow between the diseased liver and FLR, and 3 cases with residual traffic blood flow. The daily growth rate of FLR in the group without traffic blood flow (mean rank = 7.00) was higher than that in the group with traffic blood flow (2.00) significantly ( P < 0.05). Contrast-enhanced ultrasound is a promising application in the preoperative evaluation of totally laparoscopic associating liver partition and portal vein ligation for staged hepatectomy.

Up-regulated SAMD9L modulated by TLR2 and HIF-1α as a promising biomarker in tuberculosis.

The aim of this study was to identify potential biomarkers of TB in blood and determine their function in Mtb-infected macrophages. First of all, WGCNA was used to analyse 9451 genes with significant changes in TB patients' whole blood. The 220 interferon-γ-related genes were identified, and then 30 key genes were screened using Cytoscape. Then, the AUC values of key genes were calculated to further narrow the gene range. Finally, we identified 9 genes from GSE19444. ROC analysis showed that SAMD9L, among 9 genes, had a high diagnostic value (AUC = 0.925) and a differential diagnostic value (AUC>0.865). To further narrow down the range of DEGs, the top 10 hub-connecting genes were screened from monocytes (GSE19443). Finally, we obtained 4 genes (SAMD9L, GBP1, GBP5 and STAT1) by intersections of genes from monocytes and whole blood. Among them, it was found that the function of SAMD9L was unknown after data review, so this paper studied this gene. Our results showed that SAMD9L is up-regulated and suppresses cell necrosis, and might be regulated by TLR2 and HIF-1α during Mtb infection. In addition, miR-181b-5p is significantly up-regulated in the peripheral blood plasma of tuberculosis patients, which has a high diagnostic value (AUC = 0.969).

Preoperative Serum Calcitonin Level and Ultrasonographic Characteristics Predict the Risk of Metastatic Medullary Thyroid Carcinoma: Functional Analysis of Calcitonin-Related Genes.

Background: Early cervical lymph node (LN) metastasis is an important cause of poor survival in patients with medullary thyroid cancer (MTC). This study evaluated whether the preoperative serum calcitonin level in combination with ultrasonographic features of MTC can be used to assess the LN status as well as predict the risk of metastasis in patients with MTC. Methods: We retrospectively analyzed the clinical data of 95 patients with MTC, and a nomogram model was constructed and validated. Using integrated database analysis of The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx), we mined pathways wherein CALCA is involved, identified calcitonin-related genes, and analyzed their functions. Results: Correlation analysis revealed a significant association between the infiltrating range, diameter, calcification, blood flow, the preoperative serum calcitonin level, and metastasis. The metastasis risk-prediction model showed great accuracy in determining the risk of metastasis in MTC (area under the curve of the receiver operating characteristic [ROC] curve: 0.979 [95% confidence interval 0.946-1.000]). Decision curve analysis (DCA) showed that the model has excellent clinical utilization potential. Significantly, CALCA, the mRNA for calcitonin, was highly expressed in thyroid cancer tissues and associated with the cytokine-cytokine receptor and neuroactive ligand-receptor interaction pathways as well as the cell-adhesion molecules. ROC curve indicated that the CNTFR, CD27, GDF6, and TSLP genes, which are related to the cytokine-cytokine receptor interaction pathway, could indicate the risk of metastasis in MTC. Conclusions: The preoperative serum calcitonin level, in combination with ultrasonographic features, can be used to predict the risk of metastasis in patients with MTC and constitute a noninvasive accurate method for preoperative diagnosis of MTC.

Effects of tanshinone combined with valsartan on hypertensive nephropathy and its influence on renal function and vascular endothelial function.

OBJECTIVE: To investigate the curative effects of tanshinone combined with valsartan on hypertensive nephropathy and its influence on renal and endothelial damage. METHODS: A total of 102 hypertensive nephropathy patients who were admitted to our hospital from October 2015 to November 2019 were recruited and divided into a monotherapy group (MG, n=54) and a combined group (CG, n=48), in accordance with the treatment methods. Based on routine treatment, patients in the CG received treatment of tanshinone combined with valsartan, while patients in the MG received treatment of valsartan only. The clinical efficacy, adverse reactions, blood pressure, renal function indexes, vascular endothelial injury indexes, levels of inflammatory cytokines and stress response indexes of the two groups were compared. RESULTS: After treatment, the effective rate in the CG was higher than that in the MG, and the levels of systolic blood pressure (SBP), diastolic blood pressure (DBP), serum creatinine (Scr), blood urea nitrogen (BUN) and microalbumin (mAlb) in the CG were lower than those in the MG (P < 0.05). After treatment, endothelin-1 (ET-1) and thromboxane B2 (TXB2) levels in the CG were lower than those in the MG, while nitric oxide (NO) level was higher than that in the MG (P < 0.05). No serious adverse reactions occurred in the two groups during treatment, with similar situations (P > 0.05). The serum levels of interleukin-6 (IL-6), C-reactive protein (CRP), tumor necrosis factor (TNF-α), malondialdehyde (MDA) and advanced oxidation protein products (AOPP) in the CG were lower than those in the MG after treatment, while the level of glutathione peroxidase (GSH-Px) was higher (P < 0.05). CONCLUSION: Tanshinone combined with valsartan can treat hypertensive nephropathy safely and effectively, and reduce renal and endothelial damage by reducing inflammation and oxidative stress.

The effects of ultrasound-guided radiofrequency ablation and laparoscopic hepatectomy in the treatment of small hepatocellular carcinoma: a retrospective analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is a commonly-seen cancer in the clinical setting. Laparoscopic hepatectomy (LH) and radiofrequency ablation (RFA) are used for the treatment of HCC, yet the effects and safety difference of LH and RFA for HCC treatment need further investigation. METHODS: This study was a retrospective study design. HCC patients treated with LH or RFA in our hospital were identified. All the patients underwent 2-year long follow-up. The characteristics and details of LH and RFA groups during hospitalization were collected and compared. The Kaplan-Meier method was used to calculate the cumulative survival, and the survival curve was drawn and compared. RESULTS: A total of 94 HCC patients were included. The duration of surgery, estimated intraoperative blood loss, pain score on the first day after surgery, time to get out of bed after operation, time to oral eating, aspartate transaminase (AST) on the second day after surgery, C-reactive protein (CRP) on the second day after surgery, total medical cost in RFA group were significantly less than that of LH group (all P<0.05). The incidence of abdominal infection and biliary fistula in RFA group were significantly less than that of LH group (all P<0.05), and there was no significant difference in the incidence of bleeding and pleural effusion between two groups (all P>0.05). The 2-year overall survival and recurrence-free survival of the two groups had no significant statistical difference (all P>0.05). CONCLUSIONS: RFA and LH have similar effects in the treatment of small HCC. And RFA has the advantages of less trauma, shorter operation duration, and quick postoperative recovery.

Changes in volatile compounds of fermented minced pepper during natural and inoculated fermentation process based on headspace-gas chromatography-ion mobility spectrometry.

Changes in volatile compounds of fermented minced pepper (FMP) during natural fermentation (NF) and inoculated fermentation (IF) process were analyzed by the headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS). A total of 53 volatile compounds were identified, including 12 esters, 17 aldehydes, 13 alcohols, four ketones, three furans, two acids, one pyrazine, and one ether. Generally, fermentation time played an important role in volatile compounds of FMP. It was found that most esters, aldehydes, and alcohols obviously decreased with the increase in fermentation time, including isoamyl hexanoate, methyl octanoate, gamma-butyrolactone, phenylacetaldehyde, methional, and E-2-hexenol. Only a few volatile compounds increased, especially for 2-methylbutanoic acid, 2-methylpropionic acid, linalool, ethanol, and ethyl acetate. However, no significant difference in volatile compounds was found between NF and IF samples at the same fermentation time. In addition, the fermentation process in all samples was well discriminated as three stages (0 days; 6 day; and 12, 18, and 24 days), and all volatile compounds were divided into two categories (increase and decrease) based on principal component analysis and heat map.

Identification of characteristic heroin metabolites in urine based on data-mining technology and multivariate statistics analysis combined with a targeted verification approach for distinguishing heroin abusers.

A common phenomenon shows that ingestion of opium poppy shell-containing drugs can result in a "false-positive" urinalysis test result for mandatory or workplace heroin abuse screening. Owing to the short detection window (8 h in urine) of the characteristic heroin metabolite 6-monoacetylmorphine (6-MAM) confirmation or exclusion of heroin abusers still presents major challenges for toxicologists. In this work, we developed an ultra-performance liquid chromatography-time-of-flight mass spectrometry method (UPLC-TOF-MS) with online data acquisition and multiple post-data-mining technologies combined with a multivariate statistical and batch validation analysis workflow to assess the characteristic urine metabolites of heroin abusers. Based on the proposed methods, 28 characteristic metabolites were structurally identified, and their fragmentation patterns and metabolite pathways were also summarized. Correlation analysis was used to investigate the internal relationship and similarities among the identified metabolites, and seven representative metabolites were selected as "Target-metabolites". Multi-batch urine of samples of heroin abusers were certified based on the UPLC-MS/MS method for further validation of the practicability of using this method for routine analysis. Overall, the target-metabolites can be utilized as assistant "biomarkers" in workplace or mandatory drug screenings. This approach encourages further studies on the development of the "false-positive" identification system.

[The value of thyroglobulin measurement in fine-needle aspiration for diagnosis of suspicious lymph nodes in patients with thyroid carcinoma after thyroidectomy].

OBJECTIVE: To investigate the value of thyroglobulin measurement in ultrasound guided fine-needle aspiration(FNA-Tg)for detecting neck node metastasis in patients with papillary thyroid carcinoma(PTC)after thyroidectomy. METHODS: A total of 128 suspicious metastatic lymph nodes in 112 patients were retrospectively analyzed. Postoperative pathologic results were taken as the gold standard. The values of FNA and FNA-Tg combined FNA in the diagnosis of metastatic lymph nodes were compared with different ultrasonic features. RESULTS: The sensitivity, specificity and accuracy of single FNA for the diagnosis of neck node metastasis were 67.5%, 98.0% and 79.7% respectively, and those of FNA-Tg combined FNA were 87.0%, 100.0% and 92.2% respectively. Compared with single FNA, the sensitivity and accuracy of FNA-Tg combined FNA were increased significantly(χ(2)=8.319, P=0.004; χ(2)=8.275, P=0.004). When the ultrasonographic characteristics met any one of five indicators for neck node metastasis, the sensitivity, specificity and accuracy of single FNA for the diagnosis of neck node metastasis were 38.1%, 95.7% and 68.2% respectively, and those of FNA-Tg combined FNA were 71.0%, 100.0% and 86.4% respectively. Compared with single FNA, the sensitivity and accuracy of FNA-Tg combined FNA were increased significantly(χ(2)=4.709, P=0.030; χ(2)=4.141, P=0.042). When the ultrasonographic characteristics met any two of five indicators for neck node metastasis, the sensitivity, specificity and accuracy of single FNA for the diagnosis of neck node metastasis were 55.0%, 100.0% and 73.5% respectively, and those of FNA-Tg combined FNA were 90.0%, 100.0% and 94.1% respectively. Compared with single FNA, the sensitivity and accuracy of FNA-Tg combined FNA were increased significantly(χ(2)=6.140, P=0.013; χ(2)=5.314, P=0.021). The ultrasonographic characteristics met any three, four or five of five indicators or did not meet any of the indicators, there was no significant difference in the value of the diagnosis of metastatic lymph nodes between single FNA and FNA-Tg combined FNA(P>0.05). CONCLUSIONS: The combination of FNA with FNA-Tg could be helpful in diagnosis of lymph node metastasis. When the suspicious lymph nodes had one or two ultrasound characteristics for neck node metastasis, FNA-Tg could raise the sensitivity and accuracy of FNA, and FNA-Tg could not significantly improve in the diagnosis of FNA when presenting with no or with more than 2 ultrasonographic features.

[Application value of contrast-enhanced ultrasonography for assessing the high-risk population of hepatic malignant tumor].

OBJECTIVE: To investigate the clinical value of contrast-enhanced ultrasonography (CEUS) in assessing the high-risk population of hepatic malignant tumor (HMT). METHODS: Three hundred patients with high-risk of HMT were enrolled and examined by CEUS. The clinical data of these patients were collected. A comparative analysis was performed to assess the ability of CEUS for detecting and characterizing lesions in the liver. Kappa test was used for assessing the intra-and inter-observer reliability of CEUS. RESULTS: In 87 enrolled patients with 119 malignant lesions detected by contrast-enhanced MRI, 112 lesions were detected by CEUS and 95 lesions were detected by unenhanced ultrasonography (US). The detection rate of CEUS for HMT was significant higher than that of US (94.1% vs. 79.8%; P < 0.01). More HMT lesions were detected by CEUS than by US in 17.2% patients. One hundred and seventy-seven patients with 215 lesions were confirmed by pathological diagnosis or long-time follow-up. There were 118 malignant and 97 benign lesions. The accuracy of CEUS for differential diagnosis of the liver lesions was 91.6% (197/215), significantly higher than that by US (59.1%, 127/215) (P < 0.01). CEUS improved the accuracy for 35.0% (62/177) patients. For 96 patients with 105 lesions detected for the first time, the agreement of diagnosis by CEUS was 92.4% (97/105). The reliability of CEUS was high (Kappainter = 0.866; Kappaintra = 0.934). CONCLUSIONS: CEUS improves the detection rate and diagnostic accuracy rate of the HMT high-risk population, with a high agreement for diagnosing the new lesions. CEUS may be considered as a first-line method to assess the high-risk population of HMT conveniently, accurately and reliably.

Inhibition of Bcl-2 sensitizes mitochondrial permeability transition pore (MPTP) opening in ischemia-damaged mitochondria.

BACKGROUND: Mitochondria are critical to cardiac injury during reperfusion as a result of damage sustained during ischemia, including the loss of bcl-2. We asked if bcl-2 depletion not only leads to selective permeation of the outer mitochondrial membrane (MOMP) favoring cytochrome c release and programmed cell death, but also favors opening of the mitochondrial permeability transition pore (MPTP). An increase in MPTP susceptibility would support a role for bcl-2 depletion mediated cell death in the calcium overload setting of early reperfusion via MPTP as well as later in reperfusion via MOMP as myocardial calcium content normalizes. METHODS: Calcium retention capacity (CRC) was used to reflect the sensitivity of the MPTP opening in isolated cardiac mitochondria. To study the relationship between bcl-2 inhibition and MPTP opening, mitochondria were incubated with a bcl-2 inhibitor (HA14-1) and CRC measured. The contribution of preserved bcl-2 content to MPTP opening following ischemia-reperfusion was explored using transgenic bcl-2 overexpressed mice. RESULTS: CRC was decreased in mitochondria following reperfusion compared to ischemia alone, indicating that reperfusion further sensitizes to MPTP opening. Incubation of ischemia-damaged mitochondria with increasing HA14-1concentrations increased calcium-stimulated MPTP opening, supporting that functional inhibition of bcl-2 during simulated reperfusion favors MPTP opening. Moreover, HA14-1 sensitivity was increased by ischemia compared to non-ischemic controls. Overexpression of bcl-2 attenuated MPTP opening in following ischemia-reperfusion. HA14-1 inhibition also increased the permeability of the outer membrane in the absence of exogenous calcium, indicating that bcl-2 inhibition favors MOMP when calcium is low. CONCLUSIONS: The depletion and functional inhibition of bcl-2 contributes to cardiac injury by increasing susceptibility to MPTP opening in high calcium environments and MOMP in the absence of calcium overload. Thus, ischemia-damaged mitochondria with decreased bcl-2 content are susceptible to MPTP opening in early reperfusion and MOMP later in reperfusion when cytosolic calcium has normalized.

Enhanced intensity on preoperative double contrast-enhanced sonography as a useful indicator of lymph node metastasis in patients with gastric cancer.

OBJECTIVES: The aim of this study was to investigate the predictive value of enhanced intensity on double contrast-enhanced sonography in assessing lymph node metastasis of gastric cancer. METHODS: A total of 357 patients with gastric cancer were enrolled in this study. Double contrast-enhanced sonography, in which an oral ultrasound contrast agent is combined with an intravenous contrast agent, was performed preoperatively, and the data were analyzed quantitatively. The predictive ability of enhanced intensity, a quantitative double contrast-enhanced sonographic measure, for lymph node metastasis was evaluated retrospectively. RESULTS: Compared to negative lymph node metastasis cases, the presence of thicker lesions, deeper invasion, poorer differentiation, and higher enhanced intensity were found in positive cases (P< .05). An enhanced intensity cutoff value of 16.91 dB was the best point for balancing the sensitivity and specificity (71.50% and 79.30%, respectively) for prediction of lymph node metastasis, with the highest Youden index of 0.508. The area under the receiver operating characteristic curve was 0.828 (P < .001; 95% confidence interval, 0.786-0.870). In cases in which the lesions were hyperenhanced (enhanced intensity >16.91 dB), the lesions were significantly thicker and had deeper invasion, poorer differentiation, and more positive metastasis findings compared to non-hyperenhanced cases (enhanced intensity ≤16.91 dB; P < .05). On logistic regression analysis, the enhanced intensity of primary tumors and the invasion depth were significantly associated with lymph node metastasis. CONCLUSIONS: Double contrast-enhanced sonography with quantitative analysis may be considered a novel alternative imaging modality for noninvasive preoperative evaluation of lymph node metastasis with good reliability.

[Sonographic features and diagnostic analysis of breast granulomatous diseases: a report of 32 cases].

OBJECTIVE: To evaluate the sonographic features of different pathological types of breast granulomatous diseases and analyze the feasibility of ultrasonic diagnosis. METHODS: A total of 32 patients with different pathological types of breast granulomatous diseases were recruited. Their clinical and sonographic findings were retrospectively reviewed. There were granulomatous mastitis (n = 12), breast xanthogranuloma (n = 5), lipogranuloma (n = 2), foreign body granuloma (n = 1) and nonspecific granulation hyperplasia (n = 12). RESULTS: Based on major sonographic appearances, they were divided into 4 patterns of tubular, mass, diffuse and cystic mass. In 12 patients with granulomatous mastitis and 12 patients with nonspecific granulation hyperplasia, the major sonographic appearance was of tubular pattern (n = 6, 5), followed by mass pattern (n = 4, 5) and diffuse pattern (n = 2, 2). Five patients with breast xanthogranuloma and 1 patient with foreign body granuloma all showed mass pattern. In 2 patients with lipogranuloma, one was of mass pattern and another cystic pattern. In patients with granulomatous mastitis and patients with nonspecific granulation hyperplasia, it showed a high diagnostic reliability of ultrasound. The ratio of inflammatory lesion as the first sonographic diagnosis was 10/12 and 8/12 respectively and ultrasonic BI-RADS 4b or above both only 1/12. However, the ratio of sonographic imaging in patients with xanthogranuloma and Lipogranuloma mimic breast cancer, in which ultrasonic score as breast imaging-reporting and data system (BI-RADS) 4b or above was 4/5 and 1/1 respectively. CONCLUSIONS: Ultrasound is valuable in evaluating the lesions in patients with granulomatous mastitis and nonspecific granulation hyperplasia. However a definite diagnosis is still dependent on histopathology.

Actinomycin D decreases Mcl-1 expression and acts synergistically with ABT-737 against small cell lung cancer cell lines.

PURPOSE: ABT-737, which blocks the function of Bcl-2 and Bcl-X(L) but not Mcl-1, has shown single-agent activity in preclinical models of small cell lung cancer (SCLC). Elevated expression of Mcl-1 induces resistance to ABT-737 in SCLC. Based on the short half-life of Mcl-1 mRNA and protein, we hypothesized that the actinomycin D could reverse Mcl-1-induced resistance to ABT-737. EXPERIMENTAL DESIGN: The dose-response of multiple SCLC cell lines to actinomycin D in the absence and presence of ABT-737 was followed by the assessment of Bcl-2 family expression and poly ADP ribose polymerase cleavage by Western blot, viability by tetrazolium dye reduction and clonogenic assay, and cell cycle kinetics by flow cytometry. RESULTS: Actinomycin D decreased Mcl-1 expression and resulted in a cell line-dependent increase in Noxa expression. Clinically relevant concentrations of actinomycin D from 0.4 to 4 ng/mL showed single-agent activity across a panel of SCLC cell lines. When combined with low micromolar doses of ABT-737, near complete loss of viability was seen with synergistic combination indices of 0.5 to 0.7. Exposure to 4 ng/mL actinomycin was only required for the first 24 hours of the combined incubation, mimicking a clinically achievable area under the curve, but the presence of ABT-737 was required for an additional 48 hours to obtain maximal effect. CONCLUSIONS: Clinically relevant concentrations of actinomycin D act synergistically with ABT-737 to induce SCLC apoptosis, which can be at least partially attributed to the actinomycin D-induced decrease in Mcl-1 and increase in Noxa expression. Taken together, these data suggest the feasibility of combining actinomycin D with BH3-mimetic drugs in the clinical setting.

[Laparoscopic ultrasonography in laparoscopic hepatectomy: experience with 22 cases].

OBJECTIVE: To assess the value of laparoscopic ultrasonography in laparoscopic hepatectomy. METHODS: Twenty-two patients with liver diseases underwent laparoscopic ultrasonography. A 10 mm 7.5/10 MHz linear, side viewing laparoscopic ultrasonography probe was used intra-operatively to examine the convergence of intrahepatic biliary ducts and blood vessels, confirm and correct the resection line, guide the laparoscopic resection, examine the tumor margin, and discover the residue of calculi. RESULTS: One additional tumor was detected in one primary liver tumor case during the laparoscopic hepatectomy. Laparoscopic hepatectomy was accomplished successfully in 21 patients one of which had to be transferred to laparotomy due to severe liver cirrhosis and uncontrollable bleeding. The average operation time was 157 min with the average examining and guiding time of 14 min. The intra-operative bleeding amount was 520 ml. No calculus and tumor residue were found. One case of post-operative liver wound bile leakage and one case of subphrenic hydrops were found and they both recovered after drainage. CONCLUSION: Intra-operative laparoscopic ultrasonography helps evaluate the entire liver and decide the resection line accurately. Under its guiding the laparoscopic hepatectomy can be performed smoothly.

alpha-Zearalanol attenuates oxLDL-induced ET-1 gene expression, ET-1 secretion and redox-sensitive intracellular signaling activation in human umbilical vein endothelial cells.

alpha-Zearalanol (alpha-ZAL), a phytochemical with both antioxidant and estrogen-like properties, has been shown to retard progression of atherosclerosis and regulate cardiovascular function in part through suppression of endothelin-1 (ET-1) secretion. However, the precise nature behind alpha-ZAL-elicited inhibition on ET-1 cascade is not largely known. Oxidized low density lipoprotein (oxLDL) plays a critical role in the expression and secretion of ET-1 as well as the onset and progression of atherosclerosis through accumulation of reactive oxygen species (ROS) and activation of mitogen-activated protein kinase stress signaling cascade. Therefore, this study was designed to examine the effect of alpha-ZAL on oxLDL-induced extracellular signal-regulated kinase (ERK) phosphorylation, ROS generation, activation of the transcriptional factor activator protein-1 (AP-1), expression, secretion and promoter activity of ET-1 in human umbilical vein endothelial cells (HUVEC). ROS generation was monitored using 2,7-dichlorofluorescin fluorescence. ET-1 expression and promoter activity were evaluated by RT-PCR and luciferase assays, respectively. oxLDL (35 microg/ml) significantly enhanced ERK phosphorylation, ROS generation, AP-1 activity, mRNA expression, secretion and promoter activity of ET-1 in HUVECs, all of which were abrogated by alpha-ZAL and the antioxidant N-acetyl-l-cysteine. Collectively, these data favor the notion that alpha-ZAL antagonizes oxLDL-induced upregulation of ET-1 gene expression and secretion via suppression of oxLDL-induced ROS accumulation, ERK phosphorylation, and activation of the endothelial transcriptional factor AP-1.

Reactive oxygen species mediate oxidized low-density lipoprotein-induced endothelin-1 gene expression via extracellular signal-regulated kinase in vascular endothelial cells.

BACKGROUND: Oxidized low-density lipoprotein (oxLDL) promotes expression and secretion of endothelin-1 (ET-1), however, the precise mechanism involved is unclear. This study was designed to identify the regulatory mechanism of oxLDL-induced ET-1 expression in endothelial cells. METHODS: ET-1 mRNA expression, secretion and promoter activity were evaluated by reverse transcriptase-PCR (RT-PCR), enzyme immunometric and luciferase assays, respectively. RESULTS: oxLDL (35 microg/ml) significantly enhanced reactive oxygen species (ROS), mRNA expression, secretion and promoter activity of ET-1 in human umbilical vein endothelial cells (HUVECs), all of which were nullified by the antioxidant N-acetyl cysteine (NAC). oxLDL stimulated the extracellular signal-regulated kinase (ERK) phosphorylation in HUVECs, which was blocked by NAC and the mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor PD98059. NAC and PD98059 stopped oxLDL-elicited increase in mRNA expression, secretion and promoter activity of ET-1. Fusion plasmids with decreasing length of 5'-flanking sequence of ET-1 from -566 bpLuc to -250 bpLuc displayed increased luciferase activity after 24 h of oxLDL treatment. Interestingly, fusion plasmid from -233 and -185 bpLuc significantly reduced the luciferase activity in control and oxLDL-treated HUVECs. In addition, transfection of the reporter construct -250Luc, which contains a 2 bp mutation at activator protein-1 site, abolished both basal and oxLDL-stimulated ET-1 promoter activities. CONCLUSION: Collectively, our data favor the notion that oxLDL stimulates ERK phosphorylation via ROS accumulation, which in turn stimulates vascular endothelial transcriptional factor activator protein-1 and ET-1 expression as well as secretion.

RETRACTED: Phytoestrogen alpha-zearalanol inhibits homocysteine-induced endothelin-1 expression and oxidative stress in human umbilical vein endothelial cells.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. After an institutional investigation into the work of Dr. Jun Ren, University of Wyoming subsequently conducted an examination of other selected publications of Dr. Ren's under the direction of the HHS Office of Research Integrity. Based on the findings of this examination, the University of Wyoming recommended this article be retracted due to data irregularities in Figures 3 and 5 that significantly affect the results and conclusions reported in the manuscript.