Metabolome and Transcriptome Profiling Reveals the Function of MdSYP121 in the Apple Response to Botryosphaeria dothidea.

The vesicular transport system is important for substance transport in plants. In recent years, the regulatory relationship between the vesicular transport system and plant disease resistance has received widespread attention; however, the underlying mechanism remains unclear. MdSYP121 is a key protein in the vesicular transport system. The overexpression of MdSYP121 decreased the B. dothidea resistance of apple, while silencing MdSYP121 resulted in the opposite phenotype. A metabolome and transcriptome dataset analysis showed that MdSYP121 regulated apple disease resistance by significantly affecting sugar metabolism. HPLC results showed that the levels of many soluble sugars were significantly higher in the MdSYP121-OE calli. Furthermore, the expression levels of genes related to sugar transport were significantly higher in the MdSYP121-OE calli after B. dothidea inoculation. In addition, the relationships between the MdSYP121 expression level, the soluble sugar content, and apple resistance to B. dothidea were verified in an F1 population derived from a cross between 'Golden Delicious' and 'Fuji Nagafu No. 2'. In conclusion, these results suggested that MdSYP121 negatively regulated apple resistance to B. dothidea by influencing the soluble sugar content. These technologies and methods allow us to investigate the molecular mechanism of the vesicular transport system regulating apple resistance to B. dothidea.

Laparoscopic common bile duct exploration with primary closure is beneficial for patients with previous upper abdominal surgery.

BACKGROUND: Previous upper abdominal surgery (PUAS) is considered a contraindication to laparoscopic surgery. Whether LCBDE-PC is feasible and beneficial for patients with PUAS remains unclear. This study aimed to evaluate the feasibility and benefits of LCBDE-PC for patients with PUAS. METHODS: From June 2011 to September 2019, 1167 patients who underwent laparoscopic procedures for choledocholithiasis were reviewed retrospectively. Perioperative outcomes were compared between patients with and without PUAS in un-matched and matched cohorts. RESULTS: LCBDE-PC was performed successfully in 88.3% of patients with PUAS, and 92.5% of patients without PUAS (P > 0.05). Multivariate analysis showed that PUAS was not a risk factor that affected successful performance of LCBDE-PC. Although a higher rate of conversion to open surgery and longer operative time were observed in patients with PUAS, no significant differences were found between patients with and without PUAS in multivariate and propensity score analysis (P > 0.05). A predictive nomogram for LCBDE-PC failure was developed based on potential predictors from the least absolute shrinkage and selection operator (LASSO) regression model. Successful performance of LCBDE-PC was associated with operative time. A linear regression model for operative time showed impacted stone in the CBD and intraoperative laser use was the most important factor in determining the operative time. CONCLUSION: LCBDE-PC is feasible and beneficial for patients with PUAS. However, patients with PUAS with a high possibility of LCBDE-PC failure from the nomogram and a longer operative time from the linear regression model should be cautious when undergoing LCBDE-PC.

Risk factors and consequences of conversion to open surgery in laparoscopic common bile duct exploration.

BACKGROUND: Although laparoscopic common bile duct exploration (LCBDE) has shown many obvious advantages compared with open surgery in the treatment of common bile duct (CBD) stones, it remains unclear regarding risk factors of conversion from LCBDE to open surgery and whether conversion will counteract the advantages of LCBDE. The purpose of this study was to explore risk factors and consequences of conversion from LCBDE to open surgery. METHODS: A retrospective study was conducted, using a database of 644 patients with LCBDE between 2011 and 2017. Risk factors for conversion to open surgery were determined based on univariable and multivariable analysis. The consequences of conversion to open surgery in LCBDE were analyzed. RESULTS: Conversion was required in 27 (4.2%) of 644 patients undergoing LCBDE. Independent risk factors for conversion were as follows: the max diameter of stones in CBD (odds ratio (OR) 2.234, 95%CI 1.031-4.842; p = 0.042), edema of CBD (OR 12.530, 95%CI 4.633-33.887; p < 0.001), and multiple stones in CBD (OR 3.438, 95%CI: 1.133-10.428; p = 0.029). These risk factors and their combined were good predictors for conversion in LCBDE. More blood loss, longer operative time, longer postoperative hospital stay, and higher incision infection were identified in patients with conversion than those without conversion. However, no significant differences were observed regarding mortality, readmission within 30 days, reoperation, bile leakage, and intra-abdominal fluid collection. CONCLUSION: Conversion to open surgery in LCBDE was associated with acute edematous CBD with large and multiple stones. Conversion can offset the advantages of LCBDE.

Absorbable Versus Nonabsorbable Sutures for Skin Closure: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Prior studies focused on skin closure using absorbable or nonabsorbable sutures involved small samples and produced conflicting results. The optimal method of skin closure still remains unclear. OBJECTIVE: This study aimed to compare the outcomes of absorbable versus nonabsorbable sutures for skin closure. METHODS: A meta-analysis was performed in randomized controlled trials (RCTs) that compared outcomes of absorbable versus nonabsorbable sutures for skin closure. RESULTS: A total of 1748 patients in 19 RCTs were analyzed. There was no significant difference between absorbable sutures and nonabsorbable sutures in the incidence of wound infections, cosmetic outcomes, scar formation, wound dehiscence, and patients' or patient caregivers' satisfaction. Better cosmetic results were achieved by using intradermal absorbable sutures compared with nonabsorbable sutures in subgroup analysis, but this result might be affected by insufficient follow-ups. CONCLUSIONS: Absorbable sutures for skin closure were not inferior to nonabsorbable sutures. It should be recommended due to its great cost and time savings. Well-designed RCTs with sufficient follow-ups are needed to adequately clarify whether better cosmetic results can be achieved using intradermal absorbable sutures.

Structural characterization of a water-soluble acidic polysaccharide CSP-IV with potential anticoagulant activity from fruit pulp of Clausena lansium (Lour.) Skeels Guifei.

Four main water-soluble wampee fruit pulp polysaccharides, named CSP-I, CSP-II, CSP-III and CSP-IV, were isolated from Clausena lansium (Lour.) Skeels Guifei, therein CSP-IV content was higher than the others. All components possess certain anticoagulant activity demonstrated by prolonged activated partial thromboplastin time, especially CSP-IV, which suggests that CSP-IV plays anticoagulant effect through disturbing intrinsic coagulation pathway. The wampee polysaccharide CSP-IV with Mw of 510.1 kDa was mainly composed of Gal, Ara and GalA. Backbone of CSP-IV contains Gal, Ara and GalA, two kinds of side chains contain one monosaccharide Gal or Ara, both branch on Gal residue of backbone. CSP-IV has no the conformation of triple helix demonstrated by Congo red test. These results showed that CSP-IV is an acidic polysaccharide with potential anticoagulant activity via targeting intrinsic coagulation pathway.

Reversible Growth of Halide Perovskites via Lead Oxide Hydroxide Nitrates Anchored Zeolitic Imidazolate Frameworks for Information Encryption and Decryption.

The low formation energies of metal halide perovskites endow them with potential luminescent materials for applications in information encryption and decryption. However, reversible encryption and decryption are greatly hindered by the difficulty in robustly integrating perovskite ingredients into carrier materials. Here, we report an effective strategy to realize information encryption and decryption by reversible synthesis of halide perovskites, on the lead oxide hydroxide nitrates (Pb13O8(OH)6(NO3)4) anchored zeolitic imidazolate framework composites. Benefiting from the superior stability of ZIF-8 in combination with the strong bond between Pb and N evidenced by X-ray absorption spectroscopy and X-ray photoelectron spectroscopy, the as-prepared Pb13O8(OH)6(NO3)4-ZIF-8 nanocomposites (Pb-ZIF-8) can withstand common polar solvent attack. Taking advantage of blade-coating and laser etching, the Pb-ZIF-8 confidential films can be readily encrypted and subsequently decrypted through reaction with halide ammonium salt. Consequently, multiple cycles of encryption and decryption are realized by quenching and recovery of the luminescent MAPbBr3-ZIF-8 films with polar solvents vapor and MABr reaction, respectively. These results provide a viable approach to integrate the state-of-the-art materials perovskites and ZIF for applications in information encryption and decryption films with large scale (up to 6 × 6 cm2), flexibility, and high resolution (approximate 5 µm line width).

Treatment of pancreatic cancer using an oncolytic virus harboring the lipocalin-2 gene.

BACKGROUND: The 5-year survival rate for patients with pancreatic cancer is <5%, and it is always resistant to the current chemoradiotherapy. Therefore, new, effective agents for the treatment of pancreatic cancer are urgently needed. The promising strategy of cancer-targeting gene virotherapy (CTGVT) has demonstrated great anticancer potential. The objective of the current study was to determine whether 1 CTGVT approach, oncolytic virus (OV)-harboring lipocalin-2, is capable of treating pancreatic cancer. METHODS: Tissue microarrays were constructed to detect the expression of lipocalin-2 in 60 specimens of pancreatic adenocarcinoma. The clinical significance of lipocalin-2 was investigated in an analysis of correlations between lipocalin-2 expression and matched clinical characteristics. A lipocalin-2-expressing OV, ZD55-lipocalin-2, was constructed by deleting the adenoviral protein E1B55kD. The antitumor efficacy and mechanisms of the OV were investigated in pancreatic cancer cells with v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in vitro and in vivo. RESULTS: Lipocalin-2 expression was correlated with a good prognosis in patients with pancreatic adenocarcinoma. ZD55-lipocalin-2 dramatically inhibited the growth of pancreatic cancer in vitro and in vivo by inducing cytolysis and caspase-dependent apoptosis. CONCLUSIONS: Higher lipocalin-2 expression predicted a better prognosis in patients with pancreatic cancer. The results indicated that ZD55-lipocalin-2, which specifically expressed higher levels of lipocalin-2 in tumor cells, may serve as a potent anticancer drug for pancreatic cancer therapy, especially for patients who have pancreatic adenocarcinoma with KRAS mutations.

Predictive value of serum carbohydrate antigen 19-9 in malignant intraductal papillary mucinous neoplasms.

BACKGROUND: The goal of the present study was to evaluate the predictive value of serum carbohydrate antigen 19-9 (CA 19-9) in the diagnosis of malignant intraductal papillary mucinous neoplasms of pancreas (IPMNs). METHODS: Eighty-six patients with pathological diagnosis of IPMNs in Zhongshan Hospital between March 1999 and November 2008 were retrospectively reviewed. Data reflecting clinical characteristics, tumor marker level, and prognosis were collected. The potential predictive value of CA 19-9 was analyzed by receiver operating characteristic (ROC) curve. RESULTS: Eighty-six consecutive patients with IPMNs all underwent surgical intervention. A high level of CA 19-9 or carcinoembryonic antigen (CEA) was associated with more advanced stage of malignant IPMNs. Carbohydrate antigen 19-9 was significant for judging malignant IPMNs in the binary logistic regression model (p=0.047). The hazard ratio was 1.014, whose 95.0% confidence interval was 0.91-1.028. Receiver operating characteristic analysis showed that the serum CA 19-9 level had good predictive value for malignant or invasive IPMNs, postoperative survival, and disease-specific recurrence. The area under the curve (AUC) was 0.856, 0.893, 0.815, and 0.857 (p<0.05), respectively. According to the follow-up, mean survival time for groups with CA 19-9>63.60 U/ml was dramatically shorter than that for groups with CA 19-9≤63.60 U/ml (57.38±2.85 versus 29.24±5.82 [months]; p<0.01). CONCLUSIONS: Serum CA 19-9 level has good predictive value for malignant or invasive IPMNs. Patients with CA 19-9 > 63.60 U/ml had poor postoperative prognosis in IPMNs. Preoperative abnormal serum CA 19-9 might be predictive for an aggressive surgical intervention in IPMNs.

The expression of microRNA-340 and cyclin D1 and its relationship with the clinicopathological characteristics and prognosis of lung cancer.

BACKGROUND: To explore the expression of microribonucleic acid-340 (miR-340) and cyclin D1 (CCND1) in lung cancer (LC) tissues and its relationship with the clinicopathological characteristics and prognosis of LC. METHODS: Cancer tissues and paracancerous normal lung tissues of 65 patients with LC admitted to our hospital from January 2014 to March 2015 were included as the LC group, and the paracancerous group, respectively. RESULTS: The relative expression levels of miR-340 mRNA and miR-340 protein in the LC group were lower than those in the paracancerous group, while the relative expression levels of CCND1 mRNA and CCND1 protein in the LC group were higher than those in the paracancerous group (P < 0.05). Pearson correlation analysis results showed that the mRNA and protein expression of both miR-340 and CCND1 in LC tissues was negatively correlated (r < 0, P < 0.05).The high expression rate (HER) of miR-340 and high expression rate (PER) of CCND1 were related to the tumor size, lymph node metastasis, TNM staging, and degree of differentiation (P < 0.05). The patients with high expression (HE) of miR-340 showed increased 5-year SR compared with the patients with low expression of miR-340, and that of patients positive for CCND1 was lower than that of the patients negative for CCND1 (P < 0.05). CONCLUSION: miR-340 was downregulated, whereas CCND1 was upregulated in LC tissues, and the expression levels of the two genes were closely related to the prognosis and clinicopathological characteristics of LC.

Removal of CSF pixels on brain MR perfusion images using first several images and Otsu's thresholding technique.

Brain MR perfusion imaging is used to evaluate local perfusion in patients with cerebral vascular disease. Quantitative measurements on the hemodynamic parameters and volume of brain with abnormal perfusion provide an estimation of the severity of the brain perfusion defect. However, quantitative measurements of these focal cerebral hemodynamic parameters are limited by the presence of cerebrospinal fluid (CSF) pixels. We noticed that the CSF has a higher signal than other tissue types on the first perfusion image, which is usually discarded in routine parametric image calculations. This signal difference, however, can be used to segment CSF pixels on the perfusion images. An image division was used to generate ratio images to compensate for spatially dependent signal variation caused by the inhomogeneity of excitation radiofrequency field. By applying an appropriate signal threshold to the ratio images, CSF pixels can be identified and removed from the parametric images. With the removal of CSF pixels, the volume of delayed-perfusion brain parenchyma can be better visualized and the interference from the CSF can be avoided. The proposed technique is simple, fast, automatic, and effective, and no extra scanning is needed to use this technique.

A new fluorescent chemosensor detecting Co2+ and K+ in DMF buffered solution.

A new fluorescent chemosensor 2-(2-thiophene)imidazo [4,5,f]-1,10-phenanthroline (L) was prepared and characterized. By adding univalent or divalent metal ions such as Na(+), K(+), Mg(2+), Ba(2+), Mn(2+), Fe(2+), Co(2+), Ni(2+), Cu(2+), Ag(+), Zn(2+), Cd(2+) and Hg(2+) ions into the solution of L in DMF under buffered conditions with the working pH ranging from 7.0 to 8.0, we found that L could be used to detect K(+) ratiometricly and it could also be applied to sense Co(2+) with the phenomenon of fluorescence quenching of L. While the response behavior of L was not discernibly affected by other examined metal ions.

The Roles of Endoplasmic Reticulum in NLRP3 Inflammasome Activation.

The NLRP3 (nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3) inflammasome senses pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs), and activates caspase-1, which provokes release of proinflammatory cytokines such as interleukin-1ß (IL-1ß) and IL-18 as well as pyroptosis to engage in innate immune defense. The endoplasmic reticulum (ER) is a large and dynamic endomembrane compartment, critical to cellular function of organelle networks. Recent studies have unveiled the pivotal roles of the ER in NLRP3 inflammasome activation. ER-mitochondria contact sites provide a location for NLRP3 activation, its association with ligands released from or residing in mitochondria, and rapid Ca2+ mobilization from ER stores to mitochondria. ER-stress signaling plays a critical role in NLRP3 inflammasome activation. Lipid perturbation and cholesterol trafficking to the ER activate the NLRP3 inflammasome. These findings emphasize the importance of the ER in initiation and regulation of the NLRP3 inflammasome.

Quantitative trait loci-based genomics-assisted prediction for the degree of apple fruit cover color.

Apple fruit cover color is an important appearance trait determining fruit quality, high degree of fruit cover color or completely red fruit skin is also the ultimate breeding goal. MdMYB1 has repeatedly been reported as a major gene controlling apple fruit cover color. There are also multiple minor-effect genes affecting degree of fruit cover color (DFC). This study was to identify genome-wide quantitative trait loci (QTLs) and to develop genomics-assisted prediction for apple DFC. The DFC phenotype data of 9,422 hybrids from five full-sib families of Malus asiatica 'Zisai Pearl', M. domestica 'Red Fuji', 'Golden Delicious', and 'Jonathan' were collected in 2014-2017. The phenotype varied considerably among hybrids with the same MdMYB1 genotype. Ten QTLs for DFC were identified using MapQTL and bulked segregant analysis via sequencing. From these QTLs, ten candidate genes were predicted, including MdMYB1 from a year-stable QTL on chromosome 9 of 'Zisai Pearl' and 'Red Fuji'. Then, kompetitive allele-specific polymerase chain reaction (KASP) markers were designed on these candidate genes and 821 randomly selected hybrids were genotyped. The genotype effects of the markers were estimated. MdMYB1-1 (represented by marker H162) exhibited a partial dominant allelic effect on MdMYB1-2 and showed non-allelic epistasis on markers H1245 and G6. Finally, a non-additive QTL-based genomics assisted prediction model was established for DFC. The Pearson's correlation coefficient between the genomic predicted value and the observed phenotype value was 0.5690. These results can be beneficial for apple genomics-assisted breeding and may provide insights for understanding the mechanism of fruit coloration.

Genome Sequences of Three Apple chlorotic leaf spot virus Isolates from Hawthorns in China.

The genome sequences of Apple chlorotic leaf spot virus (ACLSV) isolates from three accessions of hawthorns (Crataegus pinnatifida) grown at Shenyang Agricultural University were determined using Illumina RNA-seq. To confirm the assembly data from the de novo sequencing, two ACLSV genomic sequences (SY01 and SY02) were sequenced using the Sanger method. The SY01 and SY02 sequences obtained with the Sanger method showed 99.5% and 99.7% nucleotide identity with the transcriptome data, respectively. The genome sequences of the hawthorn isolates SY01, SY02 and SY03 (GenBank accession nos. KM207212, KU870524 and KU870525, respectively) consisted of 7,543, 7,561 and 7,545 nucleotides, respectively, excluding poly-adenylated tails. Sequence analysis revealed that these hawthorn isolates shared an overall nucleotide identity of 82.8-92.1% and showed the highest identity of 90.3% for isolate YH (GenBank accession no. KC935955) from pear and the lowest identity of 67.7% for isolate TaTao5 (GenBank accession no. EU223295) from peach. Hawthorn isolate sequences were similar to those of 'B6 type' ACLSV. The relationship between ACLSV isolates largely depends upon the host species. This represents the first comparative study of the genome sequences of ACLSV isolates from hawthorns.

Increased water salinity applied to tomato plants accelerates the development of the leaf miner Tuta absoluta through bottom-up effects.

Variation in resource inputs to plants may trigger bottom-up effects on herbivorous insects. We examined the effects of water input: optimal water vs. limited water; water salinity: with vs. without addition of 100 mM NaCl; and their interactions on tomato plants (Solanum lycopersicum), and consequently, the bottom-up effects on the tomato leaf miner, Tuta absoluta (Meytick) (Lepidoptera: Gelechiidae). Plant growth was significantly impeded by limited water input and NaCl addition. In terms of leaf chemical defense, the production of tomatidine significantly increased with limited water and NaCl addition, and a similar but non-significant trend was observed for the other glycoalkaloids. Tuta absoluta survival did not vary with the water and salinity treatments, but the treatment "optimal water-high salinity" increased the development rate without lowering pupal mass. Our results suggest that caution should be used in the IPM program against T. absoluta when irrigating tomato crops with saline water.

Braun Enteroenterostomy Following Pancreaticoduodenectomy: A Systematic Review and Meta-Analysis.

Pancreaticoduodenectomy (PD) holds high postoperative morbidity. How to resolve this issue is challenged. An additional anastomosis (Braun enteroenterostomy) following PD may decrease the postoperative morbidity, but holds conflicting results. The objective of this study is to investigate the advantages and disadvantages of Braun enteroenterostomy in PD.Clinical studies compared perioperative outcomes between the Braun group and the non-Braun group following PD before December 21, 2014 were retrieved and filtered from PubMed, EMBASE, Web of Science, the Cochrane Library, and Chinese electronic databases (VIP database, WanFang database, and CNKI database). Relevant data were extracted according to predesigned sheets. Blood loss, operating time, and postoperative mortality and morbidity were evaluated using odds ratio (OR), weighted mean difference, or standard mean difference (SMD).Ten studies concerning 1614 patients were included. No significant differences between the Braun and the non-Braun group were identified in mortality (OR: 0.65, 95% confidence interval [CI]: 0.26-1.60), intraoperative blood loss (SMD: -0.035, 95% CI: -0.253 to 0.183), postoperative pancreatic fistula (POPF) (OR: 0.67, 95% CI: 0.35-1.67), bile leakage (OR: 0.537, 95% CI: 0.287-1.004), postoperative gastrointestinal hemorrhage (OR: 1.17, 95% CI: 0.578-2.385), intraabdominal abscesses (OR: 0.793, 95% CI: 0.444-1.419), wound complications (OR: 0.806, 95% CI: 0.490-1.325), and hospital stay (SMD: -0.098, 95% CI: -0.23 to 0.033). Braun enteroenterostomy extended operating time (SMD: 0.39, 95% CI: 0.02-0.78), but it was associated with lower reoperation rate (OR: 0.380, 95% CI: 0.149-0.968), lower morbidity rate (OR: 0.66, 95% CI: 0.49-0.91), lower clinically relevant delayed gastric emptying (Grades B and C) (OR: 0.375, 95% CI: 0.164-0.858), lower nasogastric tube reinsertion (OR: 0.436, 95% CI: 0.232-0.818), and less postoperative vomiting (OR: 0.444, 95% CI: 0.262-0.755).Braun enteroenterostomy can be safely performed during PD. It is beneficial for patients and could be recommended in PD from the current published data.PROSPERO registration number: CRD42015016198.

Transvaginal cholecystectomy vs conventional laparoscopic cholecystectomy for gallbladder disease: A meta-analysis.

AIM: To compare the results of transvaginal cholecystectomy (TVC) and conventional laparoscopic cholecystectomy (CLC) for gallbladder disease. METHODS: We performed a literature search of PubMed, EMBASE, Ovid, Web of Science, Cochrane Library, Google Scholar, MetaRegister of Controlled Trials, Chinese Medical Journal database and Wanfang Data for trials comparing outcomes between TVC and CLC. Data were extracted by two authors. Mean difference (MD), standardized mean difference (SMD), odds ratios and risk rate with 95%CIs were calculated using fixed- or random-effects models. Statistical heterogeneity was evaluated with the χ(2) test. The fixed-effects model was used in the absence of statistically significant heterogeneity. The random-effects model was chosen when heterogeneity was found. RESULTS: There were 730 patients in nine controlled clinical trials. No significant difference was found regarding demographic characteristics (P > 0.5), including anesthetic risk score, age, body mass index, and abdominal surgical history between the TVC and CLC groups. Both groups had similar mortality, morbidity, and return to work after surgery. Patients in the TVC group had a lower pain score on postoperative day 1 (SMD: -0.957, 95%CI: -1.488 to -0.426, P < 0.001), needed less postoperative analgesic medication (SMD: -0.574, 95%CI: -0.807 to -0.341, P < 0.001) and stayed for a shorter time in hospital (MD: -1.004 d, 95%CI: -1.779 to 0.228, P = 0.011), but had longer operative time (MD: 17.307 min, 95%CI: 6.789 to 27.826, P = 0.001). TVC had no significant influence on postoperative sexual function and quality of life. Better cosmetic results and satisfaction were achieved in the TVC group. CONCLUSION: TVC is safe and effective for gallbladder disease. However, vaginal injury might occur, and further trials are needed to compare TVC with CLC.

One potential oncolytic adenovirus expressing Lipocalin-2 for colorectal cancer therapy.

Colorectal cancer is an aggressive malignancy with a high mortality rate; however, effective therapies are currently lacking. Cancer-targeting gene-virotherapy (CTGVT) has been proposed to be a promising strategy for cancer therapy. The purpose of this study was to investigate the antitumor activity of the oncolytic adenovirus harboring Lipocalin-2 (ZD55-Lipocalin-2, an example of CTGVT) in colorectal cancer. ZD55-Lipocalin-2 was generated by deleting E1B55-KD and inserting the Lipocalin-2 gene. Its cytopathic effects and cell growth inhibition were detected in vitro, and antitumor effects were examined in a nude mouse model of human colorectal cancer xenografts. Results showed that ZD55-Lipocalin-2 significantly inhibited the colorectal cancer growth by selective cytolysis, inducing apoptosis and decreasing the microvessel density in tumors. The anticancer potential of ZD55-Lipocalin-2 showed stronger than that of the isolated Lipocalin-2 gene therapy or isolated ZD55 oncolytic adenovirus therapy. ZD55-Lipocalin-2 may serve as a potential anticancer agent for colorectal cancer treatment.

Toxicokinetics of naringin, a putative antitussive, after 184-day repeated oral administration in rats.

The toxicokinetic characteristics of naringin were investigated in rats that had been orally administered naringin extract, a candidate for oral treatment of cough, prepared from Citrus grandis "Tomentosa", at 50, 250, or 1250 mg/kg/day in a repeated-dose study for 1, 32, 93, or 184 days. Increased values of the mean systemic exposure were approximately proportional to increases in dose levels during all collection intervals; no saturation was observed. No significant differences in mean systemic exposure were observed between male and female rats. Results provide a reference for interpretation of toxicology findings and relevance to clinical safety issues.