Diallyl trisulfide suppresses tumor growth through the attenuation of Nrf2/Akt and activation of p38/JNK and potentiates cisplatin efficacy in gastric cancer treatment.

Diallyl trisulfide (DATS), a garlic organosulfide, has shown excellent chemopreventive potential. Cisplatin (DDP) is widely used to treat solid malignant tumors, but causing serious side effects. In the current study, we attempted to elucidate the chemopreventive mechanisms of DATS in human gastric cancer BGC-823 cells in vitro, and to investigate whether DATS could enhance the anti-tumor efficacy of DDP and improve quality of life in BGC-823 xenograft mice in vivo. Treatment with DATS (25-400 µmol/L) dose-dependently inhibited the viability of BGC-823 cells in vitro with an IC50 of 115.2±4.3 µmol/L after 24 h drug exposure. DATS (50-200 µmol/L) induced cell cycle arrest at G2/M phase in BGC-823 cells, which correlated with significant accumulation of cyclin A2 and B1. DATS also induced BGC-823 cell apoptosis, which was accompanied by the modulation of Bcl-2 family members and caspase cascade activation. In BGC-823 xenograft mice, administration of DATS (20-40 mg·kg-1·d-1, ip) dose-dependently inhibited tumor growth and markedly reduced the number of Ki-67 positive cells in tumors. Interestingly, combined administration of DATS (30 mg·kg-1·d-1, ip) with DDP (5 mg/kg, every 5 d, ip) exhibited enhanced anti-tumor activity with fewer side effects. We showed that treatment of BGC-823 cells with DATS in vitro and in vivo significantly activated kinases such as p38 and JNK/MAPK and attenuated the Nrf2/Akt pathway. This study provides evidence that DATS exerts anticancer effects and enhances the antitumor efficacy of DDP, making it a novel candidate for adjuvant therapy for gastric cancer.

Bi-phase CT radiomics nomogram for the preoperative prediction of pylorus lymph node metastasis in non-pyloric gastric cancer patients.

BACKGROUND: The expansion of function-preserving surgery became possible due to a more profound understanding of gastric cancer (GC), and T1N + or T2N + gastric cancer patients might be potential beneficiaries. However, ways to evaluate the possibility of function-preserving pylorus surgery are still unknown. METHODS: A total of 288 patients at Renji Hospital and 58 patients at Huadong Hospital, pathologically diagnosed with gastric cancer staging at T1 and T2 with tumors located in the upper two-thirds of the stomach, were retrospectively enrolled from March 2015 to October 2022. Tumor regions of interest (ROIs) were manually delineated on bi-phase CT images, and a nomogram was built and evaluated. RESULTS: The radiomic features distributed differently between positive and negative pLNm groups. Two radiomic signatures (RS1 and RS2) and one clinical signature were constructed. The radiomic signatures exhibited good performance for discriminating pLNm status in the test set. The three signatures were then combined into an integrated nomogram (IN). The IN showed good discrimination of pLNm in the Renji cohort (AUC 0.918) and the Huadong cohort (AUC 0.649). The verification models showed high values. CONCLUSION: For GC patients with T1 and T2 tumors located in the upper two-thirds of the stomach, a nomogram was successfully built for predicting pylorus lymph node metastasis, which would guide the surgical indication extension of conservative gastrectomies.

[Clinical study of repairing donor site of thickness from cicatricial skin with auto-scalp grafting].

OBJECTIVE: To study the effects of using auto-scalp for repairing donor site of thickness from cicatricial skin with auto-scalp grafting. METHODS: A total of 13 cases with donor site of thickness from cicatricial skin from January 2011 to December 2011 were analyzed. Wounds of donor site from cicatricial skin were grafted with auto-scalp and scalp were fixation was applied with negative pressure. The survival rate of auto-scalp graft was observed at Day 7 post-operation. At Month 12, hyperplastic scars at these donor sites of cicatricial skin were assessed through Vancouver Scar Assessment Table, scar itch assessment and scar proliferation rate. Wounds in the other thirteen cases with donor site of thickness from cicatricial skin from January 2010 to December 2010 were covered with vaseline gauze as control. RESULTS: No significant difference existed in the gender and age of the two groups patients (P > 0.05). The auto-scalp graft all survived. And the average healing time of donor-site wound in cicatricial skin in grafting group (7 days) was significantly decreased than that of control group (a mean of 20 days) (P < 0.01). After followed up for twelve months, the scar formation assessment value (1.5 ± 0.5), scar itch assessment (1.2 ± 0.4) and scar proliferation rate (14.6% ± 7.6%) in grafting group were significantly less than those of control group (6.7 ± 1.1, 2.0 ± 0.7, 55.8% ± 12.2%, all P < 0.01). CONCLUSION: Auto-scalp grafting may greatly shorten the healing procedure and ameliorate the quality of donor-site of thickness from cicatricial skin.

[Early changes in serum neutrophil elastase in rats with burn, blast injury or combined burn-blast injury and its significance].

OBJECTIVE: To explore the early changes in serum neutrophil elastase (NE) in rats with burn, blast injury or combined burn-blast injury and its significance. METHODS: A total of 176 male Sprague Dawley rats were randomly divided into four groups: control (C), burn (BU), blast injury (BL) and burn-blast combined injury (BB). Rats in C group were not injured. Animals in BU group were subjected to 25% TBSA full-thickness burn on back with 94 degrees C water for 12 seconds; Animals in BL group were inflicted with moderate blast injury with 5 g 8701 compressed dynamite stick as the explosion source 75 cm away while left chest facing the explosive source; Rats in BB group were burned immediately after the blast injury similarly as in BL group. During the first 24 h post-injury, animals in BU and BB groups received intraperitoneal injection of sodium lactate Ringer's solution at a dose of 50 ml x kg(-1) x 12 h(-1). Protein concentration in bronchoalveolar lavage fluid (BALF), water content of lung tissue and NE content in serum were determined at 0 h (C group), 3 h, 6 h, 12 h, 1 d, 2 d, 3 d, 7 d post-injury. RESULTS: Protein concentration in BALF, water content of lung tissue and NE content in serum in SD rats of the injured groups were significantly higher than those in C group (P < 0.01 or P < 0.05), peaked within 2 d post-injury, especially at 2 d post-injury (NE content in serum: BU group, 319. 85 +/- 19.50 ng/ml; BL group, 467.43 +/- 31.64 ng/ml; BB group, 626.00 +/- 26.38 ng/ml vs. C group, 78.53 +/- 25.10 ng/ml). Overall, protein concentration in BALF, water content of lung tissue and NE content in serum in BB group were significantly higher than BU and BL groups (P < 0.01 or P < 0.05). Correlation analysis showed that within 3 d postinjury, a significant positive correlation was found between the protein concentration in BALF, water content of lung tissue and NE content in serum (r = 0.7910, 0.8078, P < 0.05) in BU group. NE content in serum and protein concentration in BALF were significantly positively correlated in BB group (r = 0.8672, P < 0.05). CONCLUSION: NE may play an important role in early lung injury of burn or blast injury, especially in combined burn-blast injury.

Near-Infrared Spectrum Detection of Wheat Gluten Protein Content Based on a Combined Filtering Method.

To eliminate the random error of the derivative near-IR (NIR) spectrum and to improve model stability and the prediction accuracy of the gluten protein content, a combined method is proposed for pretreatment of the NIR spectrum based on both empirical mode decomposition and the wavelet soft-threshold method. The principle and the steps of the method are introduced and the denoising effect is evaluated. The wheat gluten protein content is calculated based on the denoised spectrum, and the results are compared with those of the nine-point smoothing method and the wavelet soft-threshold method. Experimental results show that the proposed combined method is effective in completing pretreatment of the NIR spectrum, and the proposed method improves the accuracy of detection of wheat gluten protein content from the NIR spectrum.

The formation of an ordered microporous aluminum-based material mediated by phthalic acid.

By using phthalic acid as a soft template, we showed that it was possible to prepare a microporous aluminum-based material when the precipitation of Al(3+) was properly controlled. We also identified that this microporous aluminum-based material could be promising for the removal of fluoride ions in water treatment.

[Efficacy observation on application of negative pressure therapy in the treatment of superficial partial-thickness scald wound in children].

OBJECTIVE: To observe the effect of negative pressure therapy in the treatment of superficial partial-thickness scald in children. METHODS: Three hundred and seven children with superficial partial-thickness scald hospitalized from August 2009 to May 2012 were divided into negative pressure therapy group (NPT, n = 145) and control group (C, n = 162) according to the random number table. Patients in group NPT were treated with negative pressure from within post injury day (PID) 3 to PID 9 (with -16 kPa pressure), while traditional occlusive dressing method was used in group C. Changes in body temperature, wound healing condition, frequency of dressing change were compared between group NPT and group C. Bacterial culture results of wounds were compared before and after treatment in group NPT. Volume of drained transudate per one percent of wound area was recorded in group NPT on PID 1 to PID 3. Data were processed with t test or chi-square test. RESULTS: The incidence of high fever was significantly lower in group NPT (26.9%, 39/145) than in group C (63.6%, 103/162, χ(2) = 41.419, P < 0.01). On PID 9, complete wound epithelization was observed in 138 patients in group NPT, and in 7 patients there were a few residual wounds which healed after dressing change for 2 days. The wound healing time of patients in group NPT [(9.2 ± 0.6) d] was obviously shorter than that in group C [(10.1 ± 1.6) d, t = 6.895, P < 0.01]. The frequency of dressing change among patients in group NPT [(2.05 ± 0.22) times] was significantly decreased as compared with that in group C [(4.82 ± 0.81) times, t = 39.878, P < 0.01]. Bacteria were found in wound secretion of seventeen patients in group NPT before treatment, while no bacterium was discovered in all patients after treatment. Volumes of drainage fluid in group NPT were proportional to wound areas, which were respectively (9.8 ± 3.2), (6.2 ± 2.1), (4.1 ± 1.6) mL per one percent of wound area on PID 1, 2, and 3. CONCLUSIONS: NPT can decrease times of dressing change, and alleviate infection and inflammatory response by drainage of transudate, which promotes wound healing at last. NPT is proved to be a safe and effective approach for treatment of children with superficial partial-thickness scald.

Role of neutrophil elastase in lung injury induced by burn-blast combined injury in rats.

OBJECTIVE: Neutrophil elastase (NE) takes part in the pathogenesis of acute lung injury. However, its role in lung injury of burn-blast combined injury is unclear. Our objective was to assess the role of NE, and effect of sivelestat, a specific NE inhibitor, in lung injury induced by burn-blast combined injury in rats. METHODS: One hundred and sixty male Sprague-Dawley rats were randomly subjected to burn-blast combined injury (BB) group, burn-blast combined injury plus sivelestat treatment (S) group or control (C) group. Blood gas, protein concentration and NE activity in bronchoalveolar lavage fluid (BALF), pulmonary myeloperoxidase (MPO) activity, serum concentrations of TNF-α and IL-8, etc. were investigated from 0 h to 7 d post-injury. RESULTS: In BB group, PaO2 decreased, while NE activity in BALF, total protein concentration in BALF, pulmonary MPO activity and W/D ratio, serum concentrations of TNF-α and IL-8 increased with neutrophil infiltration, progressive bleeding and pulmonary oedema. Compared with BB group, sivelestat treatment decreased the NE activity and ameliorated the above indexes. CONCLUSION: Sivelestat, exerts a protective effect in lung injury after burn-blast combined injury through inhibiting NE activity to decrease pulmonary vascular permeability, neutrophil sequestration, and production of TNF-α and IL-8.

A novel model of burn-blast combined injury and its phasic changes of blood coagulation in rats.

Burn-blast combined injury has a complex pathological process that may cause adverse complications and difficulties in treatment. This study aims to establish a standard animal model of severe burn-blast combined injury in rats and also to investigate early phasic changes of blood coagulation. By using 54 Wistar rats, distance from explosion source (Hexogen) and size of burned body surface area were determined to induce severe burn-blast combined injury. Thereafter, 256 rats were randomly divided into four groups (n = 64): blast injury group, burn injury group, burn-blast combined injury group, and sham injury group. Gross anatomy and pathological changes in lungs were investigated at 3, 24, 72, and 168 h, respectively. Blood was also collected for analyzing coagulation parameters as prothrombin time, activated partial thromboplastin time, and plasma levels of fibrinogen, D-dimer, antithrombin III, and α2-antiplasmin from 0 to 168 h after injury. Severe burn-blast combined injury was induced by inflicting rats with a moderate blast injury when placing rats 75 cm away from explosion source and a full-thickness burn injury of 25% total body surface area. The rats with burn-blast combined injury had more severe lung injuries when compared with the other three groups. Pathological examination in the BBL group showed diffused alveolar hemorrhage, fluid filling, alveolar atelectasis, rupture and hyperplasia of partial alveolar septum, emphysema-like change, reduced capillary bed, and infiltration of extensive polymorphonuclear cells after injury. The blood of combined injured rats was in a hypercoagulable state within 24 h, shortly restored from 24 to 48 h, and rehypercoagulated from 48 to 72 h after injury. A secondary excessively fibrinolytic function was also found thereafter. The rat model of burn-blast combined injury was successfully established by simulating real explosion characteristics. Rats with burn-blast combined injuries suffered from more severe lung injuries and abnormal coagulation and fibrinolytic function than those induced by a burn injury or a blast injury component. Hence, a time-dependent treatment strategy on coagulation function should be emphasized in clinical therapy of burn-blast combined injury.

[Significance of plasmic L-plastin levels in the diagnosis of colorectal cancer].

OBJECTIVE: To investigate the clinical significance of plasmic L-plastin level in patients with colorectal cancer. METHODS: From March 2008 to March 2009, plasma samples were collected from 40 patients and 40 healthy controls. Plasmic L-plastin level was measured by ELISA kit and was compared to TIMP-1. RESULTS: Plasmic L-plastin level in patients with colorectal cancer was higher than that in healthy adults (1.662±0.386 vs. 0.485±0.085 µg/L, P<0.01). The sensitivity of L-plastin in the diagnosis of colorectal cancer was 67.5%, and the specificity was 80.6%. The Youden index was 0.481 and AUC was 0.772 (P<0.01). Plasmic L-plastin levels were associated with the tumor size (P=0.006), serosal penetration (F=4.687, P<0.05) and lymphatic metastasis (P<0.01). Compared to plasmic TIMP-1 level, L-plastin showed the same capability in indicating the depth of tumor. The specificity of L-plastin was better in indicating lymphatic metastasis (86% vs. 58%, χ2=4.2, P<0.05). CONCLUSIONS: Plasmic L-plastin level may serve as a potential marker in colorectal cancer.

Expression of cortactin correlates with a poor prognosis in patients with stages II-III colorectal adenocarcinoma.

BACKGROUND: The present study was designed to specifically investigate the clinicopathological role of expression of cortactin, as well as the correlation with clinical outcomes in stages II-III colorectal cancer (CRC). METHODS: Two hundred and five stages II-III CRC patients were included in this study. Formalin-fixed paraffin-embedded specimens were stained for cortactin and the correlation between the staining, its clinicopathological parameters, and its prognostic power were analyzed statistically. RESULTS: Of the 205 patients studied, 113 cases (55.1%) were strongly positive for cortactin. Cortactin expression correlated with tumor invasion (P = 0.018), histological grade (P = 0.004), and preoperative CEA level (P < 0.001). In univariate analysis, tumor invasion, American Joint Committee on Cancer (AJCC) stage, lymphovascular invasion, preoperative CEA level, and cortactin expression were significant prognostic factors for disease-free survival (P = 0.034, 0.009, 0.043, 0.004, and 0.004, respectively), while for overall survival, tumor invasion, AJCC stage, pathologic grade, preoperative CEA level, and cortactin expression were significant prognostic factors (P = 0.003, 0.008, 0.038, 0.017, and <0.001, respectively). In multivariate analysis, tumor invasion, preoperative CEA level, and cortactin expression maintained their independent prognostic influence on disease-free survival (P = <0.001, 0.003, and 0.008, respectively). However, tumor invasion, AJCC stage, and cortactin expression influenced overall survival (P = 0.036, <0.001, and 0.004, respectively). CONCLUSIONS: Cortactin may be a good biomarker to be applied in the clinical setting to predict the prognosis of patients with completely resected pathologic stages II-III CRC.

[Bt toxic protein expression in insect-resistant transgenic corns and its transfer to and accumulation in Ostrinia furnacalis].

Taking the insect-resistant transgenic corn varieties G03-2396 and G03-2739 and the conventional corn variety Suyu 16 as test materials, a bioassay in laboratory was conducted to test their resistance against Ostrinia furnacalis. The Bt toxin expression in different tissues of the two transgenic corns, the ingestion of Bt toxin by the 3rd and 5th instar of O. furnacalis, and the Bt toxin amount in feces of O. furnacalis larvae fed with Bt corns were analyzed by using enzyme-linked-immunosorbent-assay (ELISA). It was found that the central leaves of both G03-2396 and G03-2739 had great toxicity to O. furnacalis larvae. After fed with the central leaves for 6 d, the survival rate of neonate larvae was less than 3%, and that of the 3rd instar larvae was less than 70%. Female ears had smaller toxicity than central leaves. The Bt toxic protein was detected both in the leaves and in the female ears of the two transgenic corns, but its content was higher in central leaves than in female ears. The Bt toxic protein expression level was in order of G03-2739 central leaf (39.6 microg x g(-1) FM) > G03-2396 central leaf (26.1 microg x g(-1) FM) > G03-2396 female ear (17.0 microg x g(-1) FM) > G03-2739 female ear (14.6 microg x g(-1) FM). When fed with central leaf or female ear, the Bt toxic protein amount in the 3rd instar larvae was significantly higher than that in the 5th instar larvae. For the same age instar larvae, the Bt toxic protein content was significantly higher after fed with central leaf than fed with female ear, so did the Bt toxic protein content in larvae feces, being the highest (10.4 microg x g(-1) FM) for the 5th instar larvae fed with G03-2739 central leaf, and the lowest (2.7 microg x g(-1) FM) for the 3rd instar larvae fed with G03-2739 female ear.

Microsomal glutathione S-transferase gene polymorphisms and colorectal cancer risk in a Han Chinese population.

BACKGROUND AND AIMS: Glutathione S-transferases (GSTs) are phase II detoxification enzymes. Human GSTs have been classified into cytosolic, mitochondrial, and microsomal families. Several studies reported the association of colorectal cancer (CRC) risk with the genetic polymorphisms of cytosolic GSTs. The microsomal GSTs are structurally distinct but functionally similar to cytosolic GSTs; their association with CRC has not been reported. In this report, we summarized the result of a case-control study aimed at investigating the association of MGST1 gene locus polymorphisms with CRC risk among Han Chinese. PATIENT/METHODS: Three hundred and seventy-two healthy controls and 238 sporadic CRC patients participated in this study. DNA resequencing was conducted for the 3.4 kb genomic DNA region containing the promoter, exons, exon-intron junctions, and the 5' and 3' untranslated regions. RESULTS: We detected 13 single nucleotide polymorphisms (SNPs) including four novel SNPs not reported in database/literature. The gene shows a much higher nucleotide diversity than most human genes. The linkage and recombination analysis revealed 24 common haplotypes (13% > or = freq > or = 1%) and identified extensive intragenic recombination throughout the MGST1 locus (R = 81.8). Significant CRC association (P < or = 0.005) was not detected for each individual SNP. However, SNPs 102G>A and 16416G>A reached a marginal level of statistical significance with P values of 0.016 and 0.078, respectively. A combined genotype analysis detected a statistically significant CRC association for individuals carrying 102G>A/16416G>A (GG/GG) genotype (adjusted OR, 1.682; 95% confidence interval (CI), 1.177-2.404; P = 0.004). Consistent with the results of genotype analysis, the GG haplotype (102G>A/16416G>A) with two risk alleles was associated with a significantly higher CRC risk comparing with the haplotypes with one or no risk allele (adjusted OR 1.744; 95% CI 1.309-2.322; P = 0.0001). CONCLUSION: The results suggest that MGST1 polymorphisms may contribute to CRC risk among Han Chinese.

Enzymatic activity characterization of SARS coronavirus 3C-like protease by fluorescence resonance energy transfer technique.

AIM: To characterize enzymatic activity of severe acute respiratory syndrome (SARS) coronavirus (CoV) 3C-like protease (3CL(pro)) and its four site-directed mutants. METHODS: Based on the fluorescence resonance energy transfer (FRET) principle using 5-[(2'-aminoethyl)-amino] naphthelenesulfonic acid (EDANS) and 4-[[4-(dimethylamino) phenyl] azo] benzoic acid (Dabcyl) as the energy transfer pair, one fluorogenic substrate was designed for the evaluation of SARS-CoV 3CL(pro) proteolytic activity. RESULTS: The kinetic parameters of the fluorogenic substrate have been determined as Km=404 micromol.L(-1), kcat=1.08 min(-1), and kcat/Km=2.7 mmol(-1).L.min(-1). SARS-CoV 3CL(pro) showed substantial pH and temperature-triggered activity switches, and site-directed mutagenesis analysis of SARS-CoV 3CL(pro) revealed that substitutions of His41, Cys145, and His163 resulted in complete loss of enzymatic activity, while replacement of Met162 with Ala caused strongly increased activity. CONCLUSION: This present work has provided valuable information for understanding the catalytic mechanism of SARS-CoV 3CL(pro). This FRET-based assay might supply an ideal approach for the exploration SARS-CoV 3CL(pro) putative inhibitors.

Small envelope protein E of SARS: cloning, expression, purification, CD determination, and bioinformatics analysis.

AIM: To obtain the pure sample of SARS small envelope E protein (SARS E protein), study its properties and analyze its possible functions. METHODS: The plasmid of SARS E protein was constructed by the polymerase chain reaction (PCR), and the protein was expressed in the E coli strain. The secondary structure feature of the protein was determined by circular dichroism (CD) technique. The possible functions of this protein were annotated by bioinformatics methods, and its possible three-dimensional model was constructed by molecular modeling. RESULTS: The pure sample of SARS E protein was obtained. The secondary structure feature derived from CD determination is similar to that from the secondary structure prediction. Bioinformatics analysis indicated that the key residues of SARS E protein were much conserved compared to the E proteins of other coronaviruses. In particular, the primary amino acid sequence of SARS E protein is much more similar to that of murine hepatitis virus (MHV) and other mammal coronaviruses. The transmembrane (TM) segment of the SARS E protein is relatively more conserved in the whole protein than other regions. CONCLUSION: The success of expressing the SARS E protein is a good starting point for investigating the structure and functions of this protein and SARS coronavirus itself as well. The SARS E protein may fold in water solution in a similar way as it in membrane-water mixed environment. It is possible that beta-sheet I of the SARS E protein interacts with the membrane surface via hydrogen bonding, this beta-sheet may uncoil to a random structure in water solution.