Synthesis of Codon-optimized Human Interleukin-18 Gene by Combination of Chemical and Enzymatic Method

According to the amino acid sequence and codon preference of E. coli, the human interleukin-18（IL-18） gene was optimized to avoid the rare codons. The total length of the synthesized gene is 571 bp; 18 oligonucleotides, DNA fragments were designed and synthesized by the phosphoramidite four-step chemical method. The whole DNA sequence was synthesized by a one-step total gene synthesis method, and then inserted in pUC18 vector. Five positive clones identified by blue-white colony screening were sent to Shanghai Sangon Biological Engineering Technology and Service Co., Ltd. for sequencing. The sequencing result shows that one clone contained the complete correct gene in all the five positive clones.

Affinity Chromatography Purification of Recombinant Human Interleukin-6 from Its Fusion Protein with GST

Recombinant E.coli JM109, containing pHZ1818 plasmid which included the fused gene encoding human interleukin 6(IL 6), expressed a fusion protein with glutathion S transferase(GST). The fusion protein existed both in the supernatant and inside the bacterial cell,but the insoluble protein had no biological activity and could not be refolded. The rotative speed of the shaker and the temperature of induction were optimized to maximize the expression of the soluble fusion protein. From the supernatant of the cell sonicates Glutathion Sephrose 4B affinity column chromatography was employed to isolate the fusion protein which could be purified to >80 0 0 in a single step. The yield of soluble GST IL 6 was about 10 mg per liter culture. The GST was site specifically cloven by 6 hours of treatment with thrombin and from the thrombin digest mixture IL 6 was purified by Q high performance ion exchange chromatography. From 1 liter of E.coli culture 2 mg refined IL 6 was obtained. The purified IL 6 had a purity of more than 95 0 0 and a biological activity of 1.02×10 8 IU/mg.

CONSTRUCTION OF HUMAN INTERLUEKIN-18 DNA VACCINE AND IT'S EXPRESSION IN MAMMALIAN CELLS

Objective To construct the human interleukin 18 DNA plasmids vaccine and to express the eukaryotic plasmids vaccine in mammalian cell lines Cos 7 and D5.Methods Gene recombinant technique was used to construct hIL 18 eukaryotic expression vectors.Calcium phosphate method was performed to transect recombinant hIL 18 eukaryotic expression vectors into Cos 7 and D5 cells. In situ hybridization and Western Blot were implemented to verify the transient expression of recombinant hIL 18 in Cos 7 and D5.Results The eukaryotic expression plasmid pVAX1 IL 18 was constructed successfully.hIL 18 was transiently expressed in Cos 7 and D5.Conclusion The eukaryotic expression plasmid pVAX1 IL 18 was constructed. In situ hybridization and Western Blot results proved the successful transient expression of pVAX1 IL 18 in Cos 7 and D5.Therefore,the work has settled the foundation for further biological research on hIL 18,including immunogene therapy through hIL 18.

New Realms and New Highlights in the Legal Protection of Human Rights——Theoretical and Practical Innovations in the Legal Protection of Human Rights Since the 18th CPC National Congress

Since the 18th National Congress of the Communist Party of China （CPC）, the system for the legal protection of human rignts under socialism with Chinese characteristics has experienced innowtive development. In particular, the Decision on Certain Key Issues on Comprehensively Deepening Reform, which was adopted by the Third Plenary Session of the 18th CPC Central Committee, has made major reform arrangements related to the system and mechanisms for the legal protection of human rights under socialism with Chinese characteristics. Taking the theoretical and practical innovations since the 18th CPC National Congress in the protection of human rights as its perspective, this, article discusses new realms and new highlights in the legal protection of human rights.

Regulation of interleukin 33/ST2 signaling of human corneal epithelium in allergic diseases

AIM:To identify the function of ST2 and explore the role of IL-33/ST2 signaling in regulating the pro-allergic cytokine production in human corneal epithelial cells (HCECs). METHODS:Human corneal tissues and cultured primary HCECs were treated with IL-33 in different concentrations without or with different inhibitors to evaluate the expression, location and signaling pathways of ST2 in regulating production of pro-allergic cytokine and chemokine. The expression of mRNA was determined by reverse transcription and real time PCR, and protein production was measured by enzyme-linked immunosorbent assay (ELISA), immunohistochemical and immunofluorescent staining. ST2 protein was detected in donor corneal epithelium, and ST2 signal was enhanced by exposure to IL-33. ·RESULTS:IL-33 significantly stimulated production of pro-allergic cytokines thymic stromal lymphopoietin (TSLP) and chemokine (CCL2, CCL20, CCL22) in HCECs at both mRNA and protein levels. These stimulated productions of pro-allergic mediators by IL-33 were blocked by ST2 antibody or soluble ST2 protein(P 【0.05). Interestingly, the IκB-α inhibitor BAY11-7082 or NF-κB activation inhibitor quinazoline blocked NF-κB p65 protein nuclear translocation, and also suppressed the productions of these pro-allergic cytokines and chemokine induced by IL-33. CONCLUSION:These findings demonstrate that IL-33/ ST2 signaling plays an important role in regulating IL-33 induced pro-allergic responses. IL-33 and ST2 could become novel molecular targets for the intervention ofallergic diseases in ocular surface.

Relationship between interleukin 18 polymorphisms and susceptibility to chronic hepatitis B virus infection

AIM: To identify the relationship between the tagging single nucleotide polymorphism sites (tagSNPs) of the Interleukin-18 (IL-18) gene and genetic susceptibility to chronic hepatitis B virus infection in Chinese patients. METHODS: Five hundred and one cases of chronic hepatitis B virus (HBV) infection and 301 HBV natural clearance controls were studied. Two tagSNPs in the IL-18 gene (rs1946518A/C and rs574424C/G) were genotyped by the Multiplex Snapshot technique. The genotype and allele frequencies were calculated and analyzed. RESULTS: In the genotypes of rs1946518, the AA type was present at a higher frequency in the patients compared to those in the controls. Odds ratio (OR) of the AA genotype for the comparison with that of the AC and the CC genotype was 1.537 (95% confidence intervals (CI): 1.116-2.218, P = 0.009 < 0.025). In phenotypes, the allele C at rs1946518 was of a significantly lower frequency in the patients with chronic hepatitis B than that in the controls (P = 0.017 < 0.025). OR of the allele A for the comparison with that of the allele C was 1.279 (95% CI: 1.045-1.567). As for the rs574424 genotypes, no significant difference in this genotype distribution or in this allele frequency between the patients and the control subjects was observed. No significant difference in the haplotype frequencies between the patients with chronic hepatitis B and HBV natural clearance individuals was displayed. CONCLUSION: The data suggest that genotype AA and the allele A of the IL-18 at position rs1946518 are closely associated with the resistance to chronic hepatitis B and may be the dangerous gene. However, no statistical association was found between polymorphisms of rs574424 for IL-18 and hepatitis B.

18β-glycyrrhetinic Acid-induced Apoptosis and Relation with Intracellular Ca^2＋ Release in Human Breast Carcinoma Cells

Objective:To study the effects of 18β-glycyrrhetinic acid (GA) on proliferation inhibition, apop totic induction, and the relationship between GA-induced apoptosis and intracellular Ca2+ concentration in human breast carcinoma (MCF-7) cells. Methods: After MCF-7 cells were treated with GA at the concentrations from 50 μmol/L to 250 μmol/L for 24 h, cell viability of proliferation was assessed by MTT assay. After the cells were treated with 100 μmol/L, 150 μmol/L, and 200 μmol/L GA for 24 h, the rates of cell apoptosis were examined by terminal deoxynucleotide transferase mediated dUTP nick-end-labeling method and flow cytometry with Annexin V/propidium iodide fluorescent stain. After the cells treated with 150 μmol/L GA for 24 h, intracellular Ca2+ concentration was measured by Fure-2 fluorescein load method. Results: After the cells were treated with GA at the concentrations from 100 μmol/L to 250 μmol/L, the rates of proliferative inhibition were increased significantly (P<0.05 and P<0.01) in a dose dependent fashion. IC50 of the proliferation inhibition was 234.33 μmol/L. Treated with 100 μmol/L, 150 μmol/L, and 200 μmol/L, the rates of cell apoptosis were increased significantly (P<0.01). Intracellular Ca2+ concentration after treatment with GA was higher evidently than that of control (P<0.05). Conclusion: 18β-glycyrrhetinic acid has the effects of the proliferation inhibition and the apoptotic induction on MCF-7 cells. The rise of intracellular Ca2+ level may be depended on apoptosis induced by GA in MCF-7 cells.

Effect of glycyrrhizic acid and 18β-glycyrrhetinic acid on the differentiation of human umbilical cord-mesenchymal stem cells into hepatocytes

BACKGROUND End-stage liver disease is a global health complication with high prevalence and limited treatment options.Cell-based therapies using mesenchymal stem cells(MSCs)emerged as an alternative approach to support hepatic regeneration.In vitro preconditioning strategies have been employed to strengthen the regenerative and differentiation potential of MSCs towards hepatic lineage.Chemical compounds of the triterpene class;glycyrrhizic acid(GA)and 18β-glycyrrhetinic acid(GT)possess diverse therapeutic properties including hepatoprotection and anti-fibrosis characteristics.They are capable of modulating several signaling pathways that are crucial in hepatic regeneration.Preconditioning with hepato-protective triterpenes may stimulate MSC fate transition towards hepatocytes.AIM To explore the effect of GA and GT on hepatic differentiation of human umbilical cord-MSCs(hUC-MSCs).METHODS hUC-MSCs were isolated and characterized phenotypically by flow cytometry and immunocytochemistry for the expression of MSC-associated surface molecules.Isolated cells were treated with GA,GT,and their combination for 24 h and then analyzed at three time points;day 7,14,and 21.qRT-PCR was performed for the expression of hepatic genes.Expression of hepatic proteins was analyzed by immunocytochemistry at day 21.Periodic acid Schiff staining was performed to determine the functional ability of treated cells.RESULTS The fusiform-shaped morphology of MSCs in the treatment groups in comparison with the untreated control,eventually progressed towards the polygonal morphology of hepatocytes with the passage of time.The temporal transcriptional profile of preconditioned MSCs displayed significant expression of hepatic genes with increasing time of differentiation.Preconditioned cells showed positive expression of hepatocyte-specific proteins.The results were further corroborated by positive periodic acid Schiff staining,indicating the presence of glycogen in their cytoplasm.Moreover,bi-nucleated cells,which is the typical feature of hepatocytes,were also seen in the preconditioned cells.CONCLUSION Preconditioning with glycyrrhizic acid,18β-glycyrrhetinic acid and their combination,successfully differentiates hUC-MSCs into hepatic-like cells.These MSCs may serve as a better therapeutic option for degenerative liver diseases in future.

Study of recombinant human interleukin-12 for treatment of complications after radiotherapy for tumor patients

AIM To evaluate the treatment effects of recombinant human interleukin-12(rh IL-12) on radiotherapy complications, such as severe myelosuppression or pancytopenia, the decline or imbalance of immune function, etc.METHODS The patients received high-dose and short-course precise radiotherapy, such as Cyber knife and image-guided radiotherapy(IGRT), which can cause myelosuppression or pancytopenia and immune function decline within a short time. One-hundred subjects were enrolled in the study, and 50 were randomized to a treatment group which used rh IL-12 and 50 were randomized to a control group which used symptomatic and supportive therapy after radiotherapy. The 50 subjects in the treatment group were further divided into five subgroups and intervenedwith rh IL-12 at a dose of 50, 100, 150, 200 or 250 ng/kg respectively. The dose-effect relationship was observed. RESULTS Rh IL-12 significantly attenuated the decrease of peripheral blood cells in the treatment group, and immune function was improved after treatment. Due to the different radiation doses, there was a fluctuation within 12 h after treatment but mostly showing an increasing trend. As to the clinical manifestations, 2 patients in the 250 ng/kg subgroup showed low fever after administration, 1 patient in the 200 ng/kg subgroup and 2 patients in the 250 ng/kg subgroup showed mild impairment of liver function during the observation period.CONCLUSION Rh IL-12 has effective therapeutic and protective effects on complications following radiotherapy, such as the decline of blood cells, myelosuppression and the decline or imbalance of immune function, which indicated good prospects for development and application.

Multimodality functional imaging using DW-MRI and 18F-FDG-PET/CT during radiation therapy for human papillomavirus negative head and neck squamous cell carcinoma: Meixoeiro Hospital of Vigo Experience

AIMTo noninvasively investigate tumor cellularity measured using diffusion-weighted magnetic resonance imaging (DW-MRI) and glucose metabolism measured by 18F-labeled fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) during radiation therapy (RT) for human papillomavirus negative (HPV-) head and neck squamous cell carcinoma (HNSCC).METHODSIn this prospective study, 6 HPV- HNSCC patients underwent a total of 34 multimodality imaging examinations DW-MRI at 1.5 T Philips MRI scanner [(n = 24) pre-, during- (2-3 wk), and post-treatment (Tx), and 18F-FDG PET/CT pre- and post-Tx (n = 10)]. All patients received RT. Monoexponential modeling of the DW-MRI data yielded the imaging metric apparent diffusion coefficient (ADC) and the mean of standardized uptake value (SUV) was measured from 18F-FDG PET uptake. All patients had a clinical follow-up as the standard of care and survival status was documented at 1 year.RESULTSThere was a strong negative correlation between the mean of pretreatment ADC (ρ = -0.67, P = 0.01) and the pretreatment 18F-FDG PET SUV. The percentage (%) change in delta (∆) ADC for primary tumors and neck nodal metastases between pre- and Wk2-3 Tx were as follows: 75.4% and 61.6%, respectively, for the patient with no evidence of disease, 27.5% and 32.7%, respectively, for those patients who were alive with disease, and 26.9% and 7.31%, respectively, for those who were dead with disease.CONCLUSIONThese results are preliminary in nature and are indicative, and not definitive, trends rendered by the imaging metrics due to the small sample size of HPV- HNSCC patients in a Meixoeiro Hospital of Vigo Experience.

A preliminary study on the cloning and expression of human papiilomavirus type 18 E6 gene in Escherichia coli

We have cloned the E6 gene of human papillomavirus type 18 into anexpression plasmid pBD2.One of the recombinant plasmids (named pDV11) wasidentified by DNA analysis and protein product analysis.It could express a newprotein whose molecular weight correspods well with the expected one.Afterpurification,the expressed protein showed a positive result in countercurrentimmuno-electrophoresis with anti-β-gal serum and was proved to be the expectedβ-gal/E6 fusion protein.The physical map of pDV11 was also prepared.

Neuronal changes in the retinal ganglion cell layer following recombinant human interleukin-2 intravitreal injection in a rat model of chronically elevated intraocular pressure

Intraperitoneal injection of recombinant human interleukin-2（rhIL-2）inhibits neuronal apoptosis in the chronic ocular hypertension retinal ganglion cell layer.Intravitreous injection was performed on retinal ganglion cells in a Wistar rat model of chronically elevated intraocular pressure to observe the effects of LY294002 and AG490 on retinal ganglion cell survival,macrophage activation,and PI3K/Akt and JAK/STAT activation.The number of retinal ganglion cells in the rhIL-2 treatment group was much greater than in the normal control and phosphate-buffered saline groups.Western blot analysis revealed low Akt and STAT3 protein expression in the retina after 3-hour intravitreous injections of rhIL-2.However,protein expression was increased at 12 hours,but decreased again at 24 hours,with very low expression at 96 hours.LY294002 and AG490,which are inhibitors of the PI3K/Akt and JAK/STAT3 signal pathways,prevented upregulation of Akt and STAT3 protein expression in the retina,respectively.Intravitreous injection of rhIL-2 exhibited neuroprotective effects by decreasing retinal ganglion cell layer damage in a rat model of chronic glaucoma.These results suggest that intravitreal injection of rhIL-2 could induce the PI3K/Akt and JAK/STAT3 signaling pathways to protect retinal ganglion cells in chronically elevated intraocular pressure models.

Upregulation of stromal cell-derived factor-1 alpha/CXCR4 axis-induced migration of human neural progenitors by tumor necrosis factor-alpha and interleukin-8

BACKGROUND： Studies of several animal models of central nervous system diseases have shown that neural progenitor cells （NPCs） can migrate to injured tissues. Stromal cell-derived factor 1 alpha （SDF-la）, and its primary physiological receptor CXCR4, have been shown to contribute to this process. OBJECTIVE： To investigate migration efficacy of human NPCs toward a SDF-1α gradient, and the regulatory roles of tumor necrosis factor-α （TNF-α） and interleukin-8 （IL-8） in SDF-1α/CXCR4 axis-induced migration of NPCs. DESIGN, TIME AND SETTING： An in vitro, randomized, controlled, cellular and molecular biology study was performed at the Laboratory of Department of Cell Biology, Medical College of Soochow University between October 2005 and November 2007. MATERIALS： SDF-1α and mouse anti-human CXCR4 fusion antibody were purchased from R＆D Systems, USA. TNF-αwas purchased from Biomyx Technology, USA and IL-8 was kindly provided by the Biotechnology Research Institute of Soochow University. METHODS： NPCs isolated from forebrain tissue of 9 to 10-week-old human fetuses were cultured in vitro. The cells were incubated with 0, 20, and 40 ng/mL TNF-α, or 0, 20, and 40 ng/mL IL-8, for 48 hours prior to migration assay. For antibody-blocking experiments, cells were further pretreated with 0, 20, and 40 μg/mL mouse anti-human CXCR4 fusion antibody for 2 hours. Subsequently, the transwell assay and CXCR4 blockade experiments were performed to evaluate migration of human NPCs toward a SDF-1α gradient. Serum-free culture medium without SDF-1α served as the negative control. MAIN OUTCOME MEASURES： The transwell assay was performed to evaluate migration of human NPCs toward a SDF-1α gradient, which was blocked by fusion antibody against CXCR4. In addition, CXCR4 expression in human NPCs stimulated by TNF-α and IL-8 was measured by flow cytometry. RESULTS： Results from the transwell assay demonstrated that SDF-1α was a strong chemoattractant for human NPCs （P 〈 0.01）, and 20 ng/mL produced the highest levels of migration. Anti-human CXCR4 fusion antibody significantly blocked the chemotactic effect （P 〈 0.05）. Flow cytometry results showed that treatment with TNF-α and IL-8 resulted in increased CXCR4 expression and greater chemotaxis efficiency of NPCs towards SDF-1α（P 〈 0.01）. CONCLUSION： These results demonstrated that SDF-la significantly attracted NPCs in vitro, and neutralizing anti-CXCR4 antibody could block part of this chemotactic function. TNF-α and IL-8 increased chemotaxis efficiency of NPCs towards the SDF-1αgradient by upregulating CXCR4 expression in NPCs.

Contributions of the 18th CPC National Congress to Innovation and Development of Human Rights Theories

The report of the 18th National Congress of the Communist Party of China （CPC） set ＂respecting and ensuring human rights＂ as an important goal of development and reform in China, thus siniciz ing the latest Marxist human rights theories and reflecting major in novations and developments made by the CPC in the field of human rights theory. I. Human Rights as a Core Idea and Important Goal of Social Development Human rights are integral to the pursuit of the core value of socialism and to the core idea of socialism with Chinese characteristics. The report of the 18th CPC National Congress summarized the new progress and experience of human rights advance ment in recent years in China by setting ＂respecting and ensuring hu man rights＂ as an important goal of China as it completes the building of a moderately prosperous society.

China Society for Human Rights Studies Organizes Forum to Study and Implement Guidelines of 3rd Plenum of 18th CPC Central Committee

The China Society for Human Rights Studies （CSHRS） organized on Nov. 28 a forum to study and implement the guidelines of the third plenary session of the 18th Central Committee of the Communist Party of China （CPC）. Executive members of CSHRS and other CSHRS members in Beijing discussed improvement of judicial protection for human rights and legal construction in China. CSHRS President Luo Haocai, who was vice chairman of the 10th National Committee of the Chinese People＇s Political Consultative Conference, delivered a speech at the forum.

Safety and immunogenicity of human papillomavirus-16/18 AS04-adjuvanted vaccine in healthy Chinese females aged 15 to 45 years:a phase Ⅰ trial

Globally,about 70% of cervical cancers are associated with human papillomavirus (HPV)-16 or HPV-18 infection.A meta-analysis of epidemiologic studies in China showed that HPV was present in 98% of cervical cancer samples.The HPV-16/18 AS04-adjuvanted vaccine Cervarix has shown a high level of protection against HPV-16/18 infections and associated cervical lesions.This phase Ⅰ trial (NCT00549900) assessed the safety,tolerability,and immunogenicity of the vaccine in Chinese.Thirty healthy Chinese females,aged 15 to 45 years with a median age of 29.5 years,received three doses of Cervarix in Months 0,1,and 6.Safety was assessed via recording solicited local and systemic symptoms within 7 days and unsolicited symptoms within 30 days after each vaccination.Serious adverse events,new onset of chronic diseases,and other medically significant conditions were recorded throughout this trial.As an exploratory objective,HPV-16/18 antibody titers were determined by enzyme-linked immunosorbent assay in serum samples collected in Months 0 and 7.Pain at the injection site was the most frequently reported local symptom.Two subjects reported medically significant adverse events.Both cases were assessed as unrelated to vaccination by the investigator.In Month 7,100% seroconversion was observed for both anti-HPV-16 and anti-HPV-18 with high geometric mean antibody titers.HPV-16/18 AS04-adjuvanted vaccine,evaluated for the first time in Chinese females,was generally well tolerated and immunogenic,as previously shown in global studies.

The effect of interleukin-6 gene transfer on human cord blood megaka ryopoiesis

Objective:To investigate the effect of IL-6 gene transfe r into human cord blood hematopoietic stem cells on the production of megakaryocy t ic progenitors.Methods:IL-6 gene was transfected into human c o rd blood CD34+ cells using a retrovirus vector with the aid of recombinant fibro nectin fragments in the presence of a cocktail of cytokines (SCF,IL-6,sIL-6R,F L,and TPO).Colony-forming units-megakaryocyte (CFU-MK) assays were performed as IL-6 gene transduced CD34+ cells were incubated alone or in combination with I L -3 or sIL-6R, controlled with neoR gene transduced CD34+ cells.Result s :IL-6 alone or sIL-6R alone stimulated few CFU-MK colonies,the addit ion of sIL-6R to IL-6 gene transduced CD34+ cells significantly enhanced the prod uction of CFU-MK colonies.IL-6 gene transduced CD34+ cells showed a modest syn er gistic effect with IL-3.Conclusion:These results suggest that IL-6 gene transfer may protect patients from chemotherapy-induced thrombocytop en ia.

Protective effect of recombinant human IL-1Ra on CCl_4-induced acute liver injury in mice

AIM: To evaluate the effects of positive regulation of recombinant human interleukin 1 receptor antagonist (rhIL-1Ra) on hepatic tissue recovery in acute liver injury in mice induced by carbon tetrachloride (CCl 4 ). METHODS: Acute liver damage was induced by injecting 8-wk-old mice with CCl 4 1 mL/kg (1:3 dilution in corn oil) intraperitoneally (ip). Survival after liver failure was assessed by injecting 8-wk-old mice with a lethal dose of CCl 4 2.6 mL/kg (1:1 dilution in corn oil) ip. Mice were subcutaneously injected with 1 mg/kg recombinant human IL-1Ra twice a day after CCl 4 treatment for 5 d. Serum alanine amino transferase (ALT) and aspartate aminotransferase (AST) levels were determined with a commercial assay kit. Serum IL-1β, IL-1Ra levels were measured by enzyme-linked immunosorbent assay kit. Quantitative real-time polymerase chain reaction was used to determine liver IL-1β, IL-1Ra and IL-6 expression during CCl 4-induced acute liver injury. Liver sections were stained with hematoxylin-eosin. A histology-injury grading system was used to evaluate the degree of necrosis after acute liver injury. Proliferating cell nuclear antigen (PCNA) staining was used to evaluate the role of rhIL-1Ra in promoting hepatocyte proliferation. RESULTS: Quantitative analysis showed a higher level of IL-6 mRNA expression and reduced serum AST and ALT levels in the livers of the rhIL-1Ra-treated group at the early phase of CCl 4-induced acute liver injury. Histological examination indicated a decrease in centrilobular necrotic areas in mice treated with rhIL-1Ra, and a novel role of rhIL-1Ra in promoting hepatocyte proliferation was also supported by an increase of PCNA staining. All these results, accompanied by a strong survival benefit in rhIL-1Ra-treated vs PBS-treated groups, demonstrated that rhIL-1Ra administration ameliorated the histological damage and accelerated the regeneration and recovery process of the liver. CONCLUSION: rhIL-1Ra could be further developed as a novel therapeutic agent for the treatment of acute liver injury because of its ability to reduce hepatocellular damage and facilitate liver regeneration.

Epidermal growth factor receptor antibody plus recombinant human endostatin in treatment of hepatic metastases after remnant gastric cancer resection

We report a 55-year-old male who developed advanced hepatic metastasis and peritoneal carcinomatosis after resection of remnant gastric cancer resection 3 mo ago. The patient only received epidermal growth factor (EGF) receptor antibody (Cetuximab) plus recombinant human endostatin (Endostar). Anti-tumor activity was assessed by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computer tomography (PET/CT) at baseline and then every 4 wk. The case illustrates that 18FDG-PET/CT could make an early prediction of the response to Cetuximab plus Endostar in such clinical situations. 18FDG-PET/CT is a useful molecular imaging modality to evaluate the biological response advanced hepatic metastasis and peritoneal carcinomatosis to Cetuximab plus Endostar in patients after remnant gastric cancer resection.

Human Wharton’s jelly mesenchymal stem cells inhibit cytokine storm in acute respiratory distress syndrome in a rat model

Objective:To evaluate the potential effect of human Wharton’s jelly mesenchymal stem cells(hWJMSCs)on acute respiratory distress syndrome in lipopolysaccharide(LPS)-induced rats.Methods:The hWJMSCs(5×10^(4)/mL,5×10^(5)/mL,5×10^(6)/mL)were administered to rats on day 1 and day 8 after being induced by LPS(5 mg/kg body weight).TNF-αlevels in the lung and IL-18 and IL-1βlevels in the serum were measured using ELISA.In addition,caspase-1 expression in lung tissues was quantified using qRT-PCR,and NF-κB and IL-6 expressions were assessed using immunohistochemistry.Results:The hWJMSCs decreased TNF-αlevels in the lung and plasma IL-18 and IL-1βlevels.Moreover,the hWJMSCs downregulated the expressions of caspase-1,IL-6,and NF-κB in lung tissues.Conclusions:The hWJMSCs can decrease inflammatory markers of acute respiratory distress syndrome in a rat model and may be further investigated for the treatment of acute respiratory distress syndrome.