[Guillain-Barre syndrome after allogeneic hematopoietic stem cell transplantation: a case report and literature review].

Guillain-Barre syndrome rarely develops after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and only a few reports exist in China. Guillain-Barre syndrome is an acute and life-threatening condition that requires early diagnosis and treatment. A patient with acute myeloid leukemia underwent allogeneic HSCT for >5 months and gradually developed limb muscle weakness and limited eye movement after coexisting with delayed acute intestinal graft-versus-host disease. After the examination of cerebrospinal fluid and electromyography, the diagnosis of Guillain-Barre syndrome was confirmed. After a high-dose intravenous immunoglobulin (IVIg) treatment, muscle strength gradually recovered, and the prognosis was good.

Robotic assisted partial nephrectomy reduces warm ischemia time and improves renal function acutely compared to the traditional laparoscopic approach; A single surgeon twin centre study.

Herein, we compared peri-operative and post-operative outcomes between robotic-assisted and laparoscopic partial nephrectomy. Various reviews of the current literature have detailed the lack of single-surgeon studies in this domain. Our study featured a single surgeon experienced in both approaches to reduce this bias seen in other multi-centre studies. We retrospectively analysed data from two hospitals to compare patient demographics, tumour characteristics, peri-operative and post-operative outcomes of all partial nephrectomies undertaken by a single surgeon with extensive experience in both approaches. Statistical analysis was carried out using GraphPad prism software. Warm ischaemia time was significantly reduced in the robotic arm compared to the laparoscopic group. This translated into an improvement in acute renal function. Length of stay was also significantly reduced. This study highlights some benefits of robotic-assisted in comparison to laparoscopic partial nephrectomy. Further large-scale prospective studies would be valuable in confirming these findings and justifying their usage against their financial cost.

[Comparison of three commercial photosensitizers for efficiency of inducing immunogenic cell death in anti-tumor immunotherapy].

OBJECTIVE: To compare 3 commercial immunogenic cell death (ICD) inducers, namely Chlorin e6 (Ce6), Neutral Red (NR), and Rose Bengal Sodium salt (RB), for their photosensitive properties, efficacy for photodynamic therapy (PDT) and ICD induction efficiency in antitumor immunotherapy. METHODS: Reactive oxygen species (ROS) probes were used to evaluate the photosensitivity of the 3 ICD inducers, and their capacity for inducing intracellular ROS production was evaluated using a DCFH-DA probe. The cytotoxicity and biocompatibility of the 3 photosensitizers were compared using a CCK-8 kit, and their ICD-inducing efficiency was assessed by detecting the levels of surface-exposed calreticulin (ecto-CRT), high mobility group protein 1 (HMGB1) and adenosine triphosphate (ATP). In the animal experiment, BALB/c mouse models bearing 4T1 cellderived subcutaneous tumor were given intratumoral injection of Ce6 or NR solution (30 µL, 5 mg/mL), followed 2 h later by white light irradiation for 10 min (400 mW/cm2). Body weight and tumor size changes of the mice were monitored, and the percentage of CD8+ T cells in the tumor and IFN-γ+ CD8+ T cells in the spleen were analyzed by flow cytometry 14 days after the treatment. HE and TUNEL staining was used to analyze tumor cell apoptosis in the mice. RESULTS: Among the 3 photosensitizers, Ce6 exhibited the strongest ROS-inducing capability and killing effect on the tumor cells. The results of ectoCRT, HMGB1 and ATP level detection all demonstrated a stronger ICD induction ability of Ce6. In the tumor-bearing mice, the tumor growth in Ce6 and NR groups was significantly inhibited after the treatment. The percentages of CD8+ T cells and IFN-γ+ CD8+ T cells were 12.7% and 7.1% in Ce6 group, respectively, significantly higher than those in NR group (6.1% and 2.8%, respectively; P < 0.05). HE and TUNEL staining revealed obvious tumor cell apoptosis in the tumor tissues in both Ce6 and NR groups, but the therapeutic effect was more prominent in Ce6 group. CONCLUSION: Among the 3 photosensitizers, Ce6 has the highest efficiency for inducing ROS production with the strongest PDT efficacy and ICD induction capability. Ce6 can also increase the number and function of CD8+ T cells in anti-tumor immunotherapy to initiate robust adaptive immune response.

[Mechanism of action of Jieduhuayu granules for remission of oxidative stress in hepatocytes].

Objective: To study and explore the effect and mechanism of action of Jieduhuayu granules on oxidative injury of human liver L02 cells. Methods: Human liver L02 oxidative injury model was established with 0.1 mmol/ L H(2)O(2) intervention for 1 h, and treated with different concentrations of Jieduhuayu (JDHY) solution. Hepatocytes were divided into five groups: normal, H(2)O(2), H(2)O(2) + JDHY (0.5 mg/ml), H(2)O(2) + JDHY (1 mg/ml), and H(2)O(2) + JDHY (1.5 mg/ml). MTT assay was used to detect hepatocytes activity. Transmission electron microscope was used to observe mitochondrial morphology in hepatocytes. Biochemical test was used to detect the levels of superoxide dismutase, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, malondialdehyde, and reduced glutathione and albumin in hepatocytes. Western blot was used to detect the expression levels of rabbit anti-phosphatidylinositol 3-kinase (PI3K), AKT and mTOR in hepatocytes. One-way analysis of variance was used for comparison between multiple groups, and the LSD method was used for pairwise comparison. Results: Compared with the normal group, the cell proliferation activity (P < 0.05), mitochondrial vacuolization, superoxide dismutase activity, reduced albumin and glutathione content, and PI3K, AKT, and mTOR protein expression levels in the H(2)O(2) group were all significantly reduced (P < 0.05), while the content of malondialdehyde and the activities of alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase were significantly increased (P < 0.05). Compared with H(2)O(2) group, the cell proliferation activity (P < 0.05), alterations in morphological remission of mitochondria, superoxide dismutase activity, reduced albumin and glutathione content, and PI3K, AKT and mTOR protein expression levels in the H(2)O(2) + JDHY (1 mg/ml) and H(2)O(2) + JDHY (1.5 mg/ml) group (P < 0.05) were all significantly increased (P < 0.05), while malondialdehyde content and alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities were significantly decreased (P < 0.05). Conclusion: Jieduhuayu granule can effectively improve oxidative stress and mitochondrial injury in hepatocytes, and its effect may be related to the promoting expression of PI3K/AKT/mTOR signaling pathways.

Analysis of the Incidence and Clinical Significance of Long and Short Corrected QT Interval in Electrocardiogram in Healthy Population of Changsha in China

ABSTRACT Objective: To analyse the incidence of long and short corrected QT (QTc) in a healthy sample of the population of Changsha in China. Methods: Standard 12-lead electrocardiograms (ECGs) were performed on 4025 subjects in Changsha of China, whose age ranged from 6 minutes after birth to 83 years, between January 1993 and December 2012. Heart rate and QT interval were measured and recorded. Corrected QT was calculated with Bazett´s formula (QTc = QT/RR0.5). All recruited individuals had taken healthy examination, ruling out general health issue, in The Second Xiangya Hospital of Central South University. Statistical analyses were performed using the SPSS 16.0 software (IBM Corp, Armonk, NY, USA). Results: The incidence of short QTc was 7.13% (287/4025 cases). The peak values of the incidence were in the 30-40 years group (15.71%). The low values were in the 1-3 months group and 3-6 months group (0%, 0.76%), respectively. The incidence of long QTc was 3.16% (127/4025 cases). The values diminished significantly after adulthood. The low values were in the age groups of 18-30 years (0.86%) and 30-40 years (0.71%), respectively. After the age of 50 years, the incidence of long QTc increased with age 50-60 years and 60-70 years and 70-83 years (7.89%, 9.06%, 14.06%), respectively. There was no statistically significant difference between the genders (p > 0.05). Conclusion: The peak incidences of long and short QTc existed in two separate age groups in the healthy sample. The peak incidence of short QTc was in the age group of 18-40 years, and the peak incidence of long QTc was in the age group beyond the 50 years. For these two age groups, it was recommended to pay close attention to the changes in their QTc in order to prevent cardiovascular events.

E2F1-induced upregulation of lncRNA HCG18 stimulates proliferation and migration in gastric cancer by binding to miR-197-3p.

OBJECTIVE: LncRNA HCG18 is considered to be an oncogene in many types of tumors. The aim of this study was to explore the role of lncRNA HCG18 in gastric cancer (GC). PATIENTS AND METHODS: HCG18 levels in GC tissues were detected. Potential biological influences of HCG18 on GC cell phenotypes were examined by Cell Counting Kit-8 (CCK-8), wound healing and transwell assay. Subsequently, bioinformatics analysis, Chromatin immunoprecipitation (ChIP), Luciferase assay and rescue experiments were conducted to identify the regulatory network of HCG18 in GC. RESULTS: It was found that HCG18 was upregulated in GC samples, and the knockdown of HCG18 inhibited proliferative and migratory abilities in GC. The transcription factor E2F1 could directly bind to the promoter region of HCG18 and thus activate its transcription. In addition, HCG18 sponged miR-197-3p to stimulate the malignant development of GC. CONCLUSIONS: HCG18 is upregulated in GC samples by E2F1 induction, which stimulates proliferative and migratory abilities in GC by binding to miR-197-3p.

Energy metabolism and mitochondrial defects in X-linked Charcot-Marie-Tooth (CMTX6) iPSC-derived motor neurons with the p.R158H PDK3 mutation.

Charcot-Marie-Tooth (CMT) is a group of inherited diseases clinically and genetically heterogenous, characterised by length dependent degeneration of axons of the peripheral nervous system. A missense mutation (p.R158H) in the pyruvate dehydrogenase kinase 3 gene (PDK3) has been identified as the genetic cause for an X-linked form of CMT (CMTX6) in two unrelated families. PDK3 is one of four PDK isoenzymes that regulate the activity of the pyruvate dehydrogenase complex (PDC). The balance between kinases (PDKs) and phosphatases (PDPs) determines the extend of oxidative decarboxylation of pyruvate to generate acetyl CoA, critically linking glycolysis and the energy producing Krebs cycle. We had shown the p.R158H mutation causes hyperactivity of PDK3 and CMTX6 fibroblasts show hyperphosphorylation of PDC, leading to reduced PDC activity and ATP production. In this manuscript we have generated induced pluripotent stem cells (iPSCs) by re-programming CMTX6 fibroblasts (iPSCCMTX6). We also have engineered an isogenic control (iPSCisogenic) and demonstrated that genetic correction of the p.R158H mutation reverses the CMTX6 phenotype. Patient-derived motor neurons (MNCMTX6) show increased phosphorylation of the PDC, energy metabolism defects and mitochondrial abnormalities, including reduced velocity of trafficking mitochondria in the affected axons. Treatment of the MNCMTX6 with a PDK inhibitor reverses PDC hyperphosphorylation and the associated functional deficits founds in the patient motor neurons, demonstrating that the MNCMTX6 and MNisogenic motor neurons provide an excellent neuronal system for compound screening approaches to identify drugs for the treatment of CMTX6.

An indel polymorphism in the 3' untranslated region of HMGB1 confers risk for hepatocellular carcinoma by regulating HMGB1 transcriptional activity in a Chinese population.

The present study aimed to assess the association of rs34000982 polymorphism located in the 3'untranslated region (3'UTR) of high mobility group box 1 (HMGB1) gene and the risk of hepatocellular carcinoma (HCC), and further to explore the underlying mechanism. Genomic DNA was extracted from peripheral blood of 320 patients with HCC and 360 matched controls. Rs34000982 polymorphism was genotyped by a polymerase chain reaction-polyacrylamide gel electrophoresis assay. The genotype-phenotype association of HMGB1 mRNA and protein expression in HCC tissues with different genotypes was detected by quantitative (q) PCR assay and western blot. Vectors containing the insertion (ins)/ins or deletion (del)/del genotype of the rs34000982 polymorphism were constructed and the HMGB1 transcriptional activity affected by the rs34000982 polymorphism was detected by the luciferase assay. It was identified that the ins/ins genotype of rs34000982 significantly increased the risk of HCC compared with the del/del genotype. Further the qPCR results demonstrated that the HMGB1 mRNA expression level in HCC tissues with ins/ins genotype was 2.24 times that of HCC tissues with ins/del and del/del genotypes and there was a similar trend at protein level. In addition, the insertion allele of rs34000982 disturbed the binding of miR-636 with the 3'UTR of HMGB1, thereby increasing HMGB1 transcriptional activity in vitro. These data suggest that the rs34000982 polymorphism may contribute to HCC susceptibility, in full or at least partially through the effect on HMGB1 transcriptional activity by disturbing the binding of miR-636 with the 3'UTR of HMGB1.

Cucurbitacin B inhibits cell proliferation and induces cell apoptosis in colorectal cancer by modulating methylation status of BTG3.

A previous report has revealed that cucurbitacin B (CuB) inhibits cancer cell proliferation and tumorigenesis in non-small cell lung cancer (NSCLC) through epigenetic modifications of several genes. However, whether CuB regulates cell proliferation and apoptosis by altering methylation status of BTG3 in colorectal cancer (CRC) remains unknown. In the present study, the results showed that BTG3 was downregulated in CRC tissues compared with adjacent normal tissues. CuB significantly increased BTG3 levels, induced promoter demethylation, and decreased the levels of DNA methyltransferases (DNMT1, DNMT3a and DNMT3b) in both CRC cell lines (SW480 and Caco-2), and the effects of CuB were comparable with those of 5-Aza-dC. We also found that CuB inhibited cell proliferation, accompanied with decreased expression of Ki67. Furthermore, CuB treatment induced cell cycle arrest at G1 phase in SW480 and Caco-2 cells, as well as decreased levels of Cyclin D1 and Cyclin E1. Incubation with CuB promoted cell apoptosis in both CRC cell lines in vitro, accompanied with elevation of cleaved caspase-3 and cleaved PARP. BTG3 knockdown abolished the effects of CuB in CRC cells. In summary, CuB-induced proliferation inhibition and cell apoptosis may be due to the reactivation of BTG3 by promoter demethylation. CuB may be a promising agent for CRC therapy.

[Analysis on probability of premature death and cause eliminated life expectancy of major non-communicable diseases in Chongqing Municipality, 2016].

Objective: To analyze the premature death probability and cause-eliminated life expectancy of cardiovascular disease, cancer, chronic respiratory disease and diabetes in Chongqing residents in 2016 so as to provide recommendation for non-communicable diseases (NCDs) prevention and control in Chongqing. Methods: Death cases of Chongqing Municipality between January 1(st) and December 31(st), 2016 were reported through death case registry system of national center for disease prevention and control. Death cases were sorted by international classification of disease (ICD-10). Mortality rate, standardized mortality rate, constituent ratio, premature death probability, life expectancy, and cause-eliminated life expectancy of four major NCDs were analyzed. Results: A total of 218 004 death cases were reported in Chongqing, 2016, and the mortality rate was 731.73/100 000. Of them, a total of 179 637 death cases of the four major NCDs including cardiovascular disease, cancer, chronic respiratory disease and diabetes were reported, accounting for 82.40% of all death cases. The mortality rate and standardized mortality rate of four major NCDs was 602.95/100 000 and 455.82/100 000, respectively. The premature death probability of four major NCDs was 15.96%, and males (25.39%) had a higher premature death probability than females (10.78%). The premature death probability of cardiovascular disease, cancer, chronic respiratory disease, and diabetes were 6.01%, 8.32%, 2.05%, and 0.43%, respectively. Life expectancy would increase by 6.02, 3.19, 1.89, and 0.19 years, after eliminating cardiovascular disease, cancer, chronic respiratory disease and diabetes respectively. Conclusion: The premature death probability of major NCDs was high in Chongqing, and males had a higher premature death probability than females did. Intervention and health management of the population should be conducted according to different gender-based risk factors to reduce the premature death probability.

Micropapillary bladder cancer: a clinico-pathological characterization and treatment analysis.

PURPOSE: Micropapillary bladder cancer (MPBC) is a very rare and aggressive variant of urothelial carcinoma (UC). The aim of this study was to investigate the clinico-pathological characteristics, treatment, and prognosis of MPBC to improve the understanding of this invasive disease. METHODS: We reviewed the records of 6 patients with MPBC who were evaluated and treated at our hospital between 2009 and 2015, and additionally reviewed 38 cases reported in the literature. RESULTS: In 44 cases, 36 cases (81.8%) were male and 8 cases (18.2%) were female, with a male:female ratio of 4.5:1; the median age of the patients was 68 years (range 45-91 years). A majority (81.8%) of patients with cT1 above or with lymph node and distant metastasis (cT2N0 in 18.2%, cT3-4N0 in 13.6%, cTanyN+ in 43.2%, and cTanyM+ in 6.8%). There was a high grade in 70.5% of patients. Lymphovascular invasion (LVI) was present in 61.4% of patients, and LVI in cT2 was more common than in cT1 (71.4 vs 22.2%). 52.3% of patients were treated with radical cystectomy (RC). After a mean follow-up of 16.2 months, 77.3% of patients developed distant metastases, and 47.7% of patients died of the disease. The mean overall survival (OS) was 28.9 months and the median OS was 20 months, and the amount of micropapillary (MPP) is correlated inversely with prognosis. CONCLUSIONS: Micropapillary bladder cancer is a rare variant of UC associated with a poor prognosis, which often presents at an advanced stage with LVI and distant metastases. The optimal treatment strategy is early RC combined with chemotherapy.

[IgG4-related lung disease: analysis of 8 cases and literature review].

Objective: To improve the understanding and treatment of IgG4-related lung disease (IgG4-RLD). Methods: The clinical characteristics, serum IgG4 levels, pathological features, chest CT, therapy and prognosis of 8 patients with IgG4-RLD were retrospectively analyzed. These patients were admitted to the People's Liberation Army General Hospital and the pathological diagnosis was made between December 2005 and March 2016. Relevant literatures were reviewed. Results: The 8 patients with IgG4-RLD included 4 men and 4 women, with an average age of (59±4) years (range, 37-74). The respiratory symptoms included shortness of breath, cough, and expectoration. Extra-pulmonary symptoms included abdominal pain, facial edema, and fever. Extrapulmonary organs were involved in 7 cases. Serum IgG4 levels were elevated in 8 cases, with an average concentration of(17±6)g/L. Chest CT showed solid lung nodules in 6, alveolar-interstitial infiltration in 5, bronchovascular lesions in 3 and ground glass shadows in 2 cases. PET/CT was performed in 2 cases and it showed multiple organ involvement with higher radioactivity uptake(SUVmax2.9-4.2). The pathological examination found lymphocyte and plasma cell infiltration in 7, fibrous tissue hyperplasia in 5, and occlusive vasculitis in 2 cases. On immunohistochemical staining, the ratio of IgG4-positive plasma cells to IgG-positive plasma cells was higher than 40%in 3 cases. The number of IgG4-positive plasma cells was 10-50/HP in 8 cases. The misdiagnosis rate was 100% before the final diagnosis was made. Three cases received glucocorticoids with immunosuppressant therapy, 2 received surgery combined with glucocorticoid therapy, 2 received glucocorticoid therapy alone, and 1 only received surgery. The follow-up time was 4-132 months, with remission in 7 cases, and disease progression in 1 case, but no death. A total of 195 cases of IgG4-RLD were reviewed from the literature, among whom 111 cases were admitted with respiratory symptoms, 144 with extra-pulmonary involvement. Serum IgG4 levels were detected in 179 cases, with an average concentration of 5.408 g/L. The nodular type was predominant, accounting for 36.9%. Of these cases, 178 received glucocorticoid treatment with disease remission. Conclusions: The major clinical manifestations of IgG4-RLD were shortness of breath, cough and expectoration. Multiple organ lesions were common. The misdiagnosis rate was extremely high. The diagnosis could be made based on pathological features and IgG4 serum levels . Glucocorticoid treatment was effective.

[Clinical significance of low-dose CT performed for three consecutive years in diagnosis of lung nodules in coal mine workers with 20 working years].

Objective: To investigate the clinical significance of low-dose CT (LDCT) in coal mine workers with relatively long working years. Methods: A total of 907 coal mine workers with ≥20 working years were enrolled, among whom there were 863 male and 44 female workers with a mean age of 49.5 years. Digital radiography (DR) was performed for these workers in 2013, and LDCT was performed for three consecutive years from 2014 to 2016. Results: A total of 32 workers were found to have lung nodules by DR in 2013, while in 2014, 269 workers were found to have non-calcified lung nodules by LDCT, and there was a significant difference in the number of workers with lung nodules (χ(2)=233.73, P<0.005) . There was also a significant difference in the detection rate of nodules between the workers with different working years of dust exposure (χ(2)=6.648, P=0.00) . The male workers had a significantly higher detection rate of nodules than the female workers (χ(2)=5.690, P=0.017) . There was no significant difference in the number of nodules between workers with different types of work (χ(2)=16.985, P=0.05) . There were 443 lung nodules in total, among which 71.56% were solid nodules and 55.75% had a size of ≤4mm; malignant nodules were confirmed by surgery in 6 (0.66%) of the 907 workers after baseline LDCT. LDCT reexamination in 2015 and 2016 found new nodules in 8 workers and enlarged nodules in 3 workers, and there was no significant change in the number of nodules with a size of ≤4 mm. Conclusions: It is necessary to perform high-risk population screening for coal mine workers by LDCT. The follow-up strategies for nodules with a size of ≤4mm are the same as those for negative results; annual reexamination is recommended for nodules with a size of >4-8 mm, and clinical treatment should be considered for nodules with a size of >8 mm.

Impact of Food Restriction on the Expression of the Adiponectin System and Genes in the Hypothalamic-Pituitary-Ovarian Axis of Pre-Pubertal Ewes.

Adiponectin, a cytokine secreted typically by adipocytes, has been implicated as a molecular switch between female reproduction and energy balance. The present study was undertaken to investigate the expression of adiponectin system and patterns of genes in the hypothalamic-pituitary-ovary (HPO) axis of food-restricted pre-pubertal ewes. Eighteen 2-month-old female ewes were assigned to 3 groups after a pre-feeding ad libitum for 10 days (six in each group): the control group (C), the low-food-restricted group (LR) and the high-food-restricted group (HR), which were fed with 100%, 70% and 50% of ad libitum food intake, respectively. The hypothalamus, pituitary, ovary and serum were collected after food restriction for 2 months. Results by ELISA showed that food restriction increased serum adiponectin concentrations. Quantitative real-time PCR showed that the gene transcriptions for adiponectin receptor 1 (AdipoR1) and 2 (AdipoR2) were enhanced in the hypothalamic-pituitary-ovarian (HPO) axis, while KISS-1/GPR-54 and gonadotropin-releasing hormone (GnRH) in the hypothalamus and luteinizing hormone ß-subunit (LHß) and follicle-stimulating hormone ß-subunit (FSHß) in the pituitary were reduced after food restriction. Immunohistochemistry results demonstrated that AdipoR1 localized in the oocytes of follicles in the ovary. These results suggest that the alterations in the expression of adiponectin and its receptors in response to food restriction might negatively influence the HPO axis.

B-cell translocation gene 3 overexpression inhibits proliferation and invasion of colorectal cancer SW480 cells via Wnt/ß-catenin signaling pathway.

Increasing evidences have shown that B-cell translocation gene 3 (BTG3) inhibits metastasis of multiple cancer cells. However, the role of BTG3 in colorectal cancer (CRC) and its possible mechanism have not yet been reported. In our study, we evaluated BTG3 expression in several CRC cell lines. Then, pcDNA3.1-BTG3 was transfected into SW480 cells. We found that BTG3 was upregulated in SW480 cells after overexpression plasmid transfection. BTG3 overexpression significantly inhibited cell growth and decreased PCNA (proliferating cell nuclear antigen) and Ki67 levels. BTG3 overexpression markedly downregulated Cyclin D1 and Cyclin E1 levels, whereas elevated p27. Overexpression of BTG3 arrested the cell cycle at G1 phase, which was abrogated by p27 silencing. Furthermore, migration, invasion and EMT of SW480 cells were significantly suppressed by BTG3 overexpression. Further investigations showed the inhibition of Wnt/ß-catenin signaling pathway. We then used GSK3ß specific inhibitor SB-216763 to activate the Wnt/ß-catenin signaling pathway. We found that Wnt/ß-catenin signaling pathway activation reversed the effect of BTG3 overexpression on cell proliferation, cell cycle progression, invasion and EMT. In conclusion, BTG3 overexpression inhibited cell growth, induced cell cycle arrest and suppressed the metastasis of SW480 cells via the Wnt/ß-catenin signaling pathway. BTG3 may be considered as a therapeutic target in CRC treatment.

MIF, secreted by human hepatic sinusoidal endothelial cells, promotes chemotaxis and outgrowth of colorectal cancer in liver prometastasis.

Growth and invasion of metastatic colorectal cancer (CRC) cells in the liver depend on microenvironment. Here, we showed that human hepatic sinusoidal endothelial cells (HHSECs) induce chemotaxis and outgrowth of CRC cells. Macrophage migration inhibitory factor (MIF), released by HHSECs, stimulated chemotaxis of CRC cells. MIF secreted by HHSECs, but not by CRC cells themselves, promoted migration and epithelial-mesenchymal transition (EMT) and facilitated proliferation and apoptotic resistance of CRC cells. In orthotopic implantation models in nude mice, exogenous MIF stimulated growth of CRC cells and metastasis. Furthermore, MIF accelerated mobility of CRC cells by suppressing F-actin depolymerization and phosphorylating cofilin. Noteworthy, MIF levels were correlated with the size of hepatic metastases. We suggest that HHSECs and paracrine MIF promote initial migration and proliferation of CRC cells in the hepatic sinusoids to generate liver metastases.

Evaluation of attenuated Salmonella choleraesuis-mediated inhibin recombinant DNA vaccine in rats.

DNA vaccination has been studied intensively as a potential vaccine technology. We evaluated the effect of an attenuated Salmonella choleraesuis-mediated inhibin DNA vaccine in rats. First, 15 rats were treated with different doses of an inhibin vaccine to evaluate vaccine safety. Next, 30 rats were divided into 3 groups and injected intramuscularly with the inhibin vaccine two (T1) or three times (T2) or with control bacteria (Con) at 4-week intervals. The inhibin antibody levels increased [positive/negative well (P/N) value: T1 vs Con = 2.39 ± 0.01 vs 1.08 ± 0.1; T2 vs Con = 2.36 ± 0.1 vs 1.08 ± 0.1, P < 0.05] at week 2 and were maintained at a high level in T1 and T2 until week 8, although a small decrease in T2 was observed at week 10. Rats in the T1 group showed more corpora lutea compared with the Con group (10.50 ± 0.87 vs 7.4 ± 0.51, P < 0.05). Estradiol (0.439 ± 0.052 vs 0.719 ± 0.063 ng/mL, P < 0.05) and progesterone (1.315 ± 0.2 vs 0.737 ± 0.11 ng/mL, P < 0.05) levels differed significantly at metestrus after week 10 between rats in the T1 and Con groups. However, there were no significant differences in body, ovary, uterus weights, or pathological signs in the ovaries after immunization, indicating that this vaccine is safe. In conclusion, the attenuated S. choleraesuis-mediated inhibin vaccine may be an alternative to naked inhibin plasmids for stimulating ovarian follicular development to increase the ovulation rate in rats.