[Assessment of the burden of clonorchiasis and its temporal changes in China].

OBJECTIVE: To assess the burden of clonorchiasis and identify its temporal and spatial changes in China, thus to provide insights into the control and prevention of the diseases. METHODS: The disability-adjusted life years (DALYs) was employed as the primary indicator for the disease burden. The prevalence data of Clonorchis sinensis infection were obtainted from the three national surveys on important human parasitic diseases in China, conducting during the period from 1988 to 1922, from 2001 to 2004 and from 2014 to 2016, respectively, and the demographic data from National Bureau of Statistics of China. DALYs of clonorchiasis were calculated and the temporal changes were analyzed at both national and provincial levels, using the disability weight (DW) obtained from a community study in China. Sensitivity analysis was carried out to compare the resulted DALYs of China calculated under the method adopted in this study and that calculated with other commonly used methods. RESULTS: The national burden of clonorchiasis was 489174.04 [95% confidence interval (CI): (391648.87, 597509.87)] DALYs in China in 2016, indicating 0.36 [95% CI: (0.28, 0.43)] DALYs per 1 000 populations. The regions with a high burden of clonorchiasis were concentrated in southern China and northeastern China, and the provinces with the three highest burdens of clonorchiasis included Guangxi Zhuang Autonomous Region, Guangdong Province and Heilongjiang Province, which accounted for 91.18% of total burdens of clonorchiasis in China. During the periods of the three national surveys on important human parasitic diseases in China, the national burden of clonorchiasis was found to show a tendency of first rise and then decrease in China; however, the burden of clonorchiasis has recently shown a tendency towards a rise in Guangxi Zhuang Autonomous Region, Heilongjiang Province and Jiangxi Province. Sensitivity analysis showed that the calculation of diseases burden with age-stratified prevalence of clonorchiasis was similar to that of our method without age stratification; however, the burden estimates calculated only based on the DW of the severe symptoms were much lower than our estimates. CONCLUSIONS: The burden of clonorchiasis is high in China, with a large regional difference. Recently, the overall burden of clonorchiasis has shown a tendency of decline in China; however, there is a tendency towards a rise in some provinces. Therefore, the control of clonorchiasis requires more adaptations to local circumstances.

[Spatial and temporal characteristics of reported schistosomiasis cases in China based on a Bayesian interrupted time-series model].

OBJECTIVE: To investigate the spatial-temporal characteristics of reported schistosomiasis cases in China from 2004 to 2017, so as to provide insights into the development of different schistosomiasis control strategies at various stages. METHODS: The monthly data of reported schistosomiasis cases at a provincial level of China from 2004 to 2017 were collected from the Public Health Science Data Center, and the spatial-temporal distribution of reported schistosomiasis cases was preliminarily identified using a descriptive statistical method. According to the goals at different stages proposed by the National Mid- and Long-term Program for Schistosomiasis Prevention and Control in China (2004-2015), a Bayesian interrupted time-series model was established to analyze the provincial reported incidence, time trend and seasonal variations of schistosomiasis in China at different stages. RESULTS: The reported schistosomiasis cases were mainly concentrated in 5 provinces of Anhui, Jiangsu, Jiangxi, Hubei and Hunan and 2 provinces of Sichuan and Yunnan in China from 2004 to 2017, and the number of reported cases in endemic areas decreased gradually. The incidence of reported schistosomiasis cases predominantly peaked during the period from May to September in the marshland and lake regions, while no regular seasonality was seen in hilly regions. Bayesian interrupted time-series analysis showed the peak incidence of reported schistosomiasis cases in 4 provinces of Anhui, Hubei, Hunan and Jiangxi between May and September and in Jiangsu Province from July to November; however, no regular seasonal cycle was identified in hilly regions. The number of reported schistosomiasis cases showed a tendency towards an increase in 2 provinces of Hubei and Hunan from 2008 to 2014, with a minor peak during the period between March and April, and since 2015, the seasonality was not remarkable any longer in 3 provinces of Anhui, Jiangsu and Jiangxi with a decline in the incidence of reported schistosomiasis cases, while the seasonality remained in Hubei Province. CONCLUSIONS: The spatial-temporal characteristics of schistosomiasis in China, notably seasonality, vary at different control stages. Bayesian interrupted time-series model is effective to identify the spatial-temporal changes of schistosomiasis, and the schistosomiasis control strategy may be adjusted according to the spatial-temporal changes to improve the schistosomiasis control efficiency.

[Trends of female reproductive health status in Bangladesh from 1999 to 2018].

Objective: To analyze the changes of relevant indicators in reproductive health status among Bangladeshi women from 1999 to 2018 and to assess whether the 2030 Sustainable Development Goals (SDGs) can be achieved. Methods: Data were obtained from both the Bangladesh Demographic and Health as well as from the Maternal Mortality and Health Care Surveys. The trends of SDGs indicators related to reproductive health from 1999 to 2018 were analyzed and compared, and the average annual rate of change was calculated. Development index was used to assess the difficulty of achieving the SDGs. Results: The maternal mortality rate increased first and then leveled off from 2001 to 2016. From 1999 to 2018, the coverage of reproductive health care services and the proportion of women who had the right to make the decision on their own health care service, were generally increasing. Proportion of the following areas as: "contraceptive needs, women who consider that partner violence is justified, the rate of early marriage, and the rate of early childbearing etc.", were declining at various degrees. Development index of the antenatal care coverage, rate of delivery in medical facilities, percentage of live births attended by medically trained providers and the rate of postnatal care etc., were less than 1. The development indices of the maternal mortality rates were close to 1, while all the other indicators were greater than 1. Conclusions: The reproductive health-related SDGs indicators in Bangladesh appeared somehow degrees of progress from 1999 to 2018. However, for most indicators, the average annual rate of change was still lower than the expected to achieve the 2030 target which called for acceleration in the next few years.

C-Terminal Part of Glutamate-Ammonia-Ligase Adenyltransferase Gene Identified by RAPD-HRM with 3H Primer for E. Coli Screening.

A single random oligonucleotide 3H primer has been previously applied in random-amplified- polymorphic-DNA (RAPD)-PCR to distinguish stocked bacteria E. coli within a cocktail mixture also containing Enterococcus faecalis, Bifidobacterium longum and Ruminococcus gnavus. In this study, we demonstrate that a 702 base pair (bp) gene fragment can be amplified as a unique pattern by RAPD-PCR using a 3H primer in human faeces containing E. coli. This unique 702 bp amplicon contained a 687 bp gene fragment identified as the C-terminal region of the glutamate-ammonia-ligase adenyltransferase (glnE) gene of E. coli. By high-resolution melt (HRM) analysis, a mean melt-curve temperature of this 702 bp amplicon was determined to be approximately 88.1 ± 0.22 degrees Celsius (°C). A combination of RAPD with HRM in one single reaction based on this amplicon can achieve semi-quantitative detection of up to 102 CFU/ml of E. coli. To increase the signal intensity of HRM, a primer pair capable of screening E. coli directly from fresh human faeces was re-designed from the 687 bp gene segment, giving a mean peak melt-curve temperature at 88.35 ± 0.11 °C. Finally, single-nucleotide polymorphisms of this 687 bp gene segment were analysed for pathogenic E. coli strains, including UMN026, O83:H1, O104:H4, O157:H7 and O169:H41. We conclude that this 687 bp segment of the glnE gene has a high potential for screening of human faecal E. coli, including pathogenic strains, in contaminated food and water.

Lysine demethylase KDM2A inhibits TET2 to promote DNA methylation and silencing of tumor suppressor genes in breast cancer.

The coupling between DNA methylation and histone modification contributes to aberrant expression of oncogenes or tumor suppressor genes that leads to tumor development. Our previous study demonstrated that lysine demethylase 2A (KDM2A) functions as an oncogene in breast cancer by promoting cancer stemness and angiogenesis via activation of the Notch signaling. Here, we demonstrate that knockdown of KDM2A significantly increases the 5'-hydroxymethylcytosine (5'-hmc) level in genomic DNA and expression of tet-eleven translocation 2 (TET2) in various breast cancer cell lines. Conversely, ectopic expression of KDM2A inhibits TET2 expression in KDM2A-depleted cells suggesting TET2 is a transcriptional repression target of KDM2A. Our results show that KDM2A interacts with RelA to co-occupy at the TET2 gene promoter to repress transcription and depletion of RelA or KDM2A restores TET2 expression. Upregulation of TET2 in the KDM2A-depleted cells induces the re-activation of two TET downstream tumor suppressor genes, epithelial cell adhesion molecule (EpCAM) and E-cadherin, and inhibits migration and invasion. On the contrary, knockdown of TET2 in these cells decreases EpCAM and E-cadherin and increases cell invasiveness. More importantly, TET2 expression is negatively associated KDM2A in triple-negative breast tumor tissues, and its expression predicts a better survival. Taken together, we demonstrate for the first time that TET2 is a direct repression target of KDM2A and reveal a novel mechanism by which KDM2A promotes DNA methylation and breast cancer progression via the inhibition of a DNA demethylase.

Production and characterization of a monoclonal antibody against a late gene encoded by grouper iridovirus 64L.

Viral envelope proteins play important roles in viral infection and assembly. The grouper iridovirus ORF 64L (GIV-64L) was predicted to encode an envelope protein and was conserved in all sequenced Ranaviruses. In this study, the complete nucleotide sequence of the GIV-64L gene (1215 bp) was cloned into the isopropyl ß-D-1-thiogalactopyranoside (IPTG) induction prokaryotic expression vector pET23a. The approximately 50.2 kDa recombinant GIV-64L-His protein was induced, purified and used as an immunogen to immunize BALB/c mice. Three monoclonal antibodies (mAbs), all IgG1 class antibodies against GIV-64L protein, were produced by enzyme-linked immunosorbent assay. Reverse transcription polymerase chain reaction analyses revealed GIV-64L to be a late gene when expressed in grouper kidney cells during GIV infection with cycloheximide (an inhibitor of protein synthesis) or cytosine arabinoside (an inhibitor of DNA synthesis) present. Finally, one of the established mAbs, GIV-64L-mAb-17, was used in Western blotting and an immunofluorescence assay, which showed that GIV-64L protein was expressed at 24 h post-infection and localized only in the cytoplasm in GIV-infected cells, packed into a whole virus particle. The presently characterized GIV-64L mAbs should have widespread applications in GIV immunodiagnostics and other research, and these results should offer important insights into the pathogenesis of GIV.

Identification and characterization of a late gene of grouper iridovirus 61l and antibody production against the protein encoded by it.

In this study, a late gene encoded by grouper iridovirus, giv-61L, was identified and classified, and mouse monoclonal antibodies (mAbs) were raised against this protein. Giv-61L homologues were found only in the genus Ranavirus. Three mAbs to Giv-61L protein were produced. In drug inhibition assays, giv-61L was identified as a late gene. Finally, GIV-61L-mAb-8 was used in western blotting and immunofluorescence assays to demonstrate that Giv-61L protein was included in the GIV particle, expressed at 18 h, and localized only in the cytoplasm of GIV-infected cells. The results of this study provide insight into GIV pathogenesis and GIV-61L-mAbs will have broad applications in GIV immunodiagnostics.

The SUV39H1 inhibitor chaetocin induces differentiation and shows synergistic cytotoxicity with other epigenetic drugs in acute myeloid leukemia cells.

Epigenetic modifying enzymes have a crucial role in the pathogenesis of acute myeloid leukemia (AML). Methylation of lysine 9 on histone H3 by the methyltransferase G9a and SUV39H1 is associated with inhibition of tumor suppressor genes. We studied the effect of G9a and SUV39H1 inhibitors on viability and differentiation of AML cells and tested the cytotoxicity induced by combination of G9a and SUV39H1 inhibitors and various epigenetic drugs. The SUV39H1 inhibitor (chaetocin) and the G9a inhibitor (UNC0638) caused cell death in AML cells at high concentrations. However, only chaetocin-induced CD11b expression and differentiation of AML cells at non-cytotoxic concentration. HL-60 and KG-1a cells were more sensitive to chaetocin than U937 cells. Long-term incubation of chaetocin led to downregulation of SUV39H1 and reduction of H3K9 tri-methylation in HL-60 and KG-1a cells. Combination of chaetocin with suberoylanilide hydroxamic acid (SAHA, a histone deacetylase inhibitor) or JQ (a BET (bromodomain extra terminal) bromodomain inhibitor) showed synergistic cytotoxicity. Conversely, no synergism was found by combining chaetocin and UNC0638. More importantly, chaetocin-induced differentiation and combined cytotoxicity were also found in the primary cells of AML patients. Collectively, the SUV39H1 inhibitor chaetocin alone or in combination with other epigenetic drugs may be effective for the treatment of AML.

Development and characterization of two monoclonal antibodies against grouper iridovirus 55L and 97L proteins.

Grouper iridovirus (GIV) is one of the most important viral pathogens in grouper, particularly at the fry and fingerling stages. The study of GIV pathogenicity has been hampered by the lack of proper immunological reagents to study the expression and function of viral proteins in the infected cells. In this study, two mouse monoclonal antibodies (mAbs) against GIV 55L and 97L proteins were produced. Enzyme-linked immunosorbent assay (ELISA) and Western blotting were used to screen these hybridomas, resulting in the identification of two high-affinity mAbs named GIV55L-mAb-2 and GIV97L-mAb-3, respectively. Both mAbs belong to the IgG1 isotype and were effective in detecting their respective target viral protein. Reverse-transcription polymerase chain reaction (RT-PCR) and Western blot analyses of GIV-infected GK cells revealed that GIV 97L is an immediate early gene, whereas GIV 55L a late one. The localization of 55L and 97L in GIV-infected cells was further characterized by immunofluorescence microscopy with the mAbs. The 55L protein mainly aggregated in the cytoplasm while 97L distributed in both the nucleus and cytoplasm of the infected cells. These studies demonstrate the validity of the two mAbs as immunodiagnostic and research reagents.

Identification and characterization of a late gene encoded by grouper iridovirus 2L (GIV-2L).

Grouper iridovirus (GIV) belongs to the Ranavirus genus and is one of the most important viral pathogens in grouper, particularly at the fry and fingerling stages. In this study, we identified and characterized the GIV-2L gene, which encodes a protein of unknown function. GIV-2L is 1242 bp in length, with a predicted protein mass of 46.2 kDa. It displayed significant identity only with members of the Ranavirus and Iridovirus genera. We produced mouse monoclonal antibodies against the GIV-2L protein by immunizing mice with GIV-2L-His-tag recombinant protein. By inhibiting de novo protein and DNA synthesis in GIV-infected cells, we showed that GIV-2L was a late gene during the viral replication. Finally, immunofluorescence microscopy revealed that GIV-2L protein accumulated in both the nucleus and cytoplasm of infected cells. These results offer important insights into the pathogenesis of GIV.

Prediction of lymph node metastasis in T1/T2 tongue squamous cell carcinoma.

OBJECTIVES: In T1, T2, and clinically NO squamous cell carcinoma of the tongue, there is no reliable predictive variable to determine whether or not neck dissection is needed. Thus, we established a predictive score model based on tumour depth and other pathological variables. METHODS: We retrospectively reviewed 115 patients with T1 and T2 stage squamous cell carcinoma of the tongue. Their pathological variables were used to construct a score model for predicting the risk of cervical lymph node metastasis. RESULTS: A predictive score model was proposed using multivariate logistic regression analysis: Score = (2.694 x tumour depth (cm)) + (1.814 x lymphovascular invasion (yes = 1, no = 0)) + (1.175 x perineural invasion (yes = 1, no = 0)). The cutoff point was set at 2.7427. This predictive score model has a sensitivity of 91.2% and specificity of 65.4%. CONCLUSION: A predictive score model was built and a two-stage surgical approach was suggested for T1 and T2 squamous cell carcinoma of the tongue.

Establishment, characterization, virus susceptibility and transfection of cell lines from cobia, Rachycentron canadum (L.), brain and fin.

Establishment and characterization of two cobia, Rachycentron canadum, cell lines derived from cobia brain (CB) and cobia fin (CF) are described. Caudal fin and brain from juvenile cobia were dissociated for 30 and 10 min, respectively, in phosphate-buffered saline containing 0.25% trypsin at 25 degrees C. The optimal culture condition for both dissociated cells (primary cell culture) was at 28 degrees C in Leibovitz-15 medium containing 10% foetal bovine serum. The cells have been sub-cultured at a ratio of 1:2 for more than 160 passages over a period of 3 years. Origin of the cultured cells was verified by comparison of their sequences of mitochondrial cytochrome oxidase subunit I genes (cox I) with the cox 1 sequence from cobia muscle tissue. The cell lines showed polyploidy. No mycoplasma contamination was detected. Susceptibility to grouper iridovirus was observed for the CB cell line but not the CF cell line. Both cell lines expressed green fluorescent protein after being transfected with green fluorescent reporter gene driven by the cytomegalovirus promoter.

Caspase-dependent induction of apoptosis in barramundi, Lates calcarifer (Bloch), muscle cells by grouper iridovirus.

We recently reported that grouper iridovirus (GIV) can induce apoptosis in barramundi, Lates calcarifer, muscle (BM) and swim bladder (BSB) cell lines. In this paper, we further characterize the molecular mechanism underlying apoptotic death in BM cells triggered by GIV. DNA-laddering and apoptotic cells were observed in BM cells infected with UV-irradiated or untreated GIV but was absent in cells infected with heat-inactivated GIV, indicating the involvement of viral protein in the apoptosis event. In GIV-infected BM cells, the conversion of procaspase-3 to caspase-3 was evident and the level of caspase-8 and -9 increased as early as 30 min post-infection. When treated with a pancaspase inhibitor, the GIV-induced apoptosis event was abolished. These observations indicate that GIV-induced apoptosis is caspase-dependent, and that both the external and internal routes in the caspase-dependent pathway are likely involved in the apoptosis process.

Characterization of apoptosis induced by grouper iridovirus in two newly established cell lines from barramundi, Lates calcarifer (Bloch).

Two new cell lines have been established from the muscle and swim bladder tissues of barramundi, Lates calcarifer, and designated as BM (barramundi muscle) and BSB (barramundi swimbladder), respectively. The cells multiplied well at 28 degrees C in Leibovitz's L-15 medium supplemented with 10% foetal bovine serum, and have been continuously subcultured more than 100 times to date. Morphologically, BM cells were mostly fibroblastic, whereas BSB were mostly epithelial. Both cell lines were susceptible to grouper iridovirus (GIV) and displayed characteristics of apoptosis after viral infection. The induction of apoptosis was further assayed in GIV-infected BM and BSB cells by various methods. The inhibition of cell growth by GIV was demonstrated by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. Morphological observations revealed typical apoptotic features in the infected cells, including cell shrinkage and rounding, chromosome condensation and formation of apoptotic body-like vesicles. Chromosome fragmentation was detected by DNA laddering and TUNEL assays. Finally, the appearance of phosphotidylserine on the outer leaflet of apoptotic cell membranes was confirmed by annexin V staining. This is the first report of apoptosis induced by GIV in fish cells.

Mammary carcinoma with sebaceous differentiation in a dog.

This report describes an invasive mammary carcinoma with a rare distinctive feature characterized by sebaceous differentiation of tumor cells. This tumor occurred in a 10-year-old female mixed breed dog. The patient had two masses in the left fifth mammary gland. Grossly, the masses were firm, whitish to light brown, and superficially ulcerated. On cut surface, they were multilobulated with foci of necrosis. Microscopically, the tumors were composed of two distinctive neoplastic components, intraductal papillary adenocarcinoma and sebaceous carcinoma. The regions of sebaceous tumor were clumped separately, contained well-developed sebaceous cells and keratinized epithelial cells, and were surrounded by few to several layers of basaloid cells. The cells with abundant foamy cytoplasm that resembled sebaceous cells were also found within the intraductal papillary-like nests of mammary carcinoma, providing evidence of sebaceous metaplasia. Sebaceous differentiation in a mammary gland tumor is possible, because skin appendages and ductal apparatus of the mammary gland share a common anlagen. This tumor had an aggressive behavior with lymphatic metastasis. Consequentially, the dog had a poor prognosis.

Establishment of cell lines from a tropical grouper, Epinephelus awoara (Temminck & Schlegel), and their susceptibility to grouper irido- and nodaviruses.

Four tropical marine fish cell lines have been established from the eye, fin, heart and swim bladder of grouper, Epinephelus awoara (Temminck & Schlegel). Optimum media and temperature conditions for maximum growth were standardized. The eye and swim bladder cells were mostly epithelial, but the fin and heart cells were mostly fibroblastic. The viability of cells was 95% after 1 year of storage in liquid nitrogen (-196 degrees C). Besides these four cell lines, previously established grouper brain, kidney and liver cell lines were also used for a viral susceptibility study which showed that all the cell lines were sensitive to grouper iridovirus, whereas only brain, fin and liver cell lines were susceptible to the yellow grouper nervous necrosis virus (a nodavirus). Electron microscopy studies of the grouper irido- and nodaviruses in ultrathin sections of infected cells showed an abundance of viral particles in the cytoplasm of the virus-infected cells indicating the effective replication of these two viruses. It is suggested that these cell lines can be used for the isolation of putative fish specific viruses and provide a valuable tool to study the mechanisms of host-pathogen interactions. Furthermore, these cell lines upon transfection, using pEGFP-C1 and pEGFP-aMT2.5 (ayu metallothionein promoter), produced significant fluorescent signals indicating their utility for exogenous studies.

Ellagic acid inhibited 2-aminofluorene and p-aminobenzoic acid acetylation by mononuclear leucocytes from Sprague-Dawley rats.

Following exposure of rats to the arylamine carcinogen 2-aminofluorene, DNA-carcinogen adducts were found in the liver and bladder target tissues, and also in circulating leucocytes. This work investigated the effect of ellagic acid on arylamine (2-aminofluorene and p-aminobenzoic acid) acetylations in rat leucocytes. Evidence is presented that rat mononuclear leucocytes are capable of acetylating 2-aminofluorene and p-aminobenzoic acid. Both lymphocytes and monocytes were able to acetylate arylamines during 18 h of culture. Cultured lymphocytes produced about twice as much N-acetyl-2-aminofluorene from 2-aminofluorene and 2.2-fold as much N-acetyl-p-aminobenzoic acid from p-aminobenzoic acid as monocytes. After cotreatment with ellagic acid the lymphocyte and monocyte cultures indicated that ellagic acid reduced 2-aminofluorene acetylation.

Identification of cyprinol and cyprinol sulfate from grass carp bile and their toxic effects in rats.

To elucidate the responsible toxic components of grass carp bile, the bile salt 5 alpha-cyprinol sulfate and its desalted form 5 alpha-cyprinol from grass carp bile were purified and identified by analyses of infrared spectrum, (1)H-, (13)C-nuclear magnetic resonance spectra and mass spectrum. The toxicity of grass carp bile powder, butanol extract of grass carp bile powder, 5 alpha-cyprinol and 5 alpha-cyprinol sulfate in rats were further determined. The kidney and liver functions were significantly affected by grass carp bile powder, butanol extract and 5 alpha-cyprinol sulfate. However, 5 alpha-cyprinol also significantly affected the kidney function, but the toxic effect was less.

Staphylococcal enterotoxin A acts through nitric oxide synthase mechanisms in human peripheral blood mononuclear cells to stimulate synthesis of pyrogenic cytokines.

The pyrogenic response to supernatant fluids obtained from human peripheral blood mononuclear cells (PBMC) stimulated with staphylococcal enterotoxin A (SEA) was characteristic of a response to an endogenous pyrogen in that it was brief and monophasic and was destroyed by heating supernatant fluids at 70 degrees C for 30 min. The febrile responses were in parallel with the levels of interleukin-1 (IL-1), tumor necrosis factor (TNF), interferon-gamma (IFN-gamma), IL-2, and IL-6 in supernatant fluids obtained from PBMC treated with SEA. Both the pyrogenicity and the levels of IL-1, TNF, IFN-gamma, IL-2, and IL-6 in supernatant fluids started to rise at 6 to 18 h and reached their peak levels at 24 to 96 h after SEA incubation. Both the fever and the increased levels of IL-1, TNF, IFN-gamma, IL-2, and IL-6 in supernatant fluids obtained from the SEA-stimulated PBMC were decreased by incubating SEA-PBMC with anisomycin (a protein synthesis inhibitor), aminoguanidine (an inhibitor of inducible nitric oxide synthase [NOS]), or dexamethasone (an inhibitor of NOS). The febrile response to supernatant fluids obtained from the SEA-stimulated PBMC was attenuated by adding either anti-IL-1beta, anti-TNF-alpha, or anti-IFN-gamma monoclonal antibody (MAb) to supernatant fluids. The antipyretic effects exerted by anti-IL-1beta MAb were greater than those exerted by anti-TNF-alpha or anti-IFN-gamma MAb. The data suggest that SEA acts through the NOS mechanisms in PBMC to stimulate synthesis of pyrogenic cytokines (in particular, the IL-1beta).

Do the CK18 related proteins change in general in epithelial cancers?

The modulation of cytokeratin 18 during tumor transformation in hepatoma had been previously recognized through a series of biochemical and immunological approaches. Expression of cytokeratin 18 in transitional cell carcinoma comparing with hepatoma was investigated using the hepatoma transformation model. CK18 related molecules were found. In the present study, we design various epithelial cancers with the same model. CK18 related molecules were all evident. Therefore, we suggest that CK18 related proteins would play an important role in tumorigenesis of epithelial cancers.