Epidemiology, pathogenesis, immune evasion mechanism and vaccine development of porcine Deltacoronavirus.

Coronaviruses have been identified as pathogens of gastrointestinal and respiratory diseases in humans and various animal species. In recent years, the global spread of new coronaviruses has had profound influences for global public health and economies worldwide. As highly pathogenic zoonotic viruses, coronaviruses have become the focus of current research. Porcine Deltacoronavirus (PDCoV), an enterovirus belonging to the family of coronaviruses, has emerged on a global scale in the past decade and significantly influenced the swine industry. Moreover, PDCoV infects not only pigs but also other species, including humans, chickens and cattles, exhibiting a broad host tropism. This emphasizes the need for in-depth studies on coronaviruses to mitigate their potential threats. In this review, we provided a comprehensive summary of the current studies on PDCoV. We first reviewed the epidemiological investigations on the global prevalence and distribution of PDCoV. Then, we delved into the studies on the pathogenesis of PDCoV to understand the mechanisms how the virus impacts its hosts. Furthermore, we also presented some exploration studies on the immune evasion mechanisms of the virus to enhance the understanding of host-virus interactions. Despite current limitations in vaccine development for PDCoV, we highlighted the inhibitory effects observed with certain substances, which offers a potential direction for future research endeavors. In conclusion, this review summarized the scientific findings in epidemiology, pathogenesis, immune evasion mechanisms and vaccine development of PDCoV. The ongoing exploration of potential vaccine candidates and the insights gained from inhibitory substances have provided a solid foundation for future vaccine development to prevent and control diseases associated with PDCoV.

Recovery of iron from iron tailings by suspension magnetization roasting with biomass-derived pyrolytic gas.

A major industrial solid waste, iron tailings occupy a large area and pose long-term pollution risks. The pyrolysis gas of biomass was used as reducing agent to suspension magnetize and roast iron tailings to recover iron in this study. The process conditions, phase transformation and microstructure evolution of the iron tailings, pyrolysis gas production, and reaction regulations were investigated to explain the mechanism of iron recovery by suspension magnetization roasting (SMR) under the action of biomass pyrolysis gas. These studies were conducted using X-ray diffraction, scanning electron microscopy, vibrating sample magnetometer, thermo-gravimetric and differential scanning calorimetry, brunauer-emmett-teller specific surface area, and gas chromatography. The results showed that, after the grinding-magnetic separation process, the iron recovery rate was 93.32 %; the iron grade of the iron concentrate was 61.50 %. The optimal process conditions were determined as follows: fast pyrolysis temperature of 600 °C, SMR temperature of 700 °C, biomass dosage of 10 %, and SMR time of 4-5 min. The formation of Fe3O4 from the surface to the interior of the particles during the reduction process, and formation of pores and cracks led to an increase in the specific surface area. The SMR temperature not only improved the heat and mass transfer effect in the reduction process but also generated more CO and H2 through the reverse reaction of methanation, which work together to increase the saturation magnetisation of the unit sample. This method can be used to efficiently recover high quality iron from refractory iron ores.

Biomass waste as a clean reductant for iron recovery of iron tailings by magnetization roasting.

The magnetization roasting with coal as primary reductants adds cost and causes environmental pollution. Therefore, it is of great importance to investigate the biomass application as a reductant for magnetization roasting to recover iron from low-utilization iron tailings for emission mitigation and green utilization. This study systematically investigated the impact of biomass (pyrolysis gas from agricultural and forestry waste) as a reductant on the conversion of iron tailings to magnetite in magnetization roasting. Additionally, the thermal decomposition of biomass, phase transformation and microstructure evolution of iron tailings were analyzed by TG, XRD, BET, and other methods to elucidate the conversion mechanism for facilitating magnetized hematite in iron tailings with biomass-derived gas. The results showed that woody biomass was a more appropriate reductant for magnetization roasting; 650 °C was the optimal temperature for the complete transformation of hematite to magnetite by reduction roasting with biomass waste. Through magnetic separation, the concentrate with an iron grade of 62.04% and iron recovery of 95.29% was obtained, and the saturation magnetization was enhanced from 0.60 emu/g to 58.03 emu/g of iron tailings. During the magnetization roasting, CO and H2 generated from biomass reduced the hematite in tailings particles from interior to exterior, forming a loose structure with rich microfissures, facilitating the subsequent separation operations. This study offers a novel reference for applying biomass to exploit hematite minerals and shows the potential of biomass for energy savings and emission reduction in the utilization of iron tailing resources.

Biological Activities of Some Natural Compounds and Their Cytotoxicity Studies against Breast and Prostate Cancer Cell Lines and Anti-COVID19 Studies.

In this study, we investigated the inhibition effects of matairesinol, pregnanolone, hamamelitannin, secoisolariciresinol, and secoisolariciresinol diglicoside compounds on HMG-CoA reductase and urease enzymes. We have obtained results for the HMG-CoA reductase enzyme at the millimolar level, and for the urease enzyme at the micromolar level. Molecular docking calculations were made for their biological activities were compared. In docking calculations, proteins of experimentally used enzymes, activities of SARS-CoV-2 virus against RNA-dependent RNA polymerase (RdRp) protein, and anti-oxidant protein were compared. Then, ADME/T calculations were made to use the molecules as drugs. Cytotoxicity potential of these complexes against human breast and prostate cancers demonstrated that these compounds had good cytotoxic effects. There is growing attention to phenolic molecules and their presumed role in avoiding diverse degenerative diseases, such as cardiovascular and cancer diseases.

[The Mutated Gene Sequenced by NGS and the Correlation of Their Coexistent Mutual Exclusiveness in NPM1 Mutated Acute Myeloid Leukemia].

OBJECTIVE: To analyze the clinicobiological heterogeneity of NPM1 mutated (NPM1mut) acute myeloid leukemia (AML) detected by next generation sequencing (NGS) and their coexistence and mutual exclusivity relationship in the AML subtype. METHODS: The NGS data based on 112 genes related to blood disease in 238 newly diagnosed patients with NPM1mut were collected. The χ2 test and non-parametric test were used to analyze the distribution correlation between the genes in the mutational spectrum. RESULTS: Among all the patients, at least one co-mutation was detected out. The median number per case of the mutated genes, including NPM1mut was 4.5 (range 2－14), among them, there were 5.0 (range 2－10) for NPM1mut/FLT3-ITD+ and 4.0 (range 2－14) for NPM1mut/FLT3-ITD- cases, but it was no significant difference between the two groups (P=0.378). A total of 240 NPM1 mutational events were detected out in entire 238 NPM1mut patients, of which 10 (4.2%) were missense mutations, and were all found in NPM1mut/FLT3-ITD- patients. Most (9/10, 90%) of these NPM1 missense mutations were accompanied by AML subtype-defining cytogenetic or molecular abnormalities, of which 7 patients were in low risk or 2 in high risk. The most common NPM1mut coexisting mutations were DNMT3A (104, 43.7%), followed were FLT3-ITD (95, 39.9%) and FAT1 (57, 23.9%), FLT3-ITD and DNMT3A showed significant coexistence (P=0.005). FLT3-ITD showed significantly reciprocal exclusivity with FLT3-nonITD (P<0.001), NRAS (P<0.001), PTPN11 (P=0.017) and IDH1 (P=0.005), and showed an exclusivity inclination with KRAS (P=0.073). In addition, FLT3-nonITD along with KRAS (P=0.035), NRAS along with KRAS (P=0.008) and PTPN11 (P=0.039) coexisted significantly. CONCLUSION: Prognoses of AML involving less common NPM1 missense mutations should be stated on a case by case basis. The mutational landscape and co-occurrence and mutual exclusivity correlations of NPM1mut AML provide a mechanism explaining biological diversity and clinical heterogeneity in this AML subset.

Bioprotective and Functional Effect of Carnosine on Sepsis Induced Renal Damage in Male Albino Rat Model through Targeting IL-1ß and TNF-α Production.

Acute kidney injury (AKI), one of the frequently diagnosed and serious sepsis induced complication has high morbidity and mortality. The present study investigated the bioprotective and functional effect of carnosine on AKI induced pathological damage in Male Albino rat model in vivo. AKI in Albino rats was induced by cecal ligation and puncture surgery where as TNF-α and IL-1ß levels were detected using ELISA assay. Protein expression was examined by western blotting and pathological damage using hematoxylin and eosin (H&E). Treatment with carnosine suppressed AKI induced urea nitrogen and creatinine in Male Albino rat serum in dose-dependent manner. Development of sepsis mediated renal injury in Albino rats was also effectively prevented on treatment with carnosine. Secretion of AKI-induced IL-1ß, IL-18, and TNF-α in renal tissues was alleviated significantly in Albino rats by carnosine treatment. Additionally, in carnosine-treated Albino rats renal tissues AKI induced Bax expression was alleviated while as Bcl-2 was promoted compared to AKI Albino rats. Carnosine treatment improved the survival rate of the Albino rats with AKI. Carnosine inhibits renal tissue damage and increases survival rate in AKI Albino rat model. The mechanism involves alleviation of inflammatory cytokine secretion and promotion of Bcl-2 expression. Thus, carnosine may be used as a therapeutic agent for treatment of AKI.

Relationships between optical backscattering, particulate organic carbon, and phytoplankton carbon in the oligotrophic South China Sea basin.

The particulate backscattering coefficient (bbp) provides effective proxies for particulate organic carbon (POC) and phytoplankton carbon (Cphy); however, their bio-optical relationships in the oligotrophic ocean are rarely reported. In this work, based on the in-situ synchronous optical and biogeochemical measurements in the oligotrophic South China Sea (SCS) basin, we refined the regional relationships between POC (and Cphy) and bbp and investigated the impacts of phytoplankton community compositions and size classes on the bbp variability. The observations showed that: 1) POC and Cphy exhibited good linear relationships with bbp; 2) the relationship between Cphy and POC could also be fitted in a linear function with a positive POC intercept, and the POC contributed by phytoplankton-covarying non-algal particles was nearly two-fold of Cphy; and 3) the POC-specific bbp (b*bp) was positively correlated with the fraction of the phytoplankton groups haptophytes (Type 8) and diatoms to total Chla, but negatively correlated with the fraction of pico-phytoplankton to Chla (fpico). These findings suggest that in oligotrophic waters, the variability of b*bp was mainly determined by the variability in the relative contribution of large phytoplankton with complex structures.

Three-dimensional microspheric g-C3N4 coupled by Broussonetia papyrifera biochar: facile sodium alginate immobilization and excellent photocatalytic Cr(iv) reduction.

Photocatalysts comprising Broussonetia papyrifera biochar and g-C3N4 loaded on sodium alginate were prepared and characterized in terms of reusability and photocatalytic Cr(vi) reduction performance. The observed photocurrent responses as well as photoluminescence and UV-visible diffuse reflectance spectra showed that the best-performing catalyst featured the benefits of efficient photogenerated charge separation, superior electron conductance/transfer, and excellent light adsorption ability, which resulted in a higher photocatalytic Cr(vi) reduction performance compared to that of pure g-C3N4 powder. The prepared composite was shown to be reusable and well separable from the reaction mixture, thus being a promising material for the practical photocatalytic removal of Cr(vi) from wastewater. The trapping experiment and XPS spectra of catalysts after reactions confirm that the decontamination of Cr(vi) lies in the photocatalytic reduction of this species into low-toxicity Cr(iii) by photoinduced electrons generated from g-C3N4, followed by the adsorption of Cr(iii) on biochar or alginate with large specific areas.

Synergy of Photocatalysis and Adsorption for Simultaneous Removal of Hexavalent Chromium and Methylene Blue by g-C3N4/BiFeO3/Carbon Nanotubes Ternary Composites.

A novel graphite-phase carbon nitride (g-C3N4)/bismuth ferrite (BiFeO3)/carbon nanotubes (CNTs) ternary magnetic composite (CNBT) was prepared by a hydrothermal synthesis. Using this material, Cr(VI) and methylene blue (MB) were removed from wastewater through synergistic adsorption and photocatalysis. The effects of pH, time, and pollutant concentration on the photocatalytic performance of CNBT, as well as possible interactions between Cr(VI) and MB species were analyzed. The obtained results showed that CNTs could effectively reduce the recombination rate of electron-hole pairs during the photocatalytic reaction of the g-C3N4/BiFeO3 composite, thereby improving its photocatalytic performance, while the presence of MB increased the reduction rate of Cr(VI). After 5 h of the simultaneous adsorption and photocatalysis by CNBT, the removal rates of Cr(VI) and MB were 93% and 98%, respectively. This study provides a new theoretical basis and technical guidance for the combined application of photocatalysis and adsorption in the treatment of wastewaters containing mixed pollutants.

Biochar synthesized via pyrolysis of Broussonetia papyrifera leaves: mechanisms and potential applications for phosphate removal.

In this study, Broussonetia papyrifera leaves collected from land near a restored manganese mine in the Hunan Province of China were converted into biochar under high-temperature anaerobic conditions, regeneration and utilization of agricultural and forest waste, and applied to the prevention of eutrophication. The physicochemical properties of the B. papyrifera biochar were characterized using Micromeritics 3Flex analyzer, scanning electron microscope (SEM), Fourier transform infrared spectrometer (FT-IR), thermogravimetric analyzer (TGA), X-ray photoelectron spectrometer (XPS), zeta potential meter (zeta), and X-ray diffraction (XRD). The effects of pH, ionic strength, coexisting ions, time, initial concentration, and temperature on the decontamination process of phosphate in water were studied. The results indicated that adsorption was enhanced under alkaline conditions. The pseudo-second-order model of adsorption kinetics was applied to illustrate the adsorption processes. The chemical adsorption reaction was the main rate-limiting step in the adsorption process. Isotherm experimental data were best fitted by the Freundlich model at 25 °C and by the Langmuir model at 35 °C. The phosphate combined with B. papyrifera biochar mainly in the forms of exchangeable phosphorus (Ex-P), Al-bound phosphorus (Al-P), and Fe-bound phosphorus (Fe-P). These results indicate that B. papyrifera biochar is a suitable candidate for the treatment of a eutrophic body of water.

[Prognostic Significance of the Percentage of Blasts with CD34+/CD38low/-/CD123+ Phenotype in Acute Myeloid Leukemias].

OBJECTIVE: To investigate the percentage of blasts with the CD34+/CD38low/-/CD123+ phenotype in de novo acute myeloid leukemia (AML) patients and analyse its correlation with prognosis. METHODS: The percentage of CD34+/CD38low/-/CD123+ cells in the blast population of 148 newly diagnosed patients with AML was determined by using flow cytometry and its correlation with complete response, disease-free survival and overall survival were evaluated. RESULTS: The median percentage of CD34+/CD38low/-/CD123+ cells in newly diagnosed patients was 2.8% (ranged from 0.01 to 67%). The high expression of CD34+/CD38low/-/CD123+ in AML patients positively correlated with the NPM1 wild-type (χ2=5.194,P<0.05), but did not relate with the positive FLT3-ITD mutations (χ2=0.418,P>0.05). Further multivariable analysis showed that the higher expression of the CD34+/CD38low/-/CD123+ was associated with lower complete remission (P<0.05), worse disease-free survival(P<0.01) and shorter overall survival(P<0.01) in AML patients. CONCLUSION: The percentage of CD34+/CD38low/-/CD123+ cells at diagnosis significantly correlates with the response to treatment and survival. This prognostic marker may be used to rapidly identify the risk of treatment failure in clinical practice.

Decitabine enhances bortezomib treatment in RPMI 8226 multiple myeloma cells.

The present study investigated the interactions between decitabine (DAC) and bortezomib (BTZ) in RPMI 8226 multiple myeloma (MM) cells. Cells were exposed to DAC alone and in combination with BTZ for 48 h. A Cell Counting Kit­8 assay was performed to assess the rate of proliferation inhibition in the cells. Cell apoptosis was investigated by Annexin V-fluorescein isothiocyanate and propidium iodide staining. Flow cytometry was used to detect the different cell cycle stages. Western blotting was performed to analyze the protein expression levels of poly(ADP­ribose) polymerase 1 (PARP­1), caspase­3, ­9 and DNA (cytosine­5­)­methyltransferase 1 (DNMT1). Reverse transcription­quantitative polymerase chain reaction was used to assess DNMT1 gene expression. The combination of DAC and BTZ increased the proliferation inhibition, apoptotic rate and G0­G1 arrest compared with use of a single therapeutic agent. In addition, the combination treatment enhanced PARP­1 cleavage, caspase­3 and caspase­9 activation and downregulated the protein and mRNA expression levels of DNMT1. Therefore, the current study determined that the combination of BTZ and the epigenetic agent DAC may be a novel therapeutic strategy to improve the efficacy of BTZ in patients with MM.

Changes in expression of WT1 during induced differentiation of the acute myeloid leukemia cell lines by treatment with 5-aza-2'-deoxycytidine and all-trans retinoic acid.

The aim of the present study was to investigate the effect of 5-aza-2'-deoxycytidine (decitabine; DAC) and all-trans retinoic acid (ATRA) on Wilms' tumor 1 (WT1) in acute myeloid leukemia (AML) in vitro. The methylation status of the WT1 promoter was analyzed using methylation-specific polymerase chain reaction (MSP). The expression level of WT1 was detected by reverse transcription-quantitative polymerase chain reaction. The effect of DAC and ATRA on cell differentiation was evaluated by flow cytometry. The WT1 gene was methylated in U937 cells, but unmethylated in SHI-1 and K562 cells; the U937 cells did not express the WT1 gene, but the SHI-1 and K562 cells highly expressed the WT1 gene. DAC and ATRA, alone or in combination, exhibited no effect on the expression level of WT1 in the U937 cells and on the differentiation of the K562 cells. The combined treatment of DAC and ATRA markedly decreased the WT1 expression levels of the SHI-1 and K562 cells, and induced the differentiation of the SHI-1 and U937 cells. In the SHI-1 cells, WT1 expression changed inversely to the dynamic changes of cluster of differentiation 11b-positive rates. In conclusion, the combined treatment of DAC and ATRA has clinical therapeutic potential in acute monocytic leukemia patients with high WT1 expression and a poor response to standard induction chemotherapy.

Changes of Apolipoprotein M Gene Expression During the Cell Differentiation and Apoptosis Induced by Simvastatin in Combination with All-Trans Retinoic Acid in Human Promyelocytic Leukemia Cell Line NB4.

We examined the effect of simvastatin (SV) alone and in combination with all-trans retinoic acid (ATRA) on proliferation, differentiation, apoptosis and apolipoprotein M (apoM) expression in the human promyelocytic leukemia cell line NB4. The NB4 cells were incubated with 10 µM Simvastatin (10SV) and 0.5 µM ATRA alone or in combination, taking NB4 cells without any treatment as normal controls. The cells of different groups were collected at 24, 48 and 72 h post-incubation for further detection. Their morphological changes were observed after Wright stain. MTT method was used to assay the growth inhibition rate and flow cytometry to detect CD11b expression level and the early stage apoptosis ratio. Real-time quantitative reverse transcriptase-polymerase chain reaction was used to detect the apoM gene expression levels. As expected 0.5 µM ATRA did not affect proliferation or apoptosis, strongly induced differentiation and decreased apoM expression. 10SV inhibited proliferation, increased apoptosis, induced differentiation and increased apoM expression in a time-dependent manner. The addition of ATRA to SV did not increase the effect of SV on proliferation and apoptosis, but increased the effect of SV on differentiation. And completely abrogated the effect of SV on apoM expression. Together these results show that SV has anti-leukemic properties by itself and that combined therapy may have a place in the current anti-leukemic arsenal.

Overexpression of HOXA10 promotes gastric cancer cells proliferation and HOXA10(+)/CD44(+) is potential prognostic biomarker for gastric cancer.

Gastric cancer (GC) is a malignant cancer with poor prognosis. This study aims to investigate the roles of homeobox A10 (HOXA10) in GC and the correlations between HOXA10/CD44 expression and GC prognosis. Based on qRT-PCR and Western Blot analyses in 50 pairs of fresh GC samples and adjacent normal samples, it is identified that HOXA10 was significantly up-regulated in GC tissues at mRNA and protein levels. Cell proliferation, migration, and invasion were enhanced in GC cells with overexpressed HOXA10, while inhibited in cells with silenced HOXA10. Through IPA software, HOXA10 was predicted to interact with CD44 via MSN, which was preliminarily confirmed by using Western Blot. Through immunohistochemistry and tissue microarray (N=264), it is found that HOXA10 expression was significantly correlated with tumor size (P=0.011) and CD44 expression (P<0.001), while CD44 expression was significantly correlated with tumor size (P<0.001), depth of tumor invasion (P<0.001), lymph node metastasis (P<0.001), distant metastasis (P=0.001), UICC stage (P<0.001), histological differentiation (P<0.001), and HOXA10 expression (P<0.001). Additionally, the over-all survival and disease-free survival of HOXA10(+)/CD44(+) patients were dramatically decreased in comparison with that of HOXA10(+)/CD44(-), HOXA10(-)/CD44(+), or HOXA10(-)/CD44(-) patients (P<0.001), suggesting that the combinatory expression of HOXA10 and CD44 was correlated with poor GC prognosis. In conclusion, HOXA10 and CD44 might play roles in GC tumorigenesis, metastasis, and invasion. HOXA10(+)/CD44(+) expression might serve as a prognostic biomarker for GC, which needs more studies to validate.

Immunity of fungal infections alleviated graft reject in liver transplantation compared with non-fungus recipients.

OBJECTIVE: To evaluate of the immune tolerance in adult LT recipients with Invasive fungal infections (IFIs). METHODS: 109 consecutive LT recipients who received LT were included. Percentage of T subsets (CD4+CD25hiCD127- T cells, CD4+CD25loCD45RA+ T cells, CD4+CD25loCD45RA- and CD4+CD45RA-CD45RO+ T cells populations), levels of cytokines (IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IFN-γ, IL-12p70, IL-17, TNF-α, TNF-ß and GM-CSF) were detected by FACS and Bioplex in peripheral blood. Biopsy specimens were fixed, monoclonal antibodies against CD4, Foxp3 and IL-17 were applied to the above sections and FISH was performed. RESULTS: The risk of acute rejection was decreased in fungal infected liver transplant recipients comparing with non-fungal infected group. CD4+CD25hiCD127T cell population was increased in peripheral blood and memory CD4+CD45RA-CD45RO+ T cell population decreased. There was significant lower levels observed in naïve CD4+CD25loCD45RA+ and CD4+CD25loCD45RA- T cell populations in fungal infected liver transplant. Moreover, IL-2, IL-6, IL-10 and GM-CSF were decreased. However, no significant difference with IL-4 and IL-8 in serum in two infected LT recipients. CONCLUSION: The incidence of graft rejection in liver transplantation recipients with fungal infections was lower than the non-fungal group. It is important to assess the risk during pretransplant and postoperation for liver transplantation.

[MicroRNA-10a expression in FAB different subtype of acute myeloid leukemia and its relationship with drug resistance].

OBJECTIVE: This study was to investigate the expression of miR-10a in the different FAB subtype of acute myeloid leukemia (AML) and its relationship with drug resistance. METHODS: Forty de novo patients with AML, 16 patients with non-malignant hematologic disease and three AML cell lines HL-60, U937 and HL-60/ADR were enrolled in this study, the MiR-10a expression in bone marrow mononuclear cells of above-mentioned patients and 3 AML cell lines was detected by TaqMan RT-PCR. The correlation of miR-10a with clinicopathological factors of AML patients was analyzed. RESULTS: The miR-10a expression level in HL-60 cell line was higher than that in U937 cell line (P = 0.039). And its expression level in de novo AML patients was higher than that in patients with non-malignant hematologic disease (P < 0.01). FAB-AML-M3 patients exhibited higher expression of miR-10a than that in M1, M2 and M4 (P < 0.05); HL-60/ADR cell line showed higher miR-10a expression than that in HL-60 cell line (P < 0.01) . Except M3, the patients without CR (non-CR) after the first cycle of chemotherapy showed a higher level of miR-10a as compared with CR patients (P < 0.01). CONCLUSION: The high expression of miR-10a may be closely related to over-proliferation of promyelocyte and drug resistance of acute myeloid leukemia cells, except M3.

Overexpression of Reg4, alone or combined with MMP-7 overexpression, is predictive of poor prognosis in colorectal cancer.

Regenerating islet-derived family, member 4 (Reg4) is a secreted protein that plays a critical role in the development of colorectal cancer (CRC). In the present study, we examined the relationship between Reg4 and matrix metalloproteinase-7 (MMP-7) expression in CRC, particularly with regard to metastasis. RT-qPCR, western blotting, tissue microarray (TMA) and immunohistochemical staining were performed to detect Reg4 and MMP-7 expression in CRC tissues and paired adjacent normal tissues. As compared with normal tissues, most paired colon cancers showed a ≥2-fold increase in the Reg4 and MMP-7 mRNA levels, which was subsequently validated by the post-transcriptional levels. Immunohistochemical analysis demonstrated that Reg4 was associated with lymph node and distant metastasis, advanced American Joint Committee on Cancer (AJCC) stage, and histologic grade. Further studies showed the correlation between Reg4 and MMP-7 expression was significant in CRC with distant metastasis (r=0.555, P=0.021) and in the lymph­node metastasis samples (r=0.557, P<0.001). Patients with tumor positivity for the two molecules showed a worse prognosis even after radical surgery (P<0.001). Multivariate analysis revealed that patients with Reg4- and MMP-7-positive tumors had extremely poor OS (HR 4.63; 95% CI 2.43-8.81; P<0.001) and DFS (HR 3.88; 95% CI 2.08-7.22; P<0.001). Reg4 expression may be useful in the prediction of colon cancer prognosis when combined with MMP-7.

Retinoic acid receptor-ß gene reexpression and biological activity in SHI-1 cells after combined treatment with 5-aza-2'-deoxycytidine and all-trans retinoic acid.

BACKGROUND: This study was conducted to determine the antineoplastic activities of 5-aza-2'-deoxycytidine (decitabine; DAC) and all-trans retinoic acid (ATRA), administered either alone or in combination, on in vitro cultured SHI-1 cells as well as their effects on the expression of the tumor suppressor gene p16(INK4a) (p16) and the retinoic acid receptor (RAR)-ß. METHODS: Cell growth inhibition, differentiation and apoptosis were determined in SHI-1 cells treated with DAC and/or ATRA, and the combination index of the two compounds was calculated. Methylation of the p16 and RAR-ß genes in SHI-1 cells was detected by methylation-specific polymerase chain reaction (PCR). Real-time quantitative reverse transcriptase PCR was used to detect mRNA expression of the p16 and RAR-ß genes, and Western blot analysis was performed for protein expression. RESULTS: The drug combination had a synergistic effect on growth inhibition, differentiation and apoptosis of SHI-1 cells, and the effects of DAC and ATRA were dependent on time. DAC, either alone or in combination with ATRA, induced demethylation of the genes p16 and RAR-ß, whereas ATRA alone had no effect on methylation. The RAR-ß gene was reexpressed following DAC-ATRA combination treatment, and both agents had no effect on p16 expression. CONCLUSION: The results revealed that DAC used in combination with ATRA has significant clinical potential in the treatment of acute monocytic leukemia.

Overexpression of HOXB7 is associated with a poor prognosis in patients with gastric cancer.

Previous studies have indicated that the homeobox gene HOXB7 is overexpressed in certain cancers, which promotes tumorigenesis. However, less is known about the association between the HOXB7 gene and gastric cancer. The purpose of the present study was to investigate the association between the expression level of HOXB7 and gastric cancer. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to detect the expression of the homeobox B7 (HOXB7) RNA and protein, respectively. In addition, the association between the expression of HOXB7 and the clinicopathological characteristics of gastric cancer was analyzed by immunohistochemistry. The Kaplan-Meier method was used to calculate the survival rates, and the COX proportional hazards model was used to investigate univariate and multivariate analyses. The expression level of HOXB7 RNA and protein was significantly elevated in cancerous tissues compared with the corresponding normal mucosa. Increased expression of HOXB7 was significantly associated with tumor size (P=0.01), T stage (P<0.001) and advanced Union for International Cancer Control stage (P=0.003). In addition, patients with positive HOXB7 expression possessed an evident lower overall survival and disease-free survival rate compared with patients with tumors that did not express HOXB7. Furthermore, univariate and multivariate analyses indicated that HOXB7 served as a significant independent prognostic factor for OS and DFS in patients with gastric cancer. The present data indicate that the HOXB7 gene may play an important role in the process of gastric tumorigenesis, and also indicate that HOXB7 may be an important determinant of patient prognosis in gastric cancer.