Identification of Key Prognostic-Related miRNA-mRNA Pairs in the Progression of Endometrial Carcinoma.

OBJECTIVES: Endometrial carcinoma (EC) is one of the leading causes of death from gynecological cancer due to the high recurrence rate. However, the molecular mechanisms of EC progression are not well understood. This study aimed to identify critical genes and miRNAs associated with the progression and prognosis of EC and find the potential mRNA-miRNA regulatory relationship. DESIGN: The mRNA and miRNA data were downloaded from The Cancer Genome Atlas (TCGA) database. Next, differentially expressed genes (DEGs) were identified. Subsequently, prognosis-related genes and miRNAs were identified, followed by co-expression analysis of these mRNAs and miRNAs. Materials, Setting, and Methods: Samples in the mRNA microarray were divided into normal (n = 35), early stage (n = 385), and advanced stage (n = 153). Next, DEGs in normal versus early stage and early stage versus advanced stage were, respectively, identified, followed by Venn analysis to screen overlapping DEGs in 2 comparison groups. Based on the expression level of these DEGs, univariate Cox regression analysis and Kaplan-Meier method were performed to obtain prognosis-related genes. Moreover, genes-related miRNAs were predicted, and miRNA-mRNA co-expressed pairs were identified. Then, survival analysis of co-expressed miRNA was performed. Finally, co-expressed genes of key genes were identified, and then functional enrichment analysis was conducted. RESULTS: After integrating analysis, 326 overlapping (309 upregulated and 17 downregulated) DEGs were obtained. Univariate Cox regression analysis showed that 44 mRNAs and 8 miRNAs were associated with the prognosis of EC. Combined with the co-expressed analysis, only one prognosis-related hsa-miR-326/ELFN2 axis was obtained. In addition, functional enrichment analysis showed that co-expressed genes of ELFN2 were mainly involved in the PI3K-Akt signaling pathway. LIMITATIONS: These findings were obtained via bioinformatics analysis, and thus further experimental studies are urgently demanded to validate our results. CONCLUSIONS: One key miRNA-mRNA regulatory pair (hsa-miR-326-ELFN2) was screened. This study provided a bioinformatics basis for the molecular mechanism of EC progression and might contribute to the identification of novel therapeutic targets.

Identification of the association of CD28+ CD244+ Tc17/IFN-γ cells with chronic hepatitis C virus infection.

CD8+ T cells play multiple and complex immunological roles including antiviral, regulatory, and exhaustive effects in hepatitis C virus (HCV) infected patients. Some CD8+ T-cell subsets were confirmed to be closely related to HCV infection such as TCM , TEM , TEM RA, Tc17, and CD8+ Treg. Herein, we report a new subset of interleukin (IL)-17/interferon (IFN)-γ producing CD8+ T (Tc17/IFN-γ) cells that markedly correlate with CD28+ CD244+ cells, IL-17 levels, and HCV RNA in HCV patients. During early treatment with peg-IFN-a2a plus ribavirin, the imbalance of these Tc17/IFN-γ cells could be partially restored, together with normalized serum alanine aminotransferase but not aspartate transaminase. Also, we analyzed the dynamic change of the percentage of this T cells subset in patients with different outcome after 4-week course of treatment with peg-IFN-a2a plus ribavirin and found that the percentage of CD8+ CD28+ CD244+ T cells significantly decreased in recovered patients but not in nonrecovered patients. In vitro, CD28+ CD244+ T cells were the only CD8+ T-cell group that secreted both IL-17 and IFN-γ in this axis and blockade with anti-CD244 antibodies significantly reduced cytokine production. Taken together, this study demonstrates that the frequency and regulatory functions of CD28+ CD244+ Tc17/IFN-γ cells may play an important role in persistent HCV infection.

The Clinical Value of HSP60 in Digestive System Cancers: a Systematic Review and Meta-Analysis.

BACKGROUND: Heat shock protein 60 has been reported to have a high diagnostic value for digestive system cancers. We sought to systematically evaluate the diagnostic value of HSP60 in patients with gastric cancer (GC), colorectal cancer (CRC), and hepatocellular carcinoma (HCC). METHODS: Relevant literature was adopted from the online databases. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were pooled using random effects models. Summary receiver operating characteristic curve and the area under the curve (AUC) were used to express the overall test performance. Statistical analysis was performed by STATA 14.0 and Meta-DiSc 1.4 software. RESULTS: We merged 12 studies in a meta-analysis, including 1 GC, 5 CRC, and 6 HCC. Overall, the pooled sensitivity, specificity, and DOR to predict GC/CRC/HCC patients were 70%, 71%, and 8.49, respectively, corresponding to an AUC of 0.81. In subgroup analysis, the 82% specificity prompted a more advanced diagnostic accuracy for diagnosing CRC than HCC. CONCLUSIONS: HSP60 was an advanced biomarker for digestive system cancers and its abnormal expression might have implications for early diagnosis in screening of GC/CRC/HCC.

Detection Performance of Circulating MicroRNA-210 for Renal Cell Carcinoma: a Meta-Analysis.

BACKGROUND: Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney. miR-210 was a known oncogene with tumor-promoting effects in many types of cancer. This meta-analysis aimed to evaluate the potential diagnostic value of circulating miR-210. METHODS: Relevant literature was collected from PubMed and Embase. Sensitivity, specificity, and diagnostic odds ratio (DOR) for miR-210 in the diagnosis of RCC were pooled using random effects models. Summary receiver operating characteristic (SROC) curve analysis and the area under the curve (AUC) were used to estimate the overall test performance. RESULTS: This meta-analysis included seven studies with a total of 570 RCC patients and 415 healthy controls. For miR-210, the pooled sensitivity, specificity, and DOR to predict RCC patients were 0.74 (95% confidence interval [CI]: 0.70 - 0.77), 0.76 (95% CI: 0.71 - 0.80) and 8.81 (95% CI: 5.31 - 14.57), respectively. In addition, the AUC of miR-210 for the diagnosis of RCC is 0.81. CONCLUSIONS: MiR-210 might be a potential novel biomarker in the diagnosis of renal cell carcinoma.

Artificial human antigen-presenting cells are superior to dendritic cells at inducing cytotoxic T-cell responses.

Peptide recognition through the MHC class I molecule by cytotoxic T lymphocytes (CTLs) leads to the killing of cancer cells. A potential challenge for T-cell immunotherapy is that dendritic cells (DCs) are exposed to the MHC class I-peptide complex for an insufficient amount of time. To improve tumour antigen presentation to T cells and thereby initiate a more effective T-cell response, we generated artificial antigen-presenting cells (aAPCs) by incubating human immature DCs (imDCs) with poly(lactic-co-glycolic) acid nanoparticles (PLGA-NPs) encapsulating tumour antigenic peptides, followed by maturation with lipopolysaccharide. Tumour antigen-specific CTLs were then induced using either peptide-loaded mature DCs (mDCs) or aAPCs, and their activities were analysed using both ELISpot and cytotoxicity assays. We found that the aAPCs induced significantly stronger tumour antigen-specific CTL responses than the controls, which included both mDCs and aAPCs loaded with empty nanoparticles. Moreover, frozen CTLs that were generated by exposure to aAPCs retained the capability to eradicate HLA-A2-positive tumour antigen-bearing cancer cells. These results indicated that aAPCs are superior to DCs when inducing the CTL response because the former are capable of continuously presenting tumour antigens to T cells in a sustained manner. The development of aAPCs with PLGA-NPs encapsulating tumour antigenic peptides is a promising approach for the generation of effective CTL responses in vitro and warrants further assessments in clinical trials.

Spectrophotometric determination of silicon tetrahydride in the air of workplace.

A new, simple and sensitive method was developed for the determination of silicon tetrahydride in the air of workplace in this study. The alkaline resin-based spherical activated carbon was used to collect sample of silicon tetrahydride at workplace. Silicon tetrahydride was then desorbed from active carbon in 100°C hot water. After reacting with ammonium molybdate, oxalic acid and 1,2,4-trichlorobenzene alpha-naphthol amino sulfonic acid under acid condition, silicon tetrahydride was transformed into silicon molybdenum blue. The absorbance of silicon molybdenum blue was quantitatively measured at the wavelength of 680 nm. The results showed that the average sampling efficiency and desorption efficiency were 97.53% and 94.94%, respectively by this method. Detection limits were 0.054 µg/mL for the spectrophotometric method and 0.14 mg/m(3) for the determination of silicon tetrahydride in the air of workplace (sampling volume was 7.5 L). The conversion rate of silicon tetrahydride gradually decreased when storage time of samples was extended. The descent rate of sample was less than 10% when the sample was sealed for 7 days in the room temperature. It was concluded that this spectrophotometric method can be successfully used to determine silicon tetrahydride in the worksites.

Protein Dynamics Mediated by Cardiolipin in Bacteria.

Bacterial proteins targeting the appropriate subcellular sites are the base for their proper function. Several studies have shown that the anionic phospholipid cardiolipin (CL), a conical lipid preferring negative membrane curvature, modulates the lipid bilayers' structure, which impacts the activity of their resident proteins. Due to the favor of negative membrane curvature, CL is not randomly distributed in the bacterial plasma membrane. In contrast, it gathers in particular parts of the cell membrane to form microdomains, in which many functional membrane proteins are accumulated and carry out diverse physiological processes of bacteria, such as cell division, metabolism, infection, and antibiotic residence. In addition, CL has a unique structure that carries two negative charges, which makes it play a pivotal role in protein assembly, interaction, and location. These characteristics of CL make it closely related to many crucial physiological functions of bacteria. Here, we have reviewed the mechanism of protein dynamics mediated by CL initiated on the bacterial membrane. Furthermore, we studied the effect of CL on bacterial infection and antibiotic residence. Finally, the CL-targeting therapeutic agents for antibacterial therapy are also examined.

[Evaluation of transfection effectiveness using fluorescein-labelled oligonucleotides and entraster-R siRNA transfection into Plasmodium falciparum].

The cultured Plasmodium falciparum parasites were synchronized twice by 5% sorbitol treatment twice (8-hour window), and then incubated at 37 degrees C for 16 h. Parasites were transfected with fluorescein-labelled oligonucleotides (group A) or fluorescein-labelled oligonucleotides+Entranster-R siRNA transfection reagent (group B). After 5 h a part of parasites was evaluated by fluorescence microscopy and flow cytometry. The rest of parasites were washed with RPMI 1640 medium, and then incubated with 500 microl new medium containing 2% fresh erythrocytes for another 12 h, and detected by flow cytometry. The fluorescein-labelled oligonucleotides were localized in erythrocytes in group B, but nearly no fluorescence was observed for group A. Flow cytometry analysis indicated that the transfection efficiency of group B [(47.40 +/- 3.39)%] was higher than that of group A [(0.60 +/- 0.27)%]. In the second cell cycle, the transfection efficiency in group B was (26.85 +/- 2.90)%, while that of group A was nearly zero. The results indicated that Entranster-R siRNA transfection reagent may increase the oligonucleotides transfection efficiency.

Unraveling the enigma of tumor-associated macrophages: challenges, innovations, and the path to therapeutic breakthroughs.

Tumor-associated macrophages (TAMs) are integral to the tumor microenvironment (TME), influencing cancer progression significantly. Attracted by cancer cell signals, TAMs exhibit unparalleled adaptability, aligning with the dynamic tumor milieu. Their roles span from promoting tumor growth and angiogenesis to modulating metastasis. While substantial research has explored the fundamentals of TAMs, comprehending their adaptive behavior, and leveraging it for novel treatments remains challenging. This review delves into TAM polarization, metabolic shifts, and the complex orchestration of cytokines and chemokines determining their functions. We highlight the complexities of TAM-targeted research focusing on their adaptability and potential variability in therapeutic outcomes. Moreover, we discuss the synergy of integrating TAM-focused strategies with established cancer treatments, such as chemotherapy, and immunotherapy. Emphasis is laid on pioneering methods like TAM reprogramming for cancer immunotherapy and the adoption of single-cell technologies for precision intervention. This synthesis seeks to shed light on TAMs' multifaceted roles in cancer, pinpointing prospective pathways for transformative research and enhancing therapeutic modalities in oncology.

Malnutrition Predicts Adverse Outcomes After Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis.

BACKGROUND: Several studies have shown that malnutrition helps to predict the occurrence of adverse outcomes after transcatheter aortic valve replacement. However, there is still controversy and uncertainty regarding the prevalence and consequences of malnutrition. We performed a systematic review and meta-analysis to assess the relationship between malnutrition and poor postoperative outcomes in transcatheter aortic valve replacement. METHODS: Observational studies were searched in PubMed, EMBASE, Cochrane Library, Web of Science, and MEDLINE regarding the relationship between malnutrition and adverse outcomes after transcatheter aortic valve replacement, with the primary end-point being all-cause mortality and secondary outcomes such as cardiovascular complications and readmission rates. This meta-analysis was registered in PROSPERO (number CRD42022310139). RESULTS: A total of 10 studies involving 5936 subjects were included in the systematic review and meta-analysis. The results showed that malnourished patients had an increased risk of all-cause mortality after transcatheter aortic valve replacement compared with non-malnourished patients (hazard ratios [HR] = 1.32, 95% CI [1.13, 1.53], P <.01). Subgroup analysis showed that in Asia, postoperative all-cause mortality was significantly higher in malnourished transcatheter aortic valve replacement patients than in non-malnourished transcatheter aortic valve replacement patients (P <.01), and in addition, sample size and follow-up time may have contributed to the large heterogeneity. CONCLUSION: Malnutrition increases the risk of all-cause mortality in such patients and may predict the occurrence of adverse postoperative outcomes.

Knockdown of ABHD11­AS1 prevents the procession of TNBC by upregulating miR­199a­5p.

Breast cancer (BC) has become a threat to women's health. In addition, patients with triple-negative BC (TNBC) have the worst prognosis among all patients with BC. Furthermore, long non-coding RNA ABHD11-AS1 is aberrantly highly expressed in TNBC, suggesting that RNA ABHD11-AS1 may serve as an important role in the progression of TNBC. However, the detailed function of ABHD11-AS1 in TNBC remains largely unknown. The levels of ABHD11-AS1 in MDA-MB-231 cells were assessed by reverse transcription-quantitative PCR. To investigate the effect of ABHD11-AS1 on the progression of TNBC, a xenograft animal model was established. Knockdown of ABHD11-AS1 inhibited the epithelial-mesenchymal transition and migration of TNBC cells. In addition, ABHD11-AS1 promoted the viability and migration of TNBC cells by upregulating microRNA (miR)-199a-5p. Furthermore, knockdown of ABHD11-AS1 suppressed TNBC tumor growth in vivo by upregulating miR-199a-5p. In conclusion, knockdown of ABHD11-AS1 suppressed the progression of TNBC via upregulation of miR-199a-5p. The data of the present study may provide novel directions and a theoretical basis for TNBC treatment.

[Application of mind map in teaching of medical parasitology].

To improve the teaching quality of medical parasitology, mind map, a simple and effective learning method, was introduced. The mind map of each chapter was drawn by teacher and distributed to students before the class. It was helpful for teacher to straighten out the teaching idea, and for students to grasp the important learning points, perfect the class notes and improve learning efficiency. The divergent characteristics of mind map can also help to develop the students' innovation ability.

[Study of neutralization antibodie induced by DNA vaccine of HCV envelope protein 2 in mice].

OBJECTIVE: To explore the feasibility of induction of neutralization antibodies against hepatitis C virus (HCV) infection by HCV envelope 2 protein (E2) DNA vaccines immunization. METHODS: Two kinds of expression plasmids of HCV envelope 2 protein, plasmid pCI-1b661 Delta encoding hydrophobic carboxyl terminal truncated E2 and pCI-1b661 Delta encoding E2 with deletion of hypervariable region 1 (HVR1) and carboxyl terminal, were constructed and respectively transfeted 293T cells, and truncated E2 protein in whole cell lysate and supernatant of 293T cells were analyzed by Western blot. After BALB/c mouse were intramuscularly immunized by the plasmids, sera antibodies against HVR1 were detected by ELISA and the neutralization activity of the antibodies were assayed with HCV pseudotype particle (HCVpp). RESULTS: Both plasmids could express secretary truncated E2 protein. All the mice immunized with plasmid pCI-1b661 produced HVR1 antibodies,while no HVR1 antibodies were detected in pCI-1b661 Delta immunized mice. The sera neutralization percentages against HCVpp in pCI1lb661 Delta and pCI-lb661 Delta immunized mice were (78.5 +/- 13.8)% and (38.7 +/- 6.5)%, respectively (P <0.01). Sera neutralization activity against HCVpp was positive correlated with the level of HVR1 antibodies in pCI-1b661 immunized mice (r = 0.967, P<0.01). CONCLUSION: DNA vaccines expressing truncated E2 protein could induce neutralization antibodies against HCV, and neutralization antibodies mainly was consisted of the antibodies against HVR1.

Combined Treatment With H1 and H4 Receptor Antagonists Improves Th2 Inflammatory Responses in the Nasal Mucosa of Allergic Rhinitis Rats.

BACKGROUND: Histamine H1 receptor (H1R) antagonists are the first-line drugs for the treatment of allergic rhinitis (AR) at present. Emerging evidence supports an important role of histamine H4 receptor (H4R) in allergic diseases. However, information regarding the effects of combined treatment with H1 and H4 receptor antagonists in AR is limited. OBJECTIVES: We aimed to assess the effects of combined treatment with H1R and H4R antagonists on Th2 inflammatory responses in the nasal mucosa of AR rats. METHODS: Sprague Dawley rats were sensitized with ovalbumin and treated with H1R antagonist desloratadine or/and H4R antagonist JNJ7777120. Western blotting was used to assay the phenotypic markers of mature dendritic cells in the nasal mucosa, including major histocompatibility complex class II (MHC-II) and co-stimulatory molecules CD80, CD86 and OX40 ligand (OX40L). Th2 inflammatory cytokines including interleukin-4, 5 and 13 in nasal lavage fluids were determined by using enzyme-linked immunoassay. RESULTS: The treatment with desloratadine alone down-regulated the CD86 expression, and decreased the production of Th2 cytokines, but had no impact on the expression of MHC-II, CD80 and OX40L. The administration of NJ7777120 alone reduced the levels of CD86, OX40L and Th2 cytokines, whereas MHC-II and CD80 expression was unaffected. The combination of desloratadine and JNJ7777120 showed more significant synergistic therapeutic effects than monotherapy. CONCLUSION: H4R antagonist acted synergistically with H1R antagonist to reduce Th2 inflammatory responses by down-regulating CD86 and OX40L expression in the nasal mucosa of AR rats. The combination with H1R and H4R antagonists might be a new strategy for AR treatment.

Big Five Personality Model-based study of death coping self-efficacy in clinical nurses: A cross-sectional survey.

BACKGROUND: Specific personality traits may affect the ability of nurses to deal with patient death. The relationship between personality and death coping self-efficacy (DCS) has rarely been investigated in the palliative care setting. In this study, we explored the associations between different personality profiles and DCS in clinical nurses from general wards and ICU. METHODS: A cross-sectional survey of 572 Chinese nurses was conducted between August and September 2020, by way of a self-administered questionnaire. RESULTS: Among the Big Five Personality Traits, in nurses the score was highest for conscientiousness and lowest for neuroticism. With regard to DCS, nurses scored highly on the intention of hospice care. The Big Five Personality Traits were found to explain 20.2% of the overall variation in DCS. Openness, agreeableness and conscientiousness were significantly associated with DCS in nurses. CONCLUSIONS: Nursing managers should pay attention to differences in personality characteristics and provide personalized and targeted nursing education. This should improve nurses' DCS, enrich their professional development and promote high quality palliative care for patients and their families.

Hepatitis C virus F protein inhibits cell apoptosis by activation of intracellular NF-kappaB pathway.

AIM: To observe the influence of HCV F protein on apoptosis of HepG2 cells, and explore the association between F protein and NF-kappaB signal pathway. METHODS: HCV 1b F gene containing HepG2-F cells and HCV 1b C gene containing HepG2-C cells were treated with 100 IU/mL TNF-alpha, and analyzed by flow cytometry, Western blotting, and dual luciferase reporter assay. Empty plasmid pcDNA3.1(+) containing HepG2-3.1 cells were used as control. RESULTS: (i) With the treatment of TNF-alpha for 18 h, the apoptosis rates (AR) of HepG2-F and HepG2-3.1 cells were 0.41% (+/- 0.11%) and 37.43% (+/- 2.03%) respectively, while that of HepG2-C was 4.07% (+/- 0.18%). At 36 h after TNF-alpha treatment, the AR of HepG2-F and HepG2-3.1 cells were 10.03% (+/- 0.41%) and 44.63% (+/- 3.37%), and that of HepG2-C was 14.95% (+/- 0.85%). (ii) After the treatment of TNF-alpha for 0.5-18 h, the p65 contents in the whole cells of HepG2-F and HepG2-3.1 showed no significant difference (P = 0.34, t = 1.08), while the p65 contents in the nucleus of HepG2-F and HepG2-3.1 cells were 3.8-1.9 times and 1.8-1.0 times higher than that in the non-treated cells (P = 0.013, t = 4.25). (iii) The relative luciferase unit (RLU) of the HepG2 cells, co-transfected with pcDNA3.1-F and pNF-kappaB-luc, and then treated with TNF-alpha (100 IU/mL) for 18 h, showed a pcDNA3.1-F dose-dependent increase. CONCLUSION: HCV F protein can over-activate NF-kappaB signal pathway, which makes HepG2-F cells able to resist TNF-alpha induced apoptosis.

Genome-Wide Screening and Functional Analysis Identifies Tumor Suppressor Long Noncoding RNAs Epigenetically Silenced in Hepatocellular Carcinoma.

Long noncoding RNAs (lncRNA) play critical roles in the development of cancer, including hepatocellular carcinoma (HCC). However, the mechanisms underlying their deregulation remain largely unexplored. In this study, we report that two lncRNAs frequently downregulated in HCC function as tumor suppressors and are epigenetically silenced by histone methyltransferase EZH2. lncRNAs TCAM1P-004 and RP11-598D14.1 were inhibited by EZH-mediated trimethylation of H3K27me3 at their promoters. Downregulation of TCAM1P-004 and RP11-598D14.1 was frequently observed in HCC tumors compared with adjacent normal tissues. Both lncRNAs inhibited cell growth, cell survival, and transformation in HCC cells in vitro as well as tumor formation in vivo. Using RNA pull-down and mass spectrometry, we demonstrated that TCAM1P-004 bound IGF2BP1 and HIST1H1C, whereas RP11-598D14.1 bound IGF2BP1 and STAU1. These lncRNA-protein interactions were critical in regulating p53, MAPK, and HIF1α pathways that promoted cell proliferation in HCC. Overexpression of EZH2 was critical in repressing TCAM1P-004 and RP11-598D14.1, and EZH2-TCAM1P-004/RP11-598D14.1-regulated pathways were prevalent in human HCC. Aberrant suppression of TCAM1P-004 and RP11-598D14.1 led to loss of their tumor-suppressive effects by disrupting the interaction with IGF2BP1, HIST1H1C, and STAU1, which in turn promoted HCC development and progression. Collectively, these findings demonstrate the role of TCAMP1P-004 and RP11-598D14.1 in suppressing tumor growth and suggest that EZH2 may serve as a therapeutic target in HCC. SIGNIFICANCE: EZH2-mediated loss of lncRNAs TCAM1P-004 and RP11-598D14.1 hinders the formation of tumor suppressor lncRNA-protein complexes and subsequently promotes HCC growth.

Activation of CD3+ T cells by Helicobacter pylori DNA vaccines in potential immunotherapy of gastric carcinoma.

Most of gastric carcinoma (GC) is attributed to infection by Helicobacter pylori (H. pylori) but there is increasing evidence that the positive H. pylori status correlates with better prognosis in GC. The H. pylori-induced cellular immune response may suppress cancer and in this work, recombinant pcDNA3 plasmids encoding various fragments of H. pylori virulence genes of cagA, vacA and babA are constructed and combined into groups to immunize BALB/c mice. The activated splenic CD3+ T cells are purified and the anticancer effects are investigated in vitro and in vivo. The H. pylori DNA vaccines induce a shift in the response from Th1 to Th2 that mimicks the immune status in patients of GC with chronic H. pylori infection. The stimulated CD3+ T cells inhibit the growth of human GC cells in vitro and adoptive transfusions of the CD3+ T cells suppress the growth of GC xenograft in vivo. The effects may be caused by the larger ratios of infiltrated CD8+/CD4+ T cells, reduced infiltration of regulatory FOXP3+ T cells, and enhanced apoptosis induced by upregulation of Caspase-9/Caspase-3 and downregulation of Survivin. Our results reveal the potential immunotherapeutic value of H. pylori vaccine-activated CD3+ T cells in those with advanced GC.

Hepatitis C virus F protein up-regulates c-myc and down-regulates p53 in human hepatoma HepG2 cells.

OBJECTIVES: Hepatitis C virus (HCV) F protein is a newly identified protein encoded by an alternative open reading frame that +1 overlaps core-encoding gene. It has been found that regulation of c-myc and p53 genes by HCV core protein is involved in liver cancer genesis. We wondered whether HCV F protein exerts similar or adverse regulatory effects on the transcription of c-myc and p53 genes. METHODS: HCV F gene-containing, plasmid pcDNA3.1-F and HCV core gene-containing pcDNA3.1-C were constructed and transiently transfected into HepG(2) cells. Real-time quantitative PCR or Western blotting was used to determine the changes at transcription or translation levels of c-myc and p53 genes. RESULTS: The transcription level of c-myc was much higher in pcDNA3.1-F transfected cells than those without plasmid transfected. Whereas the level of p53 transcription in pcDNA3.1-F transfected cells was lower than those in the parental cells. Moreover, levels of c-myc expression were up-regulated and those of p53 expression were down-regulated by HCV F protein. CONCLUSIONS: HCV F protein is of regulatory properties in cellular oncogene c-myc and anti-oncogene p53, which may be implicated in the formation of hepatocellular carcinoma.

Transcriptomic Analysis Reveals Genes Mediating Salt Tolerance through Calcineurin/CchA-Independent Signaling in Aspergillus nidulans.

Adaptation to changes in the environment is crucial for the viability of all organisms. Although the importance of calcineurin in the stress response has been highlighted in filamentous fungi, little is known about the involvement of ion-responsive genes and pathways in conferring salt tolerance without calcium signaling. In this study, high-throughput RNA-seq was used to investigate salt stress-induced genes in the parent, ΔcnaB, and ΔcnaBΔcchA strains of Aspergillus nidulans, which differ greatly in salt adaption. In total, 2,884 differentially expressed genes including 1,382 up- and 1,502 downregulated genes were identified. Secondary transporters, which were upregulated to a greater extent in ΔcnaBΔcchA than in the parent or ΔcnaB strains, are likely to play important roles in response to salt stress. Furthermore, 36 genes were exclusively upregulated in the ΔcnaBΔcchA under salt stress. Functional analysis of differentially expressed genes revealed that genes involved in transport, heat shock protein binding, and cell division processes were exclusively activated in ΔcnaBΔcchA. Overall, our findings reveal that secondary transporters and stress-responsive genes may play crucial roles in salt tolerance to bypass the requirement for the CchA-calcineurin pathway, contributing to a deeper understanding of the mechanisms that influence fungal salt stress adaption in Aspergillus.