Depletion of DNMT3A Suppressed Cell Proliferation and Restored PTEN in Hepatocellular Carcinoma Cell

Promoter hypermethylation mediated by DNA methyltransferases (DNMTs) is the main reason for epigenetic inactivation of tumor suppressor genes (TSGs). Previous studies showed that DNMT1 and DNMT3B play an important role in CpG island methylation in tumorigenesis. Little is known about the role of DNMT3A in this process, especially in hepatocellular carcinoma (HCC). In the present study, increased DNMT3A expression in 3 out of 6 HCC cell lines and 16/25 (64%) HCC tissues implied that DNMT3A is involved in hepatocellular carcinogenesis. Depletion of DNMT3A in HCC cell line SMMC-7721 inhibited cell proliferation and decreased the colony formation (about 65%). Microarray data revealed that 153 genes were upregulated in DNMT3A knockdown cells and that almost 71% (109/153) of them contain CpG islands in their 5′ region. 13 of them including PTEN, a crucial tumor suppressor gene in HCC, are genes involved in cell cycle and cell proliferation. Demethylation of PTEN promoter was observed in DNMT3A-depleted cells implying that DNMT3A silenced PTEN via DNA methylation. These results provide insights into the mechanisms of DNMT3A to regulate TSGs by an epigenetic approach in HCC

Combination of Human Leukocyte Antigen and Killer Cell Immunoglobulin-Like Receptor Genetic Background Influences the Onset Age of Hepatocellular Carcinoma in Male Patients with Hepatitis B Virus Infection

To investigate whether killer cell immunoglobulin-like receptor (KIR) and human leukocyte antigen (HLA) genetic background could influence the onset age of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) infection, one hundred and seventy-one males with HBV-related HCC were enrolled. The presence of 12 loci of KIR was detected individually. HLA-A, -B, and -C loci were genotyped with high resolution by a routine sequence-based typing method. The effect of each KIR locus, HLA ligand, and HLA-KIR combination was examined individually by Kaplan-Meier (KM) analysis. Multivariate Cox hazard regression model was also applied. We identified C1C1-KIR2DS2/2DL2 as an independent risk factor for earlier onset age of HCC (median onset age was 44 for C1C1-KIR2DS2/2DL2 positive patients compared to 50 for negative patients, P=0.04 for KM analysis; HR = 1.70, P=0.004 for multivariate Cox model). We conclude that KIR and HLA genetic background can influence the onset age of HCC in male patients with HBV infection. This study may be useful to improve the current HCC surveillance program in HBV-infected patients. Our findings also suggest an important role of natural killer cells (or other KIR-expressing cells) in the progress of HBV-related HCC development

KIR and HLA Loci Are Associated with Hepatocellular Carcinoma Development in Patients with Hepatitis B Virus Infection: A Case-Control Study

BACKGROUND: Natural killer (NK) cells activation has been reported to contribute to inflammation and liver injury during hepatitis B virus (HBV) infection both in transgenic mice and in patients. However, the role of NK cells in the process of HBV-associated hepatocellular carcinoma (HCC) development has not been addressed. Killer cell immunoglobulin-like receptors (KIRs) are involved in regulating NK cell activation through recognition of specific human leukocyte antigen (HLA) class I allotypes. METHODOLOGY/PRINCIPAL FINDINGS: To investigate whether KIR and HLA genes could influence the risk of HBV-associated HCC development, 144 HBV-infected patients with HCC and 189 well-matched HBV infectors with chronic hepatitis or cirrhosis as non-HCC controls were enrolled in this study. The presence of 12 loci of KIR was detected individually. HLA-A, -B, -C loci were genotyped with high-resolution. HLA-C group 1 homozygote (OR = 2.02; p = 0.005), HLA-Bw4-80I (OR = 2.67; p = 2.0E-04) and combination of full-length form and 22 bp-deleted form of KIR2DS4 (KIR2DS4/1D) (OR = 1.89; p = 0.017) were found associated with HCC incidence. When the combined effects of these three genetic factors were evaluated, more risk factors were observed correlating with higher odds ratios for HCC incidence (P trend = 7.4E-05). Because all the risk factors we found have been reported to result in high NK cell functional potential by previous studies, our observations suggest that NK cell activation may contribute to HBV-associated HCC development. CONCLUSIONS/SIGNIFICANCE: In conclusion, this study has identified significant associations that suggest an important role for NK cells in HCC incidence in HBV-infected patients. Our study is useful for HCC surveillance and has implications for novel personalized therapy strategy development aiming at HCC prevention in HBV-infected patients

Parental expectation, cognitive development, and family function: a moderating inverted-U model

This paper analyses the influences of&nbsp;parental&nbsp;expectation on middle school students&#39;&nbsp;cognitive&nbsp;development, a subject that is seldom touched in Educational Data Mining (EDM) studies. Despite its anonymity in EDM literature,&nbsp;parental&nbsp;expectation plays a significant role in education. Even though&nbsp;parental&nbsp;expectation is widely studied in the domains of education and psychology, present&nbsp;models&nbsp;are too simple to specify its working path. As the influence of&nbsp;parental&nbsp;expectations is difficult to quantify, we conducted our investigation in one middle school in the city of Hangzhou by applying a set of questionnaires and&nbsp;cognitive&nbsp;assessments. Through the investigation, we verify an inverted-U-shaped relationship between&nbsp;parental&nbsp;expectation and&nbsp;cognitive&nbsp;performance under the&nbsp;moderation&nbsp;of&nbsp;family&nbsp;function. This result extends the EDM study by analyzing the&nbsp;family&#39;s contribution and provides a superior&nbsp;model&nbsp;of the impact of&nbsp;parental&nbsp;expectation.</p

Study on Electromagnetic Radiation Characteristics Based on HTS Maglev Levitation Test Line

As a new type of magnetic levitation train with the characteristics of self-stabilization and self-suspension, high-temperature superconducting magnetic levitation has developed to the test line research stage. In order to promote the rapid development of high-temperature superconducting magnetic levitation train engineering, and the main electromagnetic radiation sources are clarified by analyzing their working principles and structures. Then Ansoft Maxwell EM was used to build a 3D magnetic levitation train electromagnetic environment simulation model to simulate and predict the electromagnetic radiation characteristics of the magnetic levitation train system. Finally, a field EMF test was carried out to verify and assess the impact on the EM environment in the system. The results show that the permanent magnet track on the ground and the synchronous linear motor are the primary electromagnetic radiation sources, and the generated fields are mainly low-frequency fields and static magnetic fields. The low-frequency magnetic field inside the train decreases with the increase of frequency and is partially shielded by the carriage; The static magnetic field cannot be weakened by the carriage, and the static magnetic field inside the car decreases with the increase of height. All types of electromagnetic fields are far below the requirements of the relevant electromagnetic environmental standard limits, and have no effect on the electromagnetic radiation safety of the personnel inside the train and the surrounding environment; In considering of the special people who have pacemakers, static magnetic field suppression measures are studied, and the results show that the trains with high magnetic permeability permalloy as the shielding layer at the bottom of the vehicle greatly lower the static magnetic field within the train

Superiority of indocyanine green-enhanced near-infrared fluorescence-guided imaging for laparoscopic lymph node dissection in patients with early-stage endometrial cancer: A retrospective cohort study

Objective: Laparoscopic pelvic lymph node dissection (LPND), which is an effective therapy for endometrial cancer, is challenging because of the complexity of the procedure and the occurrence of postoperative complications. This study aimed to explore whether indocyanine green (ICG)-enhanced near-infrared (NIR) fluorescence-guided LPND is superior to LPND in the context of early-stage endometrial carcinoma. Methods: In this retrospective study, we included the medical records of 190 patients with early-stage endometrioid adenocarcinoma who underwent LPND at the Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine between January 2019 and January 2021. Depending on whether ICG-enhanced NIR fluorescence guidance was used, the patients were assigned to the ICG group or non-ICG group. Patients were followed-up for one year after surgery. Data on demographic characteristics, pathological results, operative outcomes, and complications were collected and analyzed. Results: The baseline characteristics were comparable between the ICG group and non-ICG group, including age, BMI, pregnancy history, and preoperative hemoglobin. For surgical outcomes, the patients in ICG group had significantly lower intraoperative blood loss (50 mL vs. 120 mL, p < 0.001), less postoperative pelvic drainage time (4.14 ± 1.44 d vs. 5.70 ± 1.89 d, p = 0.001), shorter duration of hospital stay (5.26 ± 1.41 d vs. 7.37 ± 1.85 d, p = 0.003), higher number of positive pelvic lymph nodes (PLNs) (1 vs. 0, p = 0.003), and more PLN-positive cases (16.0% vs. 3.6%, p = 0.003) than the patients in non-ICG group. However, no significant differences were noted in blood transfusion requirement, operative time, hemoglobin level decreases, number of PLNs harvested, or the presence of lymphocysts between the two groups. Conclusion: Our study showed that ICG-enhanced NIR fluorescence-guided operation may improve the accuracy and safety of LPND

B7 Family Members in Pancreatic Ductal Adenocarcinoma: Attractive Targets for Cancer Immunotherapy

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, with a five-year survival rate of approximately 5–10%. The immune checkpoint blockade represented by PD-1/PD-L1 inhibitors has been effective in a variety of solid tumors but has had little clinical response in pancreatic cancer patients. The unique suppressive immune microenvironment is the primary reason for this outcome, and it is essential to identify key targets to remodel the immune microenvironment. Some B7 family immune checkpoints, particularly PD-L1, PD-L2, B7-H3, B7-H4, VISTA and HHLA2, have been identified as playing a significant role in the control of tumor immune responses. This paper provides a comprehensive overview of the recent research progress of some members of the B7 family in pancreatic cancer, which revealed that they can be involved in tumor progression through immune-dependent and non-immune-dependent pathways, highlighting the mechanisms of their involvement in tumor immune escape and assessing the prospects of their clinical application. Targeting B7 family immune checkpoints is expected to result in novel immunotherapeutic treatments for patients with pancreatic cancer