Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

This study aims to explore the molecular mechanism of Ganoderma against gastric cancer based on network pharmacology, molecular docking, and cell experiment. The active components and targets of Ganoderma were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and gastric cancer-related targets from GeneCards and Online Mendelian Inheritance in Man(OMIM). The protein-protein interaction(PPI) network of the common targets was constructed with STRING, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the common genes based on Bioconductor and R language. The medicinal-disease-component-target network and medicinal-disease-component-target-pathway network were established by Cytoscape. Molecular docking was performed between β-sitosterol(the key component in Ganoderma) and the top 15 targets in the PPI network. Cell experiment was performed to verify the findings. A total of 14 active components and 28 targets of Ganoderma were retrieved, and the medicinal and the disease shared 25 targets, including caspase-3(CASP3), caspase-8(CASP8), caspase-9(CASP9), and B-cell lymphoma-2(BCL2). The common targets involved 72 signaling pathways and apoptosis and p53 signaling pathway may play a crucial role in the effect of Ganoderma against gastric cancer. β-sitosterol had strong binding activity to the top 15 targets in the PPI network. The in vitro cell experiment demonstrated that β-sitosterol inhibited gastric cancer AGS cell proliferation by inducing cell apoptosis and cell cycle arrest in the S phase, which might be related to the regulation of the p53 pathway. This study shows the multi-component, multi-target, and multi-pathway characteristics of Ganoderma against gastric cancer, which lays a scientific basis for further research on the molecular mechanism.
Ganoderma ; Humans ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Network Pharmacology ; Stomach Neoplasms/genetics*

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER NCT02063100 on ClinicalTrials.gov.

AIM:To investigate the regulatory effect of NADPH oxidase-4 (NOX-4) on PI3K signaling path-way in transforming growth factor-β1 (TGF-β1)-induced collagen type Ⅰ (collagen Ⅰ) synthesis from lung cancer cells and the mechanisms. METHODS:Human lung cancer A549 cells were cultured in vitro and stimulated with TGF-β1. The ex-pression of NOX family and collagen family at mRNA and protein levels as well as the PI3K class Ⅰ catalytic subunits and the activation of PI3K signaling pathway was measured. A549 cells were pre-treated with NOX-4 inhibitor diphenyleneiodo-nium (DPI), and the expression of collagen Ⅰ at mRNA level as well as the PI3K class Ⅰ catalytic subunits and the activa-tion of PI3K signaling pathway was measured upon TGF-β1 stimulation. RESULTS:TGF-β1 stimulated the expression of NOX-4 and collagen Ⅰ at mRNA and protein levels as well as the expression of PIK3CD and the activation of PI3K signaling pathway at a dose- and time-dependent manner. NOX-4 inhibitor DPI partly reversed TGF-β1-induced collagen Ⅰ expres-sion. Inhibition of NOX-4 down-regulated the degree of TGF-β1-stimulated activation of PI3K signaling pathway without effect on the expression of PIK3CD. CONCLUSION:NOX-4 participates in TGF-β1-induced collagen Ⅰ synthesis from lung cancer cells via regulating the activation of PI3K signaling pathway. TGF-β1/NOX-4/PI3K signaling pathway axis acts as a regulatory role in collagen Ⅰ synthesis from lung cancer cells.

BACKGROUNDPatients on hemodialysis have a high-mortality risk. This study analyzed factors associated with death in patients on maintenance hemodialysis (MHD). While some studies used baseline data of MHD patients, this study used the most recent data obtained from patients just prior to either a primary endpoint or the end of the study period to find the characteristics of patients preceding death.

METHODSParticipants were selected from 16 blood purification centers in China from January 2012 to December 2014. Patients' data were collected retrospectively. Based on survival status, the participants were divided into two groups: survival group and the death group. Logistic regression analysis was performed to determine factors associated with all-cause mortality.

RESULTSIn total, 4104 patients (57.58% male, median age 59 years) were included. Compared with the survival group, the death group had more men and more patients with diabetic nephropathy (DN) and hypertensive nephropathy. The patients preceding death also had lower levels of diastolic blood pressure, hemoglobin, serum albumin, serum calcium, serum phosphate, Kt/V, and higher age. Multivariate analysis revealed that male sex (odd ratio [OR]: 1.437, 95% confidence interval [CI]: 1.094-1.886), age (OR: 1.046, 95% CI: 1.036-1.057), and presence of DN (OR: 1.837, 95% CI: 1.322-2.552) were the risk factors associated with mortality. High serum calcium (OR: 0.585, 95% CI: 0.346-0.989), hemoglobin (OR: 0.974, 95% CI: 0.967-0.981), albumin (OR: 0.939, 95% CI: 0.915-0.963) levels, and dialysis with noncuffed catheter (OR: 0.165, 95% CI: 0.070-0.386) were protective factors based on a multivariate analysis.

CONCLUSIONSHemodialysis patients preceding death had lower hemoglobin, albumin, and serum calcium levels. Multivariate analysis showed that male sex, age, DN, low hemoglobin, low albumin, and low serum calcium were associated with death in hemodialysis patients.

Adult ; Aged ; China ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Renal Dialysis ; adverse effects ; mortality ; Retrospective Studies ; Risk Factors

Objective:To explore effects of trehalose as a cryopreserve agent on survival rate of fatty tissue after cryopreservation.Methods:The liposuction was used on the abdomen of adult female.After centrifugation and purification,adipose was randomized into the following three groups,the trehalose group,the fetal bovine serum (FBS)+ 10％DMSO group and the physiological saline group.The specimens were cryopreserved at-196 ℃ for 3 months and then the HE staining,glucose transfer method and CK method were used to detect the cell survival rate in each group.Results:The activity of adipose in the trehalose group and FBS+10％DMSO group adipose was higher than that in the physiological saline group (P＜0.05);while there was no significant difference between the trehalose group and FBS+10％DMSO group (P＞0.05).Conclusion:As cryoprotectant,trehalose could keep fat cell viability,and adipose tissue can be used for clinical transplantation after 3 months' freezing.

This study is purposed to investigate the effects of praeruptorin A (PA) and praeruptorin C (PC) on UGT1A1 in HepG2 cells through hCAR pathway. PA and PC were incubated with HepG2 cells for 24 h and 48 h, mRNA and protein expressions of UGT1A1 were determined by real-time PCR and Western blotting assays. Additionally, effects of PA and PC on UGT1A1 mRNA and protein expressions were also measured after transient transfection of a specific CAR siRNA for 72 h in HepG2 cells. UGT1A1 mRNA and protein expression levels were significantly increased by PA and PC after incubation for 48 h. Moreover, the mRNA and protein up-regulations of UGT1A1 were attenuated by transient transfection of a specific CAR siRNA, suggesting the induction was mediated by CAR. The results suggest that PA and PC can significantly up-regulate UGT1A1 expression partially via the CAR-mediated pathway.
Apiaceae ; chemistry ; Coumarins ; isolation & purification ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Glucuronosyltransferase ; genetics ; metabolism ; Hep G2 Cells ; Humans ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; genetics ; metabolism ; Receptors, Cytoplasmic and Nuclear ; genetics ; metabolism ; Signal Transduction ; Transfection

Adolescent ; Adult ; Aged ; Aged, 80 and over ; China ; Disasters ; Earthquakes ; Female ; Health Status ; Humans ; Male ; Middle Aged ; Psychology, Social ; Young Adult

BACKGROUND AND OBJECTIVEThe primary submucous type of nasopharyngeal carcinoma (NPC) or the recurrent NPC in the parapharyngeal space is difficult to be diagnosed histologically by conventional biopsy because of the obstruction of the surrounding structures. This study was performed to evaluate the needle biopsy approach through the madibular area into the parapharyngeal space under the guidance of computed tomography (CT) for NPC.

METHODSBetween July 6, 2005 and October 23, 2009, a total of 6 patients were enrolled into the study. Two patients with cervical lymph node metastasis were clinically suspicious of NPC according to their clinical manifestations. However, no cancer cell could be found by repeated nasopharyngeal biopsies followed by histologic examinations. The other 4 patients were diagnosed with recurrent NPCs by magnetic resonance imaging (MRI) or/and positron emission tomography (PET)-CT scan, showing tumors in the parapharyngeal spaces in 3 patients and enlarged retropharyngeal lymph node in 1 patient. The CT-guided puncture was performed through the mandibular skin and the cutting needle biopsy was taken at the parapharyngeal space focus.

RESULTSAll the cutting needle biopsies of projected locations have been performed safely. Finally, all the 7 specimens met the requirement of pathologic diagnosis and the cases were all confirmed histologically to be NPCs. The main complication was mild ache at the puncture point. No blood vessel or nerve was injured and no patient needed special treatment.

CONCLUSIONSThe CT-guided puncture biopsy of the parapharyngeal space through the mandibular area is simple and feasible. It can be an additional option for routine nasopharyngeal biopsy.

Adult ; Aged ; Biopsy, Needle ; methods ; Female ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Magnetic Resonance Imaging ; Male ; Mandible ; Middle Aged ; Nasopharyngeal Neoplasms ; diagnosis ; diagnostic imaging ; pathology ; Neoplasm Recurrence, Local ; Pharynx ; pathology ; Positron-Emission Tomography ; Tomography, X-Ray Computed

BACKGROUND: The soft tissues would shrink with nasal framework collapse following surgical trauma, which cause aseptic inflammation, lead to parts of cartilage resorption. Accordingly, long-term saddle nose deformity usually accompanied by short nasal columella. Complications such as skin perforation or ulceration would appear if corrected the deformity using medical silicone rubber with large tension.OBJECTIVE: To explore the effectiveness of repairing post-traumatic saddle nose deformity with autologous costal cartilage transplantation.METHODS: A total of 21 cases with post-traumatic saddle nose deformity accompanied by short nasal columella were selected, including 6 males and 15 females, aged 16 45 years. All of the cases had trauma history and agreed with the treatment. The costal cartilage was obtained from the seventh rib and formed to babylon weeping willow leaf shape and columella nasi stent to repair post-traumatic saddle nose deformity. The "V-Y" progradation suture was used in the philtrum introcession and the botton of nasal columella to extend the nasal columella. The recovery of saddle nose deformity after transplantation, discharge of transplanted cartilage, as well as the incision scar status was observed.RESULTS AND CONCLUSION: The results were satisfactory and there were no complications after transplantation. All the cases were followed up from 6 months to 2 years. No case suffered costal cartilage grafts discharge or chondral deformation. The scar was little at the bottom of nasal columella. It is an ideal method for repairing post-traumatic saddle nose deformity using transplantation of autologous costal cartilage with "V-Y" progradation suture.