miR-491-5p regulates the susceptibility of glioblastoma to ferroptosis through TP53.

BACKGROUND: Ferroptosis has excellent potential in glioblastoma (GBM) therapy. In this study, we attempted to explore the effect of miR 491-5p on ferroptosis in GBM. METHODS: In this study, publicly available ferroptosis-related genome maps were used to screen genes upregulated in GBM and their target genes. The Spearman correlation coefficient was applied to analyze the correlation between the tumor protein p53 gene (TP53) and miR-491-5p. The expressions of miR-491-5p and TP53 were determined. The protein abundances of the TP53-encoded factors p53 and p21 were measured. Cell proliferation, migration and invasion were assessed. We pretreated U251MG cells and GBM mice with a ferroptosis inducer (erastin). The mitochondrial state was observed. The contents of reactive oxygen species (ROS), total Fe and Fe2+ were calculated. RESULTS: The level of TP53 was significantly increased in GBM and negatively correlated with miR-491-5p. miR-491-5p overexpression promoted U251MG cell proliferation, migration and invasion and interfered with the p53/p21 pathway. TP53 supplement reversed the effects of miR-491-5p. U251MG cells and GBM mice exhibited significant accumulations of ROS and iron. Erastin promoted the expression of TP53. Inhibition of TP53 reversed erastin-induced physiological phenotypes. Moreover, miR-491-5p overexpression caused a decrease in the number of damaged mitochondria and the contents of ROS, total Fe and Fe2+. TP53 supplement disrupted miR-491-5p-repressed ferroptosis. Erastin could inhibit GBM growth, and miR-491-5p overexpression impeded the therapeutic effect of erastin. CONCLUSIONS: Our findings reveal the functional diversity of miR-491-5p in GBM and suggest that miR-491-5p/TP53 signaling hinders the sensitivity of GBM to ferroptosis through the p53/p21 pathway.

Relationship between tumor viability during treatment and the clinical outcomes of patients with bladder/prostate rhabdomyosarcoma: a single-center experience.

BACKGROUND: To analyze the relationship between tumor viability in specimens retrieved at second-look procedures (SLPs) and clinical outcomes in patients with bladder/prostate rhabdomyosarcoma (BP RMS). METHODS: We retrospectively analyzed patients` characteristics, times between diagnoses and SLPs, types of SLPs, the pathological findings, and clinical outcomes between January 2003 and May 2014. RESULTS: A total of 29 patients underwent at least one SLP before completing chemotherapy, including 24 boys and 5 girls. The mean age was 36 months. No patients with clinical/radiographic complete responses (CRs) had viable tumor cells and 7/18 patients (38.9%) without CR had no viable tumor cells. Seven patients experienced tumor relapse, progression, and metastasis, and three of these survived. Five-year event-free survival (EFS) rates were 88.5% in 18 patients without viable tumor at SLPs and 54.5% in 11 patients with viable tumor (Cox proportional hazards adjusted P=0.045). The respective five-year overall survival (OS) rates were 94.1% and 72.7% (Cox proportional hazards adjusted P=0.175). CONCLUSIONS: EFS was increased in patients with BP RMS having no viable tumor cells; however, OS was comparable in patients with and without viable tumor cells. Patients who achieved CR during the treatment generally had no viable tumor cells.

Inflammatory Myofibroblastic Tumor After Treatment of Wilms Tumor in a 6-Year-Old Boy: A Case Report and Literature Review.

Inflammatory myofibroblastic tumor (IMT) is a rare tumor with an indolent course. It is less often reported as a second tumor that occurs after treatment of malignant tumors in pediatric patients. Here, we report a case of IMT following Wilms tumor (WT), and conduct a literature review concerning IMTs and WT to evaluate the diagnostic possibility of IMT as a second tumor. The coexistence of the 2 tumors may cause confusion as to whether they share genetic links or that IMTs may appear as late effects of the treatment of WT.

A disposable paper-based hydrophobic substrate for highly sensitive surface-enhanced Raman scattering detection.

Detection of target analytes with high sensitivity and reproducibility remains a challenge for surface-enhanced Raman scattering (SERS) due to the lack of cost-effective and highly sensitive substrates. In this study, a hydrophobic SERS substrate capable of concentrating nanoparticles and analytes was prepared by spin-coating lubricating liquid onto commercial paper. The condensation effect of the paper-based hydrophobic substrate induced aggregation of gold nanoparticles (Au NPs) to generate ''hot spots'' for SERS and to drive analytes to the hot-spot areas for more sensitive detection. The obtained SERS signal intensity was 5-fold higher than that obtained using common paper, and a detection limit (LOD) of 4.3 × 10-10 M for rhodamine 6G (R6G) was achieved. Randomly selected points on the substrate and different batches of substrates all exhibited high reproducibility, and the relative standard deviation (RSD) at 1362 cm-1 is approximately 11%. A further application of the hydrophobic substrate was demonstrated by the detection of cytochrome C within a linear detection range of 3.90 × 10-8 M-1.25 × 10-6 M. In addition, the prepared substrate can obtain identifiable SERS spectra of cancer cells and non-cancer cells because a large number of AuNP or Au NPs clusters can adhere to cells, resulting in the construction of a 3D hotspot matrix. The disposable hydrophobic paper substrate eliminates the problem of solution diffusion, and also provides an effective platform for biomolecular screening detection.

Inflammatory Myofibroblastic Tumor of the Urinary Bladder and Ureter in Children: Experience of a Tertiary Referral Center.

PURPOSE: To present the clinicopathological characteristics and outcome of children with bladder and ureteral inflammatory myofibroblastic tumors (IMTs) in our center. METHODS: We reviewed the medical records of patients with bladder and ureteral IMTs from 2010 to 2018. We recorded patients' demographic data, presentation, hemoglobin level, presence of hydronephrosis, tumor size, treatment, and outcomes. RESULTS: Eight patients with bladder IMTs and 3 with ureteral IMTs were treated at our center during this period. The mean age was 7.1 years. Four patients presented with anemia at diagnosis with the mean hemoglobin level 84.5 g/L. Among patients with bladder IMTs, 5 were male and 3 were female. The most common symptom was lower urinary symptoms in 6 patients, followed by hematuria in 4 patients. 2 patients had complications of hydronephrosis and hydroureter. Among patients with ureteral IMTs, 2 were male and one was female. The most common symptom was abdominal pain, and 3 patients presented with upper urinary tract dilation. All patients underwent surgery. A total of 81.8% were positive for anaplastic lymphoma kinase. Cytokeratin (CK) expression was present in all patients with bladder IMTs, while it was negative in 2 patients with ureteral IMTs. During mean follow-up of 43.4 months, all patients survived event-free. CONCLUSION: The presence of hydronephrosis and hydroureter is rare in patients with bladder IMTs. Anemia caused by hematuria should be raised the index of suspicion for IMTs. Children with bladder and ureteral IMTs had excellent prognosis. The expression pattern of CK varied between bladder and ureteral IMTs.

Curcumin ameliorates cisplatin-induced cystopathy via activating NRF2 pathway.

OBJECTIVES: The present work evaluated preventive effect of curcumin on cisplatin-induced bladder cystopathy. METHODS: Fifteen female rats were divided into (i) Control group administered with physiological saline solution for 5 days; (ii) Cis-P group injected with cisplatin (6 mg/kg); and (iii) Cis-Cur group given cisplatin (6 mg/kg) with curcumin for 5 consecutive days. The function of bladder was measured by means of urodynamic analysis. Furthermore, hematoxylin-eosin staining and Masson trichrome staining were performed for morphological analysis. The cell apoptosis was evaluated through terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay and flow cytometry. The expression of nerve growth factor (NGF), NF-E2-related factor 2, and hemeoxygenase-1 (HO-1) levels were measured through Western blotting. RESULTS: Urodynamic assay and histopathological manifestations revealed that curcumin ameliorated the bladder dysfunction induced by cisplatin. The level of cisplatin-induced apoptosis in the bladder decreased following curcumin treatment. Also, the increased protein expression of NGF indicated that the curcumin could offer neuroprotection for bladder against cisplatin. Curcumin also activated NRF2, and elevated the expression of HO-1, but curcumin could not rescue cisplatin-induced apoptosis in the cell lines with knockdown of NRF2. CONCLUSIONS: Taken together, the results of this paper showed that curcumin could ameliorate cisplatin-induced cystopathy and inhibit the apoptosis of bladder cell in cisplatin-treated rats. This may be attributed to curcumin's broad biological functions, particularly antioxidant effect, and to its ability to activate the NRF2 protein.

Differential expression of cytokeratin 14 and 18 in bladder cancer tumorigenesis.

It has been previously suggested that cytokeratins (CKs) are important diagnostic and prognostic biomarkers for urothelial lesions. Hence it is imperative to understand the expression pattern of cytokeratins during formation of papillary bladder cancer, which was the objective of the current study. Expression pattern of CK14 and CK18 were examined using immunohistochemical staining in a mice model of papillary bladder cancer. Twenty female mice were divided into two groups-group 1 (NT) and group 2, which received N-butyl- N-(4-hydroxybutyl) nitrosamine (BBN) for 20 weeks plus one week without treatment. Following histological classification of bladder lesions, CK14 and CK18 immunostaining was assessed according to its distribution and intensity. In NT animals, both basal cells and umbrella cells showed sporadic positive staining for CK14 and CK18, respectively. In BBN group, hyperplastic lesions showed significantly more CK14 and significantly less CK18 staining ( P < 0.05 in each case). Invasive carcinomas showed increased CK14 immunostaining in all epithelial layers. Cumulatively, our data indicate that altered CK14 (high) and CK18 (low) expression is perhaps an early event in bladder cancer tumorigenesis in females at least and is characteristic of both urothelial superficial pre-neoplastic and neoplastic lesions. Impact statement Studies have shown that expression of cytokeratins (CKs) or their altered distribution affects the bladder cancer pathogenesis and disease outcome, while the underlying mechanisms are not clear. The present study aims to explore the expression pattern of CK14 and CK18 during formation of papillary bladder cancer. The results showed that hyperplastic lesions showed significantly more CK14 and significantly less CK18 staining and invasive carcinomas showed increased CK14 immunostaining in all epithelial layers in N-butyl- N-(4-hydroxybutyl)nitrosamine (BBN)-induced mouse model. The results indicate that altered CK14 (high) and CK18 (low) expression is perhaps an early event in bladder cancer tumorigenesis and is characteristic of both urothelial superficial pre-neoplastic and neoplastic lesions, which may provide the early diagnosis index.

[Experimental study on osteogenesis of acellular porcine pericardium in guided bone regeneration].

PURPOSE: To observe the retention time and effect of acellular porcine pericardium (APP) in bone regeneration for rabbit femoral bone defects. METHODS: APP was prepared as follows: fresh porcine pericardium was chosen, high and low osmotic NaCl solution were used to soak the specimen alternately, trypsin+EDTA were used for digest, and then immersed with TritonX-100, cross-linked by using glutaraldehyde. 24 New Zealand rabbits were selected, and the area of bone defect was created 8 mm×8 mm×5 mm in size on bilateral distal femur. Stochastic method was used for grouping. One side of bone defect was covered with APP (experimental group); and the other side was covered without APP (control group). General observation, X-ray examination, histological examination, and bone mineral density (BMD) were performed 4 weeks, 8 weeks and 12 weeks after operation. SPSS18.0 software package was used for statistical analysis. RESULTS: After surgery, all wounds healed without complications. Under general observation, there were some fibrous cysts covered on the surface of APP. BMD (P<0.05) in the experimental group was significantly greater than that in the control group. On histological examination, the rate of osteogenesis in the experimental group was faster than that in the control group. CONCLUSIONS: Bone regeneration can be achieved using APP in the repair of rabbit bone defects. The retention time of APP can meet the needs of osteogenesis.

Effectiveness and safety of selected bone marrow stem cells on left ventricular function in patients with acute myocardial infarction: a meta-analysis of randomized controlled trials.

BACKGROUND: Concerns regarding the use of selected bone marrow stem cells (BMSCs) in the field of cardiac repair after acute ischemic events have been raised. The current meta-analysis aimed to assess the efficacy and safety of selected BMSC transplantation in patients with acute myocardial infarction (AMI) based on published randomized controlled trials (RCTs). METHODS: A systematic literature search of PubMed, Ovid LWW, BIOSIS Previews, and the Cochrane library from 1990 to 2014 was conducted. Results from RCTs involving subjects with AMI receiving selected BMSC therapy and followed up for at least 6 months were pooled. RESULTS: Eight trials with a total of 262 participants were included. Data were analyzed using a random effects model. Overall, selected BMSC therapy improved left ventricular ejection fraction (LVEF) by 3.17% (95% confidence interval [CI] 0.57-5.76, P=0.02), compared with the controls. There were trends toward reduced left ventricular end-systolic volume (LVESV) and fewer major adverse cardiac events (MACEs). Subgroup analysis revealed a significant difference in LVEF in favor of selected BMSC therapy with bone marrow mesenchymal stem cells (BMMSCs) as the cell type. CONCLUSIONS: Transplantation of selected BMSCs for patients with AMI is safe and induces a significant increase in LVEF with a limited impact on left ventricular remodeling.

[Analysis of virulence-related properties of P. gingivalis clinical isolates].

PURPOSE: To analyze the relation of virulence properties and pathogenicity of Porphyromonas gingivalis (P.gingivals) isolated from Chinese patients. METHODS: Based on the previous analysis of virulence properties, investigations of pathogenicity properties, including the adhesion to host cells, gingipain activities, and resistance to host immune reaction were performed to analyze the diversity of pathogenic properties of these strains. SAS 8.02 software package was used for statistical analyses. RESULTS: Less-virulent type strain showed higher adherence ability to host red blood cells and weaker resistance to serum killing, while virulent type strain showed the opposite reactions. However, the clinic isolates presented just the opposite relationship between virulence properties and pathogenicity. In addition, there was no obvious correlation between gingipain activities and virulence properties of P. gingivalis strains. CONCLUSIONS: The results suggested that there is no obvious linkage between the P. gingivalis virulence properties and pathogenicity diversity.

Treatment of malignant triton tumor in zygomatic region.

Malignant triton tumor (MTT) is extremely rare and supposed to be highly aggressive because of high propensity for local recurrence and metastasis. To date, only about 170 cases were reported in various body locations including trunks, maxillary sinus, neck, extremities, retroperitoneal, and so on. We present a case of MTT in the zygoma with good outcome. A 27-year-old male patient with progressive swelling and pain in the right zygoma was proved to have an MTT by biopsy. Radical resection accompanying postoperative radiotherapy was adopted, and then the soft and hard tissue defects were repaired by prosthesis. The patient recovered well and was satisfied with the facial contour. At 45-month follow-up, there was no recurrence or metastasis that occurred. According to literature review, one third of MTTs appeared in the head and neck regions and seem to have a better prognosis. Radical resection is the most important remedy, and adjuvant radiotherapy could be helpful. With early finding and effective treatments, satisfactory outcome could be achieved.

Surgical treatment of a giant neurofibroma.

Neurofibromatosis type 1, an autosomal dominant inherited disease, presents pathologic symptoms of multiple systems, including neurofibromatosis, skeletal dysplasia, café-au-lait spots in skins, and so on. A 45-year-old man with neurofibromatosis type 1 was reported in this article. The patient presented a giant neurofibroma in his head and neck, dysplasia of skull, facial bones and spinal columns, and multiple café-au-lait spots in systematic skins. Satisfactory curative effects were obtained in this case after tumor resection and prosthesis implantation.

Surgical resection of a huge cemento-ossifying fibroma in skull base by intraoral approach.

Cemento-ossifying fibroma, also known as ossifying fibroma, usually occurs in the mandible and less commonly in the maxilla. The huge example in the skull base is even rare. We present a case of a huge cemento-ossifying fibroma arising below the skull base of a 30-year-old woman patient. Radiologic investigations showed a giant, lobulated, heterogeneous calcified hard tissue mass, which is well circumscribed and is a mixture of radiolucent and radiopaque, situated at the rear of the right maxilla to the middle skull base. The tumor expands into the right maxillary sinus and the orbital cavity, fusing with the right maxilla at the maxillary tuberosity and blocking the bilateral choanas, which caused marked proptosis and blurred vision. The tumor was resected successfully by intraoral approach, and pathologic examination confirmed the lesion to be a cemento-ossifying fibroma. This case demonstrates that cemento-ossifying fibroma in the maxilla, not like in the mandible, may appear more aggressive because the extensive growth is unimpeded by anatomic obstacles and that the intraoral approach can be used to excise the tumor in the skull base.

Aniridia rings implantation for treatment of congenital aniridia combined with cataract surgery: a case report.

We describe the successful treatment in a patient with bilateral congenital aniridia and cataract by insertion of capsular tension rings and IOL.

[Correction of progressive hemifacial atrophy using dermis-fat graft and Medpor implant shaped by reverse engineering technique].

OBJECTIVE: To evaluate the therapeutic effect of dermis-fat graft combined with Medpor implant shaped by reverse engineering technique in the correction of the progressive hemifacial atrophy. METHODS: A skull model was made by rapid prototyping and the bony deficiency model was acquired with reverse engineering technique. The Medpor implant was shaped precisely based on the deficiency model and implanted with dermis-fat graft at the same stage. RESULTS: 11 cases were treated successfully without infection, necrosis and rejection. The patients were followed up for six months to one year with satisfactory cosmetic improvement. The dermis-fat graft survived without obvious absorption. CONCLUSION: The technique can correct both the bony and soft tissue deficiency for progressive hemifacial atrophy. It is very practical and easily performed with reliant results and less morbidity.