Effects of Purine Metabolism-Related LINC01671 on Tumor Heterogeneity in Kidney Renal Clear Cell Carcinoma.

BACKGROUND: Renal cell carcinoma has several subtypes, with kidney renal clear cell carcinoma (KIRC) being the most common and heterogeneous. Purine metabolism is associated with cancer progression. However, the role of purine metabolism-related long non-coding RNAs (lncRNAs) in KIRC remains unknown. METHODS: KIRC were grouped into Cluster-1 and Cluster-2 based on purine genes. Limma package was used to identify differentially expressed lncRNAs between two classes of purine genes. Single-factor screening was used followed by random forest dimensionality reduction and Lasso method to screen lncRNAs. A risk score model (Purine Score) containing the 3 lncRNAs was developed using the Lasso method. RESULTS: A total of 22 differentially expressed lncRNAs were identified. These were reduced to a final set of three (LINC01671, ARAP1-AS1 and LINC02747). Age and metastasis (M) were identified as independent prognostic factors for KIRC using univariate and multivariate Cox analysis. An abnormal immune cell response was also associated with patient survival. The Purine Score correlated with abnormal expression of immune checkpoint genes. Genetic analysis of KIRC found somatic mutations in TP53, TRIOBP, PBRM1, PKHD1, VHL, NPHP3, TLN2, CABIN1, ABCC6, XIRP2, and CHD4. In vitro cell experiments showed that knockdown of LINC01671 promoted the proliferation and migration of 786-O cells, while inhibiting apoptosis. Overexpression of LINC01671 inhibited the proliferation and migration of CAKI-1 cells, while promoting apoptosis. Gene Set Enrichment Analysis (GSEA) analysis revealed that LINC01671 was significantly enriched in the MAPK, NF-kappa B, mTOR, PI3K-Akt, and Wnt signaling pathways. CONCLUSIONS: LINC01671 may be a novel prognostic marker with important therapeutic value for KIRC.

Rosacea Aggravated after Intracutaneous Injection of Poly-L-lactic Acid through a Stamp-type Microneedle.

Injectable poly-L-lactic acid (PLLA) has been widely used for skin texture improvement, volume augmentations of the face or body, and other cosmetic or reconstructive treatment. Despite its significant efficacy, many side effects have also been reported. Here, we describe a case of rosacea aggravated by intracutaneous injection of PLLA using a mesogun injector with stamp-type microneedle. After the treatment, the patient exhibited aggravated rosacea symptoms, such as flushing and erythema. A possible mechanism for the exacerbations might be that PLLA stimulated subclinical inflammatory reaction in the skin. We suggest that PLLA injection should be administered more cautiously in patients with rosacea or other inflammatory skin lesions.

HOXA11-AS induces cisplatin resistance by modulating the microRNA-98/PBX3 axis in nasopharyngeal carcinoma.

Long non-coding RNA homeobox A11-antisense RNA (HOXA11-AS) has been implicated in cisplatin (DDP) resistance in multiple types of cancer. The purpose of the present study was to investigate the role of HOXA11-AS in DDP-resistant nasopharyngeal carcinoma (NPC) cells. The expression levels of HOXA11-AS were examined using reverse transcription-quantitative PCR. Cell viability was measured using a Cell Counting Kit-8 assay, and a TUNEL assay was utilized to assess cell apoptosis. The expression levels of apoptosis-related factors (Bax and Bcl-2) were detected by western blot analysis. The interaction between microRNA-98 (miR-98) and HOXA11-AS or pre-B-cell leukemia homeobox 3 (PBX3) was demonstrated using bioinformatics analysis, dual-luciferase reporter assays and RNA immunoprecipitation assays. HOXA11-AS and PBX3 expressions levels were upregulated, whereas miR-98 levels were downregulated in DDP-resistant NPC tissues. Patients with NPC with high HOXA11-AS expression had a low survival rate. Knockdown of HOXA11-AS enhanced the DDP sensitivity of DDP-resistant NPC (5-8F/DDP and SUNE1/DDP) cells, which was demonstrated by the accelerated apoptosis. In addition, HOXA11-AS inhibited the expression levels of miR-98 through direct interaction. Furthermore, miR-98 inhibition counteracted the inductive effect of HOXA11-AS-knockdown on the DDP sensitivity of NPC cells. PBX3 was a target of miR-98 and was positively modulated by HOXA11-AS. Overexpression of PBX3 reversed the suppressive effect of HOXA11-AS silencing on the DDP resistance of NPC cells. The data demonstrated that HOXA11-AS enhanced DDP resistance in NPC via the miR-98/PBX3 axis, providing a potential therapeutic target for patients with DDP-resistant NPC.

KIF9-AS1 promotes nasopharyngeal carcinoma progression by suppressing miR-16.

Long non-coding RNAs (lncRNAs) have been reported to serve a crucial role in the progression of nasopharyngeal carcinoma (NPC); however, the underlying molecular mechanisms of lncRNA KIF9-AS1 in the tumorigenesis of NPC remains poorly understood. Reverse transcription-quantitative PCR was used to analyze the expression levels of KIF9-AS1 and microRNA (miR)-16, and Cell Counting Kit-8, wound healing and Transwell assays were used to determine the cell viability, invasion and migration, respectively, of NPC cells. In addition, a dual-luciferase reporter assay was used to analyze the direct interaction between KIF9-AS1 and miR-16. NPC stage was classified according to the seventh edition of the AJCC staging system. The results revealed that KIF9-AS1 expression levels were upregulated in NPC tissues and cell lines. In addition, miR-16 was demonstrated to directly interact with KIF9-AS1 and inhibit KIF9-AS1 expression levels, whereas the miR-16 inhibitor rescued the effects of the KIF9-AS1-knockdown in NPC cells. Furthermore, the expression levels of KIF9-AS1 were upregulated, while those of miR-16 were downregulated in NPC tissues. Notably, the expression levels of KIF9-AS1 were observed to be significantly more upregulated in advanced tumors (III-IV vs. I-II) and patients with high KIF9-AS1 expression levels exhibited a worse prognosis. In conclusion, the findings of the present study suggested that KIF9-AS1 may promote the progression of NPC by targeting miR-16, thus KIF9-AS1 may be a novel molecular target for NPC therapy.

Long non-coding RNA HOXA-AS2 promotes the expression levels of hypoxia-inducible factor-1α and programmed death-ligand 1, and regulates nasopharyngeal carcinoma progression via miR-519.

Nasopharyngeal carcinoma (NPC) is a rare malignancy arising from the nasopharyngeal epithelium and belongs to the group of head and neck cancer types, which are usually associated with viral and/or environmental influences, as well as heredity causes. A recent study reported that the long non-coding RNA (lncRNA) HOXA cluster antisense RNA 2 (HOXA-AS2) may be a prognostic biomarker in NPC; however, the specific mechanisms underlying NCP progression are yet to be determined. The aim of the present study was to investigate the biological role of HOXA-AS2 in NPC. In the present study, the gene expression levels of HOXA-AS2, miR-519, hypoxia-inducible factor (HIF-1α) and programmed death-ligand 1 (PD-L1) were detected using reverse transcription-quantitative PCR (RT-qPCR) analysis and western blotting. Bioinformatics analysis and a dual luciferase reporter assay were performed to predict and confirm the direct interactions between HOXA-AS2 and microRNA (miR)-519, as well as between miR-519 and HIF-1α. A MTT assay was used to detect the cell viability, while cell migratory and invasive abilities were assessed using wound healing and Transwell assays. HOXA-AS2 and HIF-1α were found to be significantly upregulated in NPC tumor tissues, as well as in NPC cell lines. The overexpression of HOXA-AS2 significantly enhanced NPC progression, including the cell proliferative, migratory and invasive abilities. HOXA-AS2 was identified to directly bind to miR-519, whereas a miR-519 inhibitor significantly rescued the HOXA-AS2 knockdown-attenuated progression of NPC. Moreover, miR-519 could bind to HIF-1α and PD-L1. Overexpression of HIF-1α and PD-L1 significantly promoted NPC progression and partially recovered the phenotype of NPC cells attenuated by HOXA-AS2 knockdown. In conclusion, the present study demonstrated that HOXA-AS2/miR-519/HIF-1α and/or HOXA-AS2/miR-519/PD-L1 may be a novel mechanism regulating the progression of NPC, which may facilitate the development of targeted clinical therapy.

Long Non-Coding RNA DLEU1 Up-Regulates BIRC6 Expression by Competitively Sponging miR-381-3p to Promote Cisplatin Resistance in Nasopharyngeal Carcinoma.

BACKGROUND: Cisplatin (DDP) resistance has become an obstacle to chemotherapy for nasopharyngeal carcinoma (NPC) patients. Recent evidences indicate that long noncoding RNAs (lncRNAs) are involved in tumorigenesis and chemoresistance. However, the potential role of lncRNAs in NPC progression remains largely unknown. METHODS: First, lncRNA expression profiling in NPC was performed via microarray analysis. To explore the involvement of DLEU1 in DDP resistance, loss-of-function experiments were employed in vitro and in vivo. Bioinformatics analysis, luciferase reporter assay, qRT-PCR, and Western blot assays were used to investigate the underlying mechanisms. RESULTS: Here, we identified 153 differentially expressed lncRNAs. Among them, DLEU1 was remarkably up-regulated in NPC tissues and associated with worse outcome. Knock-down of DLEU1 could sensitize NPC cells to DDP in vitro and in vivo. Further investigations revealed that DLEU1 positively regulated BIRC6 expression via its competing endogenous RNA (ceRNA) activity on miR-381-3p. We also observed that BIRC6 overexpression or miR-381-3p silence could significantly reverse DLEU1-dependent DDP resistance. CONCLUSION: Our data suggest that DLEU1 acts as an oncogene to promote DDP resistance and BIRC6 expression in NPC through interacting with miR-381-3p, which may help to develop new strategy against NPC chemoresistance.

Solely lung-involved IgG4-related disease : a case report and review of the literature.

By analyzing the clinical data of 1 case of IgG4-related lung disease(IgG4-RLD) and the review of literature, the author investigated the clinical characteristics of IgG4-RLD. IgG4-RLD is a rare disease characterized by significant elevation of serum IgG4 and infiltration of a large number of IgG4+ plasma cells. The clinical manifestations of the disease were nonspecific, and the imaging features were mixed with several types. The disease can only be involved in the lung, but also multiple organ involvement. Solely lung-involved IgG4-RD is not only extremely rare but also easily misdiagnosed as tuberculosis, lung cancer, lymphoma and other common pulmonary diseases. Histopathological examination is the key to the diagnosis of the disease. Corticosteroids are the first choice of treatment, and the overall prognosis is good.

[Evaluation criteria for rat skin anaphylactoid test].

This study is to explore characteristic indexes in evaluation criteria for rat skin anaphylactoid test comparing skin blue spot OD values at the treated position and the control position in the same animal. Common contrast agents, traditional Chinese medicine injections and injections' active pharmaceutical ingredients or excipients in the existing clinical anaphylactoid reaction reports were taken as test drugs in the rat skin anaphylactoid test to define the K value: K > 2 represents positive anaphylactoid reaction, 1.2 ≤ K ≤ 2 represent doubtable anaphylactoid; K < 1.2 represents negative anaphylactoid reaction, which were taken as the criteria for evaluating anaphylactoid of tested drugs. The evaluation result and that for classic criteria were compared to study the applicability of K value. According to the comparison, K value, as the evaluation criteria in the rat skin anaphylactoid test, can more truly reflect the actual situation of skin aizen and minimize the error caused by animal individual factors. Compared with positive and negative two-level criteria for blue spot diameter, K value's positive, doubtable and negative three-level criteria are more objective and accurate. Therefore, K value can be used as the evaluation criteria in the rat skin anaphylactoid test.

Evaluation criteria for rat skin anaphylactoid test / 中国中药杂志

This study is to explore characteristic indexes in evaluation criteria for rat skin anaphylactoid test comparing skin blue spot OD values at the treated position and the control position in the same animal. Common contrast agents, traditional Chinese medicine injections and injections' active pharmaceutical ingredients or excipients in the existing clinical anaphylactoid reaction reports were taken as test drugs in the rat skin anaphylactoid test to define the K value: K > 2 represents positive anaphylactoid reaction, 1.2 ≤ K ≤ 2 represent doubtable anaphylactoid; K < 1.2 represents negative anaphylactoid reaction, which were taken as the criteria for evaluating anaphylactoid of tested drugs. The evaluation result and that for classic criteria were compared to study the applicability of K value. According to the comparison, K value, as the evaluation criteria in the rat skin anaphylactoid test, can more truly reflect the actual situation of skin aizen and minimize the error caused by animal individual factors. Compared with positive and negative two-level criteria for blue spot diameter, K value's positive, doubtable and negative three-level criteria are more objective and accurate. Therefore, K value can be used as the evaluation criteria in the rat skin anaphylactoid test.

A novel method of diffraction imaging flow cytometry for sizing microspheres.

We report a novel method of diffraction imaging flow cytometry to measure and analyze size distribution of microspheres. An automated and robust image processing software based on the short-time-Fourier-transform algorithm has been developed to analyze the characteristic and spatially varying oscillations of side scatters recorded as a diffraction image. Our results demonstrate that the new method allows accurate and rapid determination of single microspheres' diameters ranging from 1 to 100 µm. The capacity for analysis of light scattering by two-sphere aggregates has been demonstrated but analytical tools for characterization of aggregates by multiple microspheres remain to be developed.

[Effects of atorvastatin and CoQ(10) on myocardial energy metabolism in rabbits with hypercholesterolemia].

OBJECTIVE: To explore the interventional effects of atorvastatin and CoQ(10) on myocardial energy metabolism in rabbits with hypercholesterolemia. METHODS: Forty male New Zealand white rabbits were randomly divided into 5 groups: i.e. normal control, high cholesterol, statin, coenzyme Q(10) 1 and coenzyme Q(10) 2. After feeding for 6 weeks, the fasting blood samples were collected through ear marginal vein and the serum level of total cholesterol was determined. Myocardium was sampled for ultrastructures by electron microscopy; high-performance liquid chromatography (HPLC) was used to measure myocardial mitochondria adenosine triphosphate (ATP) and coenzyme CoQ(10). Ultraviolet spectrophotometry was used to measure the activities of mitochondrial complexes II and IV. RESULTS: In high cholesterol group, myocardial fibers were arrayed disorderly with partial rupture and dissolution. There was mitochondrial swelling with disorderly and fuzzy cristae. As compared with the controls, the activities of mitochondrial respiratory chain complexes II and IV declined (5.39 ± 0.53 vs 12.95 ± 0.99, 1.89 ± 0.26 vs 6.65 ± 0.95, P < 0.01), the contents of mitochondrial ATP and CoQ(10) decreased (0.17 ± 0.05 vs 0.44 ± 0.06, 0.09 ± 0.02 vs 0.25 ± 0.04, P < 0.01); for statin group versus high cholesterol group, the activities of mitochondrial respiratory chain complexes II and IV increased (9.12 ± 1.19 vs 5.39 ± 0.53, 4.61 ± 0.52 vs 1.89 ± 0.26, P < 0.01); the content differences of mitochondrial ATP and CoQ(10) were statistically insignificant. For CoQ(10) 1 group versus statin group, the differences of respiratory chain complexes II and IV were statistically insignificant; the contents of mitochondria ATP and CoQ(10) increased (0.35 ± 0.03 vs 0.16 ± 0.04, 0.17 ± 0.02 vs 0.07 ± 0.02, P < 0.01). For coenzyme Q(10) 2 group versus coenzyme Q(10) 1 group, none of the indices was statistically significant. CONCLUSION: High cholesterol can cause myocardial ultrastructural changes and impaired mitochondrial energy metabolism. Atorvastatin reduces the myocardial structural damage and the combination of atorvastatin and CoQ(10) may further improve the myocardial mitochondrial energy metabolism.

Prognostic significance of immunohistochemical expression of p53 gene product in operable breast cancer.

PURPOSE: The aim of this study was to investigate the prognostic significance of the expression of p53 gene product in operable invasive breast cancer by performing immunohistochemical analysis. MATERIALS AND METHODS: Between January 1993 and December 2001, 440 operable invasive breast cancer patients underwent immunohistochemical staining for p53, and we retrospectively analyzed these results together with the clinical outcomes. RESULTS: The overexpression of p53 was detected in 51.6% of the cases. The overexpression of p53 was inversely correlated with lymph node metastasis (p=0.005). The tumor size, tumor histology, histologic grade, hormonal receptor status and tumor stage were not related to the overexpression of p53. Multivariate Cox regression analysis indicate that lymph node metastasis, tumor size and the p53 expression were the significant prognostic factors for overall survival; lymph node metastasis, the estrogen receptor status and the p53 expression were the significant prognostic factors for relapse free survival. On the subgroup analysis, the p53 non-expressors showed better 7-year overall survival (92.7% vs. 76.7%, respectively, p=0.011) and relapse free survival (74.9% vs. 57.8%, respectively, p=0.032) than did the p53 overexpressors for the patients with lymph node metastasis. However, for the patients without lymph node metastasis, the survival rates were not different for both the p53 non-expressors and the p53 overexpressors. CONCLUSION: Immunohistochemical staining of the p53 gene product was an independent prognostic factor for predicting survival of the lymph node positive invasive breast cancer patients.

Prognostic Significance of Immunohistochemical Expression of p53 Gene Product in Operable Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The aim of this study was to investigate the prognostic significance of the expression of p53 gene product in operable invasive breast cancer by performing immunohistochemical analysis. MATERIALS AND METHODS: Between January 1993 and December 2001, 440 operable invasive breast cancer patients underwent immunohistochemical staining for p53, and we retrospectively analyzed these results together with the clinical outcomes. RESULTS: The overexpression of p53 was detected in 51.6% of the cases. The overexpression of p53 was inversely correlated with lymph node metastasis (p=0.005). The tumor size, tumor histology, histologic grade, hormonal receptor status and tumor stage were not related to the overexpression of p53. Multivariate Cox regression analysis indicate that lymph node metastasis, tumor size and the p53 expression were the significant prognostic factors for overall survival; lymph node metastasis, the estrogen receptor status and the p53 expression were the significant prognostic factors for relapse free survival. On the subgroup analysis, the p53 non-expressors showed better 7-year overall survival (92.7% vs. 76.7%, respectively, p=0.011) and relapse free survival (74.9% vs. 57.8%, respectively, p=0.032) than did the p53 overexpressors for the patients with lymph node metastasis. However, for the patients without lymph node metastasis, the survival rates were not different for both the p53 non-expressors and the p53 overexpressors. CONCLUSION: Immunohistochemical staining of the p53 gene product was an independent prognostic factor for predicting survival of the lymph node positive invasive breast cancer patients.

[The effect of captopril and valsartan on preventing the formation of atherosclerotic plaque].

OBJECTIVE: To observe the effect of captopril and valsartan on preventing the formation of atherosclerosis plaque in rabbit atherosclerotic models. METHODS: The atherosclerotic models of rabbits fed with high-cholesterol diet were used. There were four groups: high cholesterol group, high cholesterol + captopril group, high cholesterol + valsartan group, normal food group. The intima-media thickness in abdominal aortic were measured by ultrasound. The pathogenic features of the arterial walls were showed by HE stain and observed by light microscope. RESULTS: There were less atherosclerotic plaque in high cholesterol + captopril group and high cholesterol + valsartan group than in cholesterol group. The intima-media thickness in high cholesterol + captopril group and in high cholesterol + valsartan group were much more decreased than in high cholesterol group (0.05 +/- 0.005, 0.05 +/- 0.007 vs 0.07 +/- 0.100, P < 0.01). The connection of the endothelial cells were less damaged in high cholesterol + captopril group and high cholesterol + valsartan group than in high cholesterol group. CONCLUSIONS: Ti is true that angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) have the effect of preventing or decreasing the formation of atherosclerotic plaque in arterial wall. The findings suggest that ACEI and/or ARB should be first chosen for those with hypertension and with atherosclerotic risk factors or atherosclerotic diseases.