Parathyroid hormone related-protein (PTHrP) in tissues with poor prognosis in prostate cancer patients.

BACKGROUND: Parathyroid hormone-related peptide (PTHrP) is known to have a pivotal role in the progression of various solid tumors, among which prostate cancer stands out. However, the extent of PTHrP expression and its clinical implications in prostate cancer patients remain shrouded in obscurity. The primary objective of this research endeavor was to shed light on the relevance of PTHrP in the context of prostate cancer patients and to uncover the potential underlying mechanisms. METHODS: The expression of PTHrP, E-cadherin, and vimentin in tumor tissues of 88 prostate cancer patients was evaluated by immunohistochemical technique. Subsequently, the associations between PTHrP and clinicopathological parameters and prognosis of patients with prostate cancer were analyzed. RESULTS: Immunohistochemical analysis showed that the expression rates of PTHrP, E-cadherin, and vimentin in prostate cancer tissues were 95.5%, 88.6%, and 84.1%, respectively. Patients with a high level of PTHrP had a decreased expression of E-cadherin (P = .013) and an increased expression of vimentin (P = .010) compared with patients with a low level of PTHrP. Besides, the high expression of PTHrP was significantly correlated with a higher level of initial prostate-specific antigen (P = .026), positive lymph node metastasis (P = .010), osseous metastasis (P = .004), and Gleason score (P = .026). Moreover, patients with a high level of PTHrP had shorter progression-free survival (P = .002) than patients with a low level of PTHrP. CONCLUSION: The present study indicates that PTHrP is associated with risk factors of poor outcomes in prostate cancer, while epithelial-mesenchymal transition may be involved in this process.

Construction of an individualized clinical prognostic index based on ubiquitination-associated lncRNA in clear cell renal cell carcinoma patients.

BACKGROUND: ccRCC is considered as the main subtype of RCC, which accounted for sixth deadliest cancer worldwide. Recently, ubiquitination has been reported to be closely involved in the progression of tumore. The purpose of this study was to identify the ubiquitination-associated genes and co-expressed lncRNAs on the prognosis of clear cell renal cell carcinoma (ccRCC) patients. METHODS AND PATIENTS: We downloaded 530 cases and the corresponding transcriptome profiling from The Cancer Genome Atlas (TCGA) database. We distinguished mRNA and lncRNA expression data from the transcriptome profiling and then extracted the expression of mRNAs that regulate protein ubiquitination. We obtained lncRNAs associated with protein ubiquitination regulation from the lncRNA data by gene co-expression analysis. Cox regression analysis of survival time, survival status, and lncRNA expression level was carried out, and a prognostic index (PI) was constructed. RESULTS: The PI was established based on 8 prognostic lncRNAs that regulate protein ubiquitination and distinguish the high-risk group patients from all patients. Multivariate analysis indicated that this PI was an individualized clinical prognostic factor for patients with ccRCC. Regarding clinical characteristics, a ubiquitination-associated clinical-prognostic index (UCPI), containing 8 ubiquitination-related lncRNAs and age, was established and tested with AUC of 0.80. CONCLUSION: We established a UCPI containing 8 lncRNAs related to protein ubiquitination. This UCPI may become an appropriate model to predict the prognosis in ccRCC patients and guide clinicians to adjust the follow-up regimen.

Targeting HNRNPU to overcome cisplatin resistance in bladder cancer.

PURPOSE: The overall response of cisplatin-based chemotherapy in bladder urothelial carcinoma (BUC) remains unsatisfactory due to the complex pathological subtypes, genomic difference, and drug resistance. The genes that associated with cisplatin resistance remain unclear. Herein, we aimed to identify the cisplatin resistance associated genes in BUC. EXPERIMENTAL DESIGN: The cytotoxicity of cisplatin was evaluated in six bladder cancer cell lines to compare their responses to cisplatin. The T24 cancer cells exhibited the lowest sensitivity to cisplatin and was therefore selected to explore the mechanisms of drug resistance. We performed genome-wide CRISPR screening in T24 cancer cells in vitro, and identified that the gene heterogeneous nuclear ribonucleoprotein U (HNRNPU) was the top candidate gene related to cisplatin resistance. Epigenetic and transcriptional profiles of HNRNPU-depleted cells after cisplatin treatment were analyzed to investigate the relationship between HNRNPU and cisplatin resistance. In vivo experiments were also performed to demonstrate the function of HNRNPU depletion in cisplatin sensitivity. RESULTS: Significant correlation was found between HNRNPU expression level and sensitivity to cisplatin in bladder cancer cell lines. In the high HNRNPU expressing T24 cancer cells, knockout of HNRNPU inhibited cell proliferation, invasion, and migration. In addition, loss of HNRNPU promoted apoptosis and S-phase arrest in the T24 cells treated with cisplatin. Data from The Cancer Genome Atlas (TCGA) demonstrated that HNRNPU expression was significantly higher in tumor tissues than in normal tissues. High HNRNPU level was negatively correlated with patient survival. Transcriptomic profiling analysis showed that knockout of HNRNPU enhanced cisplatin sensitivity by regulating DNA damage repair genes. Furthermore, it was found that HNRNPU regulates chemosensitivity by affecting the expression of neurofibromin 1 (NF1). CONCLUSIONS: Our study demonstrated that HNRNPU expression is associated with cisplatin sensitivity in bladder urothelial carcinoma cells. Inhibition of HNRNPU could be a potential therapy for cisplatin-resistant bladder cancer.

lncRNA MORT Regulates Bladder Cancer Behaviors by Downregulating MicroRNA-146a-5p.

BACKGROUND: Long noncoding RNAs (lncRNAs) are involved in the progression of various cancers. lncRNA MORT is downregulated in bladder cancer, while its function in this disease is unknown. METHODS: lncRNA MORT and miR-146a-5p expression in 56 bladder cancer patients was detected by RT-qPCR. Correlations between MORT and miR-146a-5p were analyzed by Pearson's correlation coefficient. CCK-8 and flow transwell assays were applied to examine the behavioral changes in HT-1197 and HT-1376. RESULTS: We found that miR-146a-5p was upregulated, while lncRNA MORT was downregulated in bladder cancer. miR-146a-5p and MORT were inversely and significantly correlated in tumor tissues. Overexpression of miR-146a-5p promoted, while overexpression of lncRNA MORT inhibited the invasion, migration, and proliferation of cells of bladder cancer cell lines. In addition, overexpression of lncRNA MORT inhibited miR-146a-5p; miR-146a-5p overexpression failed to significantly affect lncRNA MORT expression but attenuated its inhibitory effects on cancer cell behaviors. CONCLUSION: lncRNA MORT may regulate bladder cancer cell behaviors by downregulating miR-146a-5p.

Two new triterpenoid saponins derived from the leaves of Panax ginseng and their antiinflammatory activity.

BACKGROUND: The leaves and roots of Panax ginseng are rich in ginsenosides. However, the chemical compositions of the leaves and roots of P. ginseng differ, resulting in different medicinal functions. In recent years, the aerial parts of members of the Panax genus have received great attention from natural product chemists as producers of bioactive ginsenosides. The aim of this study was the isolation and structural elucidation of novel, minor ginsenosides in the leaves of P. ginseng and evaluation of their antiinflammatory activity in vitro. METHODS: Various chromatographic techniques were applied to obtain pure individual compounds, and their structures were determined by nuclear magnetic resonance and high-resolution mass spectrometry, as well as chemical methods. The antiinflammatory effect of the new compounds was evaluated on lipopolysaccharide-stimulated RAW 264.7 cells. RESULTS AND CONCLUSIONS: Two novel, minor triterpenoid saponins, ginsenoside LS1 (1) and 5,6-didehydroginsenoside Rg3 (2), were isolated from the leaves of P. ginseng. The isolated compounds 1 and 2 were assayed for their inhibitory effect on nitric oxide production in LPS-stimulated RAW 264.7 cells, and Compound 2 showed a significant inhibitory effect with IC50 of 37.38 µM compared with that of NG-monomethyl-L-arginine (IC50 = 90.76 µM). Moreover, Compound 2 significantly decreased secretion of cytokines such as prostaglandin E2 and tumor necrosis factor-α. In addition, Compound 2 significantly suppressed protein expression of inducible nitric oxide synthase and cyclooxygenase-2. These results suggested that Compound 2 could be used as a valuable candidate for medicinal use or functional food, and the mechanism is warranted for further exploration.

Increased UCP1 expression in the perirenal adipose tissue of patients with renal cell carcinoma.

Perirenal adipose tissue (PAT) has been implicated in renal cell carcinoma (RCC). The expression of uncoupling protein 1 (UCP1) is higher in PAT compared with that in back subcutaneous adipose tissue (bSAT). The aim of the present study was to determine UCP1 expression in different parts of PAT and to analyze the correlation between UCP1 expression in PAT and RCC. PAT from the upper and lower renal poles and bSAT samples were collected from 50 patients with RCC (RCC group) and 54 patients with renal cysts (control group) who had undergone renal surgery. Both UCP1 mRNA and protein levels were found to be significantly higher and adipocytes appeared to be smaller in the PAT of the RCC group. Furthermore, the RCC group had more multilocular UCP1­positive adipocytes. UCP1 staining in the PAT was significantly stronger in the RCC group, but there was no significant difference in UCP1 staining in the bSAT between the two groups. Furthermore, Fuhrman grade and T stage were higher in the high UCP1 expression group of RCC patients. In conclusion, high UCP1 expression in the PAT may serve as an indicator of poor prognosis in RCC.

MR urethrography versus X-ray urethrography compared with operative findings for the evaluation of urethral strictures.

PURPOSE: We compared the accuracy of magnetic resonance (MR) urethrography and X-ray urethrography with operative findings for urethral strictures and observed their effects on treatment. MATERIALS AND METHODS: A total of 87 male patients (10-85 years of age) treated from January 2015 to December 2016 were included in the study. X-ray and MR urethrograms were performed for all patients to determine the location, length, and degree of urethral strictures and the organizational structure around the urethra, and the results were compared with the operative findings. One-way analysis of variance (ANOVA) was performed to compare the lengths of the urethral strictures determined by the two methods with the operative findings. A value of P < 0.05, calculated using GraphPad software, indicated statistical significance. RESULTS: Urethral stricture was more clearly shown on MR urethrography than on X-ray urethrography. The stricture length measured by conventional X-ray urethrography [(2.17 ± 0.65) cm] was much longer than that measured by MR urethrography [(1.68 ± 0.67) cm]. The surgical findings [(1.66 ± 0.70) cm] were significantly different from X-ray urethrography findings (F = 24.660, P = 0.000), but no significant difference was observed between the surgical findings and the stricture length measured by MR urethrography (F = 0.040, P = 0.842). CONCLUSION: Urethral strictures can be displayed more clearly and accurately by MR urethrography than by X-ray urethrography. MR urethrography is expected to become a necessary and standard procedure for the preoperative examination of urethral strictures.

[Inhibin B level helps evaluate the testicular function of prepubertal patients with varicocele].

OBJECTIVE: To investigate the role of the serum inhibin B (INHB) level in evaluating the testicular function of the prepubertal patient with varicocele (VC) after high ligation of the spermatic vein (HLSV). METHODS: This study included 31 prepubertal male patients with left VC, averaging 12.55 years of age and 9 complicated by right VC. We collected peripheral blood samples before and at 4, 12 and 26 weeks after HLSV as well as spermatic venous blood samples intraoperatively for determination of the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), anti-sperm antibody (AsAb) and serum INHB by ELISA. RESULTS: Compared with the baseline, statistically significant differences were observed in the INHB level in the peripheral blood at 12 and 26 weeks after operation (ï¼»255.18 ± 69.97ï¼½ vs ï¼»141.78 ± 59.82ï¼½ pg/ml, P < 0.05) and that in the spermatic venous blood intraoperatively (ï¼»255.18 ± 69.97ï¼½ vs ï¼»412.44 ± 259.42ï¼½ pg/ml, P < 0.01). Spearman's analysis showed a negative correlation between the level of INHB and that of FSH (r = －0.224, P < 0.01). CONCLUSIONS: The level of serum INHB in the peripheral blood of the prepubertal VC patient is decreased within 6 months after HLSV and negatively correlated with that of FSH. The levels of INHB and FSH may well reflect the testicular function of the prepubertal VC patient.

MicroRNA-590-5p regulates cell viability, apoptosis, migration and invasion of renal cell carcinoma cell lines through targeting ARHGAP24.

Renal cell carcinoma (RCC) is the leading cause of death in renal malignancies. MicroRNA-590-5p (miR-590-5p) is of great importance in the processes of many cancers regarding regulation of cancer cell invasion and proliferation. In our study, alternation of miR-590-5p expression in RCC cell lines through transfection with pre-miR-590-5p (up-regulation) or anti-miR-590-5p (down-regulation) was performed. Apoptosis and viability of RCC cell lines were measured by flow cytometry and CCK-8 analysis, respectively. Cell invasion and migration were estimated by Transwell assay. The association of miR-590-5p with ARHGAP24 expression was evaluated using luciferase assays, real-time PCR and western blot assay. The expressions of apoptosis and migration-related protein were also measured by western blotting. We found that pre-miR-590-5p transfection in Caki-2 and 786-O cells showed significant increases in cell viability, invasion and migration, which were accompanied by decreased cell apoptosis, while anti-miR-590-5p transfection obviously inhibited the cell viability, migration and invasion of Caki-2 and 786-O cells as well as induced apoptosis, compared with the negative control group. Furthermore, bioinformatics combined with luciferase reporter assays indicated that ARHGAP24 is directly targeted by miR-590-5p. ARHGAP24 overexpression in 786-O and Caki-2 cells phenocopied the effects of anti-miR-590-5p transfection along with enhanced expression of active Caspase-3 and Bax/Bcl-2 ratio as well as decreased expression of MMP-2 and MMP-9. These findings suggested that miR-590-5p/ARHGAP24 seems to function as a potentially beneficial target for RCC treatment.

Comparison of the efficacy and safety of URSL, RPLU, and MPCNL for treatment of large upper impacted ureteral stones: a randomized controlled trial.

BACKGROUND: There are three minimally invasive methods for the management of large upper impacted ureteral stones: mini-percutaneous nephrolithotomy (MPCNL), transurethral ureteroscope lithotripsy (URSL), and retroperitoneal laparoscopic ureterolithotomy (RPLU). This study aimed to compare MPCNL, URSL, and RPLU, and to evaluate which one is the best choice for large upper impacted ureteral stones. METHODS: Between January 2012 and December 2015, at the Department of Urology, Huai'an First People's Hospital, 150 consecutively enrolled patients with a large upper impacted ureteral stone (>15 mm) were included. The patients were randomly divided (1:1:1) into the MPCNL, URSL, and RPLU groups. The primary endpoint was success of stone removal measured 1 month postoperatively and the secondary endpoints were intraoperative and postoperative parameters and complications. RESULTS: Fifteen patients needed auxiliary ESWL after URSL, and 3 patients after MPCNL, but none after RPLU. The stone clearance rate was 96% (48/50) in the MPCNL group and 72% (33/46) in the URSL group. In the RPLU group the stones were completely removed and the stone clearance rate was 100% (48/48) (P = 0.021 vs. URSL; P = 0.083 vs. MPCNL). Operation-related complications were similar among the three groups (all P > 0.05). Hospital stay was shorter in the URSL group compared with MPCNL (P = 0.003). Operation time was the shortest with URSL and the longest with MPCNL (all P < 0.05). CONCLUSIONS: MPCNL and RPUL are more suitable for upper ureteral impacted stones of >15 mm. URSL could be considered if the patient is not suitable for general anesthesia, or the patient requests transurethral uretroscopic surgery. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry (Registration number: ChiCTR-INR-17011507 ; Registration date: 2017-5-22).

Polysaccharide from wheat bran induces cytokine expression via the toll-like receptor 4-mediated p38 MAPK signaling pathway and prevents cyclophosphamide-induced immunosuppression in mice.

Wheat bran-derived polysaccharides have attracted particular attention due to their immunomodulatory effects. However, the molecular mechanisms underlying their functions are poorly understood. The current study was designed to examine the effect of wheat bran polysaccharide (WBP) on RAW 264.7 cells and the underlying signaling pathways, which have not been explored. In addition, we also investigated the immuno-enhancement effects of WBP on cyclophosphamide (CTX)-induced immunosuppression in mice. WBP significantly increased the concentrations of intracellular nitric oxide (NO) and cytokines such as prostaglandin E2 (PGE2) and tumor necrosis factor-α (TNF-α) in RAW 264.7 cells. The result of RT-PCR analysis indicated that WBP also enhanced inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-α expression. Further analyses demonstrated that WBP rapidly activated phosphorylated p38 mitogen-activated protein kinase (MAPK) and the transcriptional activities of activator protein-1 (AP-1) and nuclear factor (NF)-κB via toll-like receptor 4 (TLR4). Furthermore, in vivo experiments revealed that WBP increased the spleen and thymus indices significantly, and markedly promoted the production of the serum cytokines IL-2 and IFN-γ in CTX-induced immunosuppressed mice. Taken together, these results suggest that WBP can improve immunity by enhancing immune function, and could be explored as a potential immunomodulatory agent in functional food.

Inhibitory member of the apoptosis-stimulating protein of p53 is overexpressed in bladder cancer and correlated to its progression.

Several lines of direct evidence show that inhibitory member of the apoptosis-stimulating protein of p53 (iASPP) has an important function in cancer progression. However, its expression pattern and relationship with clinical pathologic characteristics in bladder cancer (BC) have not been completely elucidated. In this study, firstly, samples from 3 patients with invasive BC were detected by liquid chromatography tandem mass spectrometry to confirm overexpression of iASPP in BC, then samples from patients with noninvasive and invasive BC were detected by real-time polymerase chain reaction, Western blot, and tissue microarry immunohistochemistry. The relationship between iASPP expression and various clinicopathological features was investigated. The results showed m-RNA and protein of iASPP were overexpressed in BC and the rate of iASPP-positive cells was positively correlated with Union for International Cancer Control-Tumor, Node, Metastases stage, histologic grade, lymph node metastasis and poor overall survive. The data demonstrate that iASPP is overexpressed in BC and promotes the malignancy of BC. iASPP maybe serve as a potential therapeutic target for BC.

miR-143 inhibits bladder cancer cell proliferation and enhances their sensitivity to gemcitabine by repressing IGF-1R signaling.

microRNAs (miRNAs) are a class of small RNAs that regulate gene expression. It has been demonstrated that aberrant miRNA expression is associated with cancer development and carcinogenesis. Altered miRNA expression has been suggested to occur in bladder cancer. In other cancer systems, studies have indicated that miR-143, as a tumor suppressor gene, plays essential roles in cancer progression. However, its role in bladder cancer has yet to be elucidated. In the present study, we observed that miR-143 expression was downregulated in human bladder cancer tissues and cells, and that its levels were negatively correlated with bladder cancer clinical stages. We further demonstrated that insulin-like growth factor-1 receptor (IGF-1R) is a functional target of miR-143. Their expression levels were inversely correlated in bladder cancer samples. Overexpression of miR-143 inhibited cell proliferation and promoted chemosensitivity of bladder cancer 5637 cells to gemcitabine. Consistently, small interfering RNA-mediated knockdown of IGF-1R phenocopied miR-143 overexpression. Notably, the expression of IGF-1R is a predictor of patient prognosis. Collectively, our findings indicate that miR-143 is a valuable biomarker for bladder cancer. The miR-143/IGF-1R axis is associated with bladder cancer drug resistance and patient survival.

High neutrophil-to-lymphocyte ratio is associated with increased carotid artery intima-media thickness in type 2 diabetes.

AIMS/INTRODUCTION: Emerging evidence suggests that the neutrophil-to-lymphocyte ratio (NLR) is a novel potential marker of inflammatory responses. The objective was to evaluate the association between NLR and carotid artery intima-media thickness (cIMT) in type 2 diabetes. MATERIALS AND METHODS: We carried out a case-control study involving 320 patients with type 2 diabetes, and 250 age-, sex- and body mass index-matched healthy controls who all underwent carotid ultrasonography and took a blood examination. We divided the diabetes patients into two groups according to cIMT: 188 diabetes patients with high cIMT and 132 diabetes patients with low cIMT, and compared baseline characteristics and NLR between the two groups and healthy controls. RESULTS: The mean NLR was significantly higher in the group of diabetes patients with high cIMT than the group of diabetes patients with low cIMT, who in turn showed a significantly higher NLR compared with control participants. Logistic regression analysis showed that the NLR was an independent risk factor for diabetes patients with high cIMT (odds ratio 140.89, 95% CI 1.71-11615.30, P = 0.028). Based on the receiver operating characteristic curve, use of the NLR as an indicator for diabetes patients with high cIMT diagnosis was projected to be 3.16, and yielded a sensitivity and specificity of 36.2% and 93.2%, respectively, with an area under the curve of 0.606 (95% CI 0.544-0.667). CONCLUSIONS: High NLR might be a potential biomarker for the increased cIMT in type 2 diabetes patients. Future studies are required to validate our findings.

Anti-Inflammatory Effects of Chloranthalactone B in LPS-Stimulated RAW264.7 Cells.

Chloranthalactone B (CTB), a lindenane-type sesquiterpenoid, was obtained from the Chinese medicinal herb Sarcandra glabra, which is frequently used as a remedy for inflammatory diseases. However, the anti-inflammatory mechanisms of CTB have not been fully elucidated. In this study, we investigated the molecular mechanisms underlying these effects in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. CTB strongly inhibited the production of nitric oxide and pro-inflammatory mediators such as prostaglandin E2, tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), and IL-6 in RAW264.7 cells stimulated with LPS. A reverse-transcription polymerase chain reaction assay and Western blot further confirmed that CTB inhibited the expression of inducible nitric oxide synthase, cyclooxygenase-2, TNF-α, and IL-1ß at the transcriptional level, and decreased the luciferase activities of activator protein (AP)-1 reporter promoters. These data suggest that inhibition occurred at the transcriptional level. In addition, CTB blocked the activation of p38 mitogen-activated protein kinase (MAPK) but not c-Jun N-terminal kinase or extracellular signal-regulated kinase 1/2. Furthermore, CTB suppressed the phosphorylation of MKK3/6 by targeting the binding sites via formation of hydrogen bonds. Our findings clearly show that CTB inhibits the production of inflammatory mediators by inhibiting the AP-1 and p38 MAPK pathways. Therefore, CTB could potentially be used as an anti-inflammatory agent.

LINC00312 inhibits the migration and invasion of bladder cancer cells by targeting miR-197-3p.

To investigate the influence of the long non-coding RNA LINC00312 on bladder cancer (BC) cell invasion and metastasis by targeting miR-197-3p. BC and corresponding adjacent tissues were collected. LINC00312 and miR-197-3p were measured, and their correlation was detected through quantitative real-time PCR (qRT-PCR). BC cell line T24 was transfected and grouped (five groups) according to different transfection conditions. A scratch test was applied to analyze cell migration, and a Transwell assay was used to test cell invasion ability. Western blotting was to measure matrix metalloproteinase (MMP)-2, MMP-9, and the tissue inhibitor of metalloproteinase 2 (TIMP2) protein levels. qRT-PCR indicated that LINC00312 expression was lower but miR-197-3p expression was higher in BC tissues compared with adjacent tissues; LINC00312 was negatively correlated with miR-197-3p. The migration test revealed that the downregulation of miR-197-3p and overexpression of LINC00312 inhibited cell migration and invasion abilities, while the overexpression of miR-197-3p and the upregulation of LINC00312 promoted cell migration and invasion. BC cells with downregulated miR-197-3p or upregulated LINC00312 had low MMP-2 and MMP-9 levels but high TIMP2. LINC00312 inhibited BC cell invasion and metastasis through mediating miR-197-3p.

The dichloromethane fraction from Mahonia bealei (Fort.) Carr. leaves exerts an anti-inflammatory effect both in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Mahonia bealei has a long history of medical use in traditional Chinese medicine for the treatment of inflammatory-associated diseases. Despite numerous phytochemical and pharmacological studies, there is a lack of systematic studies to understand the cellular and molecular mechanisms of the anti-inflammatory activity of this plant. AIM OF STUDY: This study aimed to evaluate the anti-inflammatory activity of the dichloromethane fraction from M. bealei leaves (MBL-CH). MATERIALS AND METHODS: RAW 264.7 cells were pretreated with different concentrations of MBL-CH for 30min prior to treatment with 1µg/ml of lipopolysaccharide (LPS). The nuclear factor κB (NF-κB) pathway and subsequent production of inflammatory mediators, such as nitric oxide (NO), prostaglandin E2 (PGE2), and tumour necrosis factor (TNF)-α were investigated. Furthermore, the in vivo mouse model of LPS-induced acute lung injury (ALI) was employed to study the anti-inflammatory effects of MBL-CH. RESULTS: Pre-treatment with MBL-CH significantly inhibited the LPS-stimulated secretion of NO, PGE2, and TNF-α into the culture medium, as well as the mRNA levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-α, which were associated with a reduction in the phosphorylation of IκBα, Akt, and PI3K and inhibition of the transcriptional activity of NF-κB. Furthermore, in vivo experiments revealed that MBL-CH attenuated LPS-stimulated lung inflammation in mice. CONCLUSION: Taken together, our findings indicate that MBL-CH attenuates LPS-stimulated inflammatory responses in macrophages by blocking NF-κB activation through interference with activation of the PI3K/Akt pathway, providing scientific evidence that the plant can be employed in traditional remedies.

Therapy to target renal cell carcinoma using 131I-labeled B7-H3 monoclonal antibody.

B7-H3 is a tumor-associated antigen that plays a critical role in potential tumor-targeted therapy. In this study, we aimed to assess the radiobiological effect of 131I-labeled B7-H3 monoclonal antibody (131I-4H7) in nude mice with human renal cell carcinoma (RCC) and evaluate the effect of 131I-4H7 on RCC treatment. The radiobiological activity and tumor uptake of 131I-4H7, and its effect on tumor growth were measured. 131I-4H7 was absorbed by the tumor and reached its maximal uptake rate (3.32% injected dose [ID]/g) at 24 h, at which point the drug concentration in the tumor was 7.36-, 2.06-, 1.80-, and 2.78-fold higher than that in muscle, kidneys, liver, and heart, respectively. Measurements and positron emission tomography-computed tomography imaging showed that tumor development was significantly inhibited by 131I-4H7. HE staining revealed that 131I-4H7 significantly injures tumor cells. Our results suggest that 131I-4H7 is markedly absorbed by the tumor and did suppress the development of RCC xenografted tumors in nude mice, which might provide a new candidate for antibody-mediated targeted radiotherapy in human RCC.

Apigenin-7-O-ß-D-glucuronide inhibits LPS-induced inflammation through the inactivation of AP-1 and MAPK signaling pathways in RAW 264.7 macrophages and protects mice against endotoxin shock.

Apigenin-7-O-ß-D-glucuronide (AG), an active flavonoid derivative isolated from the agricultural residue of Juglans sigillata fruit husks, possesses multiple pharmacological activities, including anti-oxidant, anti-complement, and aldose reductase inhibitory activities. To date, no report has identified the anti-inflammatory mechanisms of AG. This study was therefore designed to characterize the molecular mechanisms of AG on lipopolysaccharide (LPS)-induced inflammatory cytokines in RAW 264.7 cells and on endotoxin-induced shock in mice. AG suppressed the release of nitric oxide (NO), prostaglandin E2 (PGE2), and tumour necrosis factor-α (TNF-α) in LPS-stimulated RAW 264.7 macrophages in a dose-dependent manner without affecting cell viability. Additionally, AG suppressed LPS-induced mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and TNF-α. AG treatment decreased the translocation of c-Jun into the nucleus, and decreased activator protein-1 (AP-1)-mediated luciferase activity through the inhibition of both p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) phosphorylation. Consistent with the in vitro observations, AG protected mice from LPS-induced endotoxin shock by inhibiting proinflammatory cytokine production. Taken together, these results suggest that AG may be used as a source of anti-inflammatory agents as well as a dietary complement for health promotion.

Determination of UCP1 expression in subcutaneous and perirenal adipose tissues of patients with hypertension.

The objective of this study is to determine the property of human perirenal adipose tissue (PAT) and assess the adipose property of PAT in hypertension. Ninety-four patients, including 64 normotensive patients (T-NP) and 30 hypertensive patients (HP), who underwent renal surgery were included. Expression analysis was performed using quantitative real-time polymerase chain reaction, Western blot, and immunohistochemistry in PAT and back subcutaneous adipose tissue (bSAT) depots. Compared with bSAT, PAT adipocytes were smaller, and the expressions of uncoupling protein-1 (UCP1) mRNA and protein were markedly higher, while the mRNA expressions of markers for classic beige and white adipocytes were lower in PAT. Immunohistochemistry analysis showed more multilocular UCP1-positive adipocytes in PAT than in bSAT. UCP1 expressions were lower in PAT in HP than in the T-NP or age- and body mass index-matched NP groups. Bigger unilocular adipocytes with less UCP1 staining in PAT were detected in HP than in NP group, although no such difference was observed in bSAT. PAT acts as a brown-like fat. UCP1 expression of PAT was lower in HP than in normotensive patients. UCP1 expression of PAT may serve as a protective indicator for hypertension.