Dendrocandin U from Dendrobium officinale Kimura et Migo Inhibits M1 Polarization in Alveolar Macrophage by Suppressing NF-κB Signaling Pathway.

Dendrobium officinale Kimura et Migo is a valuable and homologous medicine and food traditional Chinese medicine. Currently there are few studies on the anti-inflammatory activity of lipophilic components. The aim of this study was to explore the anti-inflammatory effect and mechanism of the lipophilic compounds in Dendrobium officinale. Six compounds were isolated and identified, including three bibenzyl compounds, dendrocandin U, dendronbibisline B, erianin, and three lignans, (-)-syringaresinol, (+)-syringaresinol-O-ß-D-glucopyranoside, 5-methoxy-(+)-isolariciresinol. Among them, dendronbibisline B and 5-methoxy-(+)-isolariciresinol were isolated from Dendrobium officinale for the first time. Besides, we found dendrocandin U, dendronbibisline B and (-)-syringaresinol exhibited the anti-inflammation to inhibit nitric oxide secretion induced by lipopolysaccharide (LPS)/interferon (IFN-γ) in MH-S cells. Furthermore, dendrocandin U could inhibit the expression of tumor necrosis factor-α (TNF-α), Cluster of Differentiation 86 (CD86), and reduce inflammatory morphological changes of macrophages. Meanwhile, we confirmed that the anti-inflammation mechanism of dendrocandin U was to inhibit M1 polarization by suppressing toll-like receptor 4 (TLR4)/recombinant myeloid differentiation factor 88 (MyD88)/nuclear factor kappa B (NF-κB) signaling pathway. In this paper, dendrocandin U with significant anti-inflammatory activity was found from Dendrobium officinale, which could provide a basis for the study of its anti-inflammatory drugs.

The impact of atrial fibrillation on outcomes in patients undergoing radical prostatectomy.

PURPOSE: To assess the role of atrial fibrillation (AF) on complicating inpatient outcomes of radical prostatectomy (RP). MATERIALS AND METHODS: We identified patients treated with RP during 2012-2014 within National Inpatient Sample (NIS) database. Length of stay, cost of hospitalization, and in-hospital complications were compared between patients with or without diagnosis of AF. Propensity score matching methods and multivariable regression analysis were used to adjust for potential confounders and a trend analysis was conducted. RESULTS: Patients with AF had a significantly longer hospital stay (coefficient 0.19, 95% CI 0.09-0.29, P < 0.001) and higher cost (coefficient 0.10, 95% CI 0.06-0.15, P < 0.001). Post-operative cardiac complications were significantly higher for patients with AF (OR 16.38, 95% CI 7.72-34.74, P < 0.001), while no differences were found in other complications between the two groups. Similar results were shown in propensity score matching methods. The cardiac complications after laparoscopic RP (OR: 37.71, 95% CI 1.85-768.73, P = 0.018) and open RP (OR: 16.78, 95% CI 1.41-199.51, P = 0.026) were significantly higher than robot-assisted RP (RARP) in patients with AF. The results of trend study indicated that postoperative cardiac complication rates showed a trend of decreasing year by year while the prevalence of AF was rising. CONCLUSIONS: Perioperative AF is associated with increased cardiac complications, longer hospital stay and higher cost in PCa patients undergoing RP. RARP may be a preferred choice for patients with AF. Attention should be paid to this special patient population. Reasonable pre-operative risk stratification and standardized management should be done to decrease perioperative complications.

Positive node burden rather than the number of removed nodes impacts survival in patients with node-positive prostate cancer.

BACKGROUND: The value of pelvic lymphadenectomy during radical prostatectomy (RP) remains controversial. This study aims to test the effects of the number of removed lymph nodes (RLN), positive nodes (pLN), and pLN ratio (pLNR) on cancer-specific survival (CSS) in patients with node-positive prostate cancer (PCa). METHODS: A total of 2458 patients with a greater than 5% probability of lymph node invasion according to the updated Briganti nomogram who harboured pathologically confirmed positive nodes in the Surveillance, Epidemiology, and End Results database between 2004 and 2015 were identified. Multivariable Cox regression with forward stepwise selection was performed to identify independent risk factors for CSS. Maximally selected rank statistics were used to determine the most informative cut-off value for pLN and pLNR. RESULTS: The median pLN counts and RLN in the study were two (interquartile range [IQR] 1- 3) and 18 (IQR 15-23), respectively. The RLN counts could not predict CSS, while the higher pLN and pLNR were associated with worse CSS (hazard ratio [HR], 1.11; p < 0.001 and HR, 1.01; p < 0.001, respectively). Patients with ≤ 2 pLN or pLNR ≤ 20% had significantly better CSS than those with pLN > 2 or pLNR > 20% (HR, 1.38 (1.08-1.77); p = 0.009; HR, 1.77 (1.41-2.22); p < 0.001, respectively). CONCLUSIONS: In patients with node-positive PCa, pelvic lymphadenectomy provides important information for staging, prognosis, and guiding after RP therapy; however, it does not play a therapeutic role. The pLN counts and pLNR were independent predictors of CSS.

Impact of different color fiber sleeves on beam hazards of 532-nm laser and vaporization efficiency.

The 532-nm laser has become increasingly popular for the treatment of urologic diseases. However, laser beam will pose significant hazards for the health of surgeons. In order to reduce beam hazards during surgery, we compared the beam hazards of laser fiber with black sleeves to the traditional fiber with transparent sleeves, and the vaporization efficiency. A total of 18 porcine kidney specimens were vaporized in normal saline at a room temperature under 532-nm laser delivered through a 760-µm core diameter side firing fiber. Two groups were divided according to the color of fiber sleeves: the transparent and the black. Each group was then divided into another three subgroups by laser power: the 80 W group, the 120 W group, and the 160 W group. The beam hazard was evaluated by light intensity measured in a sector area at a distance of 0 m, 0.5 m, and 1 m from the irradiation center. The vaporization efficiency was measured by the vaporization groove depth under the working power of 80 W, 120 W, and 160 W with a working distance of 5 mm and irradiation time of 10 s. The light intensity measured in the black fiber sleeve group is significantly lower than that in the transparent one (P < 0.01), regardless of the measuring distance (0 m, 0.5 m, and 1.0 m) and laser power (80 W, 120 W, and 160 W). No statistical difference was found on the vaporization efficiency between the groups protected by fiber sleeves of different colors (transparent/black, p > 0.05). Compared to the traditional transparent fiber sleeves, more beam hazards will be reduced in the operative region with the protection of black fiber sleeves, especially those from the irradiation center. The vaporization efficiency is not affected by the color of fiber sleeves. Such findings may offer a completely new idea for the protection of surgeons in surgeries with 532-nm lasers.

Schisandrin A ameliorates increased pulmonary capillary endothelial permeability accompanied with sepsis through inhibition of RhoA/ROCK1/MLC pathways.

BACKGROUND: Sepsis is a systemic inflammatory response, and vascular leakage associated with acute lung injury (ALI) is an important pathophysiological process during sepsis. Schisandrin A (SchA) is a bioactive lignan which has been reported to have the anti-inflammatory effects in many studies, while whether SchA can ameliorate ALI-related vascular leakage caused by sepsis is unknown. OBJECTIVE: To evaluate the role and the underlying mechanism of SchA in increase of pulmonary vascular permeability induced by sepsis. METHODS: The effect of SchA on pulmonary vascular permeability was examined in rat acute lung injury model. The effect of SchA on skin vascular permeability of mice was investigated through Miles assay. MTT assay was performed to detect the cell activity, and transwell assay was used to detect the effect of SchA on cell permeability. The effects of SchA on junction proteins and RhoA/ROCK1/MLC signaling pathway were manifested by immunofluorescence staining and western blot. RESULTS: The administration of SchA alleviated rat pulmonary endothelial dysfunction, relieved increased permeability in the mouse skin and HUVECs induced by lipopolysaccharide (LPS). Meanwhile, SchA inhibited the formation of stress fibers, reversed the decrease of expression of ZO-1 and VE-cadherin. Subsequent experiments confirmed that SchA inhibited RhoA/ROCK1/MLC canonical pathway in rat lungs and HUVECs induced by LPS. Moreover, overexpression of RhoA reversed the inhibitory effect of SchA in HUVECs, which suggested that SchA protected the pulmonary endothelial barrier by inhibiting RhoA/ROCK1/MLC pathway. CONCLUSION: In summary, our results indicate that SchA ameliorates the increase of pulmonary endothelial permeability induced by sepsis through inhibition of RhoA/ROCK1/MLC pathway, providing a potentially effective therapeutic strategy for sepsis.

Plasma pharmacokinetics and tissue distribution of bufotalin in mice following single-bolus injection and constant-rate infusion of bufotalin solution.

Bufotalin is one of the active antitumor components in Ch'an Su which is a widely used traditional Chinese medicine. However, there is insufficient information on the biopharmaceutical properties of bufotalin based on pharmacokinetic studies. To investigate the pharmacokinetics and tissue distribution of bufotalin, single-bolus injection and constant-rate infusion of bufotalin solution were performed in mice. After single intravenous administration, bufotalin was quickly distributed and eliminated from the plasma with a t1/2 of 28.6 min and an MRT of 14.7 min. Bufotalin concentrations in brain and lung were significantly higher than those in blood and other tissues at 30 min after dosing. The steady-state bufotalin plasma concentration and tissue distribution were determined using a novel constant-rate infusion device, and the distribution characteristics were similar to those of single-bolus injection. These results indicated that bufotalin could cross the blood-brain barrier and naturally target the lung. Bufotalin might be a promising antitumor candidate for lung cancer.

Comparison of Oncological Outcomes Between Radical Prostatectomy and Radiotherapy by Type of Radiotherapy in Elderly Prostate Cancer Patients.

OBJECTIVE: We aimed compare the oncologic outcomes of radical prostatectomy (RP) with those of external beam radiotherapy (EBRT), brachytherapy (BT), or EBRT + BT (EBBT) in elderly patients with localised prostate cancer (PCa). METHODS: Localised PCa patients aged ≥70 years who underwent RP, EBRT, BT, or EBBT between 2004 and 2016 were identified from the Surveillance, Epidemiology, and End Results database. Multivariable competing risks survival analyses were used to estimate prostate cancer-specific mortality (CSM) and other-cause mortality (OCM). Subgroup analyses according to risk categories were also conducted. RESULTS: Overall, 14057, 37712, 8383, and 5244 patients aged ≥70 years and treated with RP, EBRT, BT, and EBBT, respectively, were identified. In low- to intermediate-risk patients, there was no significant difference in CSM risk between RP and the other three radiotherapy modalities (all P > 0.05). The corresponding 10-year CSM rates for these patients were 1.2%, 2.3%, 2.0%, and 1.8%, respectively. In high-risk patients, EBRT was associated with a higher CSM than RP (P = 0.003), whereas there was no significant difference between RP and BT or RP and EBBT (all P > 0.05). The 10-year CSM rates of high-risk patients in the RP, EBRT, BT, and EBBT groups were 7.5%, 10.2%, 8.3%, and 7.6%, respectively. Regarding OCM, the risk was generally lower in RP than in the other three radiotherapy modalities (all P < 0.001). CONCLUSIONS: Among men aged ≥70 years with localised PCa, EBRT, BT, and EBBT offer cancer-specific outcomes similar to those of RP for individuals with low- to intermediate-risk disease. In patients with high-risk disease, EBBT had outcomes equally favourable to those of RP, but RP is more beneficial than EBRT. More high-quality trials are warranted to confirm and expand the present findings.

Cognitive magnetic resonance imaging-ultrasound fusion transperineal targeted biopsy combined with randomized biopsy in detection of prostate cancer.

BACKGROUND: Prostate cancer (PCa) is one of the most common cancers among men. Various strategies for targeted biopsy based on multiparametric magnetic resonance imaging (mp-MRI) have emerged, which may improve the accuracy of detecting clinically significant PCa in recent years. AIM: To investigate the diagnostic efficiency of a template for cognitive MRI-ultrasound fusion transperineal targeted plus randomized biopsy in detecting PCa. METHODS: Data from patients with an increasing prostate-specific antigen (PSA) level but less than 20 ng/mL and at least one lesion suspicious for PCa on MRI from December 2015 to June 2018 were retrospectively analyzed. All patients underwent cognitive fusion transperineal template-guided targeted biopsy followed by randomized biopsy outside the targeted area. A total of 127 patients with complete data were included in the final analysis. A multivariable logistic regression analysis was conducted, and a two-sided P < 0.05 was considered statistically significant. RESULTS: PCa was detected in 66 of 127 patients, and 56 cases presented clinically significant PCa. Cognitive fusion targeted biopsy alone detected 59/127 cases of PCa, specifically 52/59 cases with clinically significant PCa and 7/59 cases with clinically insignificant PCa. A randomized biopsy detected seven cases of PCa negative on targeted biopsy, and four cases had clinically significant PCa. PSA density (OR: 1.008, 95%CI: 1.003-1.012, P = 0.001; OR: 1.006, 95%CI: 1.002-1.010, P = 0.004) and Prostate Imaging-Reporting and Data System (PI-RADS) scores (both P < 0.001) were independently associated with the results of cognitive fusion targeted biopsy combined with randomized biopsy and targeted biopsy alone. CONCLUSION: This single-centered study proposed a feasible template for cognitive MRI-ultrasound fusion transperineal targeted plus randomized biopsy. Patients with higher PSAD and PI-RADS scores were more likely to be diagnosed with PCa.

[Oral cavity delivery system of unfractionated and low molecular weight heparin].

The difference between absorption of unfractionated heparin (UFH) and low molecular weight heparin (LMWH) after oral and oral cavity administration were studied respectively, and the compatible enhancer for oral cavity delivery system of both drugs was found. The LMWH and UFH films were prepared with two bioadhesive materials Carbopol and alginate sodium for oral cavity delivery. The activated partial thromboplastin time (APTT) was used to determine LMWH and UFH in plasma after oral, oral cavity and sc administration in rats. The results show that the enhancer (Labrasol) can increase the absorption of LMWH and UFH through oral cavity in rats but not obviously. The oral cavity iontophoretic delivery system is a useful method to improve the absorption of LMWH and UFH through oral cavity mucosa.

Comparing the Oncological Outcomes of Cryoablation vs. Radical Prostatectomy in Low-Intermediate Risk Localized Prostate Cancer.

Purpose: To compare the oncologic outcomes of cryoablation (CA) and radical prostatectomy (RP) in patients with low- and intermediate-risk localized prostate cancer (PCa). Materials and Methods: PCa patients who received CA or RP between 2004 and 2015 were identified from the Surveillance, Epidemiology, and End Results database. Multivariable Cox proportional hazard analysis was used to compare the prostate cancer-specific survival (CSS) and overall survival (OS). We conducted 1:3 propensity score matching and adjusted standardized mortality ratio weighting (SMRW) to balance the clinicopathological characteristics. Results: Ninety-seven thousand seven hundred eighty-three patients were identified after preliminary screening. After matching, the CA and RP groups included 1,942 and 5,826 patients and had median follow-up periods of 85 and 72 months, respectively. CA had lower CSS and OS rates (hazard ratio [HR], 2.07; P = 0.007; HR, 2.09; P < 0.001, respectively) than did RP, which was consistent in the SMRW model (CSM: HR, 2.66; P < 0.001; OS: HR, 2.29; P < 0.001). The 10-years CSS and OS for CA vs. RP were 98.1 vs. 99.2% and 61.3 vs. 79.9%, respectively. Conclusions: In patients with low- to intermediate-risk localized PCa, CA had lower CSS rates than did RP. However, the high 10-years CSS rates indicated that CA could be an option for those who are not RP candidates. Further high-quality trials are needed to confirm and expand our findings.

Preparation of albumin nanospheres loaded with gemcitabine and their cytotoxicity against BXPC-3 cells in vitro.

AIM: To optimize formulation methods for loading gemcitabine (GEM), the main drug against pancreatic cancer, into albumin nanoparticles for extended blood circulation and improved efficacy. METHODS: GEM was loaded into two sizes of disolvation-crosslinked bovine serum albumin nanoparticles, with a mean diameter of 109.7 nm and 405.6 nm, respectively, by co-precipitation (the direct method) and follow-up adsorption (the indirect method). The antitumor activities of the two nanoparticulate formulations, were evaluated according to their anti-proliferative effects on the human pancreatic cell line BXPC-3, which were assessed using the MTT assay. RESULTS: The two nanoparticulate formulations, created by direct co-precipitation and indirect adsorption, possessed smooth surfaces and high drug loading efficiencies, 83% and 93% at 11% and 13% drug loading, respectively. The two formulations released GEM for 8 and 12 h, respectively, and significantly improved anti-BXPC-3 proliferation effects, as compared with the GEM solution and the drug-free albumin particles. CONCLUSION: Co-precipitating and adsorbing GEM into albumin particles resulted in sustained-release nanoparticulate formulations with improved antitumor cytotoxicity. The result suggests that this is a useful formulation strategy for improving the antitumor efficacy of GEM.

Impairment of Hepcidin Upregulation by Lipopolysaccharide in the Interleukin-6 Knockout Mouse Brain.

To find out whether the Interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) signaling pathway is involved in the expression of hepcidin in the mouse brain in vivo, we investigated the phosphorylation of STAT3, as well as the expression of hepcidin mRNA, ferroportin 1 (Fpn1) and ferritin light chain (Ft-L) proteins in the cortex and hippocampus of LPS-treated wild type (IL-6+/+) and IL-6 knockout (IL-6-/-) mice. We demonstrated that IL-6 knockout could significantly reduce the response of hepcidin mRNA, phospho-STAT3, Fpn1 and Ft-L protein expression to LPS treatment, in both the cortex and hippocampus of mice. Also, Stattic, an inhibitor of STAT3, significantly reduced the expression of phospho-STAT3 and hepcidin mRNA in the cortex and hippocampus of the LPS-treated wild type mice. These findings provide in vivo evidence for the involvement of the IL-6/STAT3 signaling pathway in the expression of hepcidin.