Targeted fluorescent imaging of a novel FITC-labeled PSMA ligand in prostate cancer

In this study, we synthesized a novel fluorescein isothiocyanate (FITC)-labeled prostate-specific membrane antigen (PSMA) ligand (PSMA-FITC) via the Fmoc solid-phase synthesis method, and the application value of PSMA-FITC in targeted fluorescence imaging of PSMA-positive prostate cancer was evaluated. The PSMA ligand developed based on the Glu-urea-Lys structure was linked to FITC by aminocaproic acid (Ahx) to obtain PSMA-FITC. The new probe was evaluated in vitro and in vivo. Fluorescence microscopy examination of PSMA-FITC in PSMA(+) LNCaP cells, PSMA(−) PC3 cells, and blocked LNCaP cells showed that the binding of PSMA-FITC with PSMA was target-specific. For in vivo optical imaging, PSMA-FITC exhibited rapid 22Rv1 tumor targeting within 30 min of injection, and the highest tumor-background ratio (TBR) was observed 60 min after injection. The TBR was 3.45 ± 0.31 in the nonblocking group and 0.44 ± 0.13 in the blocking group, which was consistent with the in vitro results. PSMA-FITC is a promising probe and has important reference value for the development of PSMA fluorescent probes. In the future, it can be applied to obtain accurate tumor images for radical prostatectomy.

Practical and Regioselective Synthesis of C4-Alkylated Pyridines

The direct position-selective C–4 alkylation of pyridines has been a longstanding challenge in heterocyclic chemistry, particularly from pyridine itself. Historically this has been addressed using pre-functionalized materials to avoid overalkylation and mixtures of regioisomers. This study reports the invention of a simple maleate-derived blocking group for pyridines that enables exquisite control for Minisci-type decarboxylative alkylation at C–4 that allows for inexpensive access to these valuable building blocks. The method is employed on a variety of different pyridines and carboxylic acid alkyl donors, is operationally simple, scalable, and is applied to access known structures in a rapid and inexpensive fashion. Finally, this work points to an interesting strategic departure for the use of Minisci chemistry at the earliest possible stage (native pyridine) rather than current dogma that almost exclusively employs Minisci as a late-stage functionalization technique.

Practical and Regioselective Synthesis of C4-Alkylated Pyridines

The direct position-selective C–4 alkylation of pyridines has been a longstanding challenge in heterocyclic chemistry, particularly from pyridine itself. Historically this has been addressed using pre-functionalized materials to avoid overalkylation and mixtures of regioisomers. This study reports the invention of a simple maleate-derived blocking group for pyridines that enables exquisite control for Minisci-type decarboxylative alkylation at C–4 that allows for inexpensive access to these valuable building blocks. The method is employed on a variety of different pyridines and carboxylic acid alkyl donors, is operationally simple, scalable, and is applied to access known structures in a rapid and inexpensive fashion. Finally, this work points to an interesting strategic departure for the use of Minisci chemistry at the earliest possible stage (native pyridine) rather than current dogma that almost exclusively employs Minisci as a late-stage functionalization technique.

Practical and Regioselective Synthesis of C4-Alkylated Pyridines

The direct position-selective C–4 alkylation of pyridines has been a longstanding challenge in heterocyclic chemistry, particularly from pyridine itself. Historically this has been addressed using pre-functionalized materials to avoid overalkylation and mixtures of regioisomers. This study reports the invention of a simple maleate-derived blocking group for pyridines that enables exquisite control for Minisci-type decarboxylative alkylation at C–4 that allows for inexpensive access to these valuable building blocks. The method is employed on a variety of different pyridines and carboxylic acid alkyl donors, is operationally simple, scalable, and is applied to access known structures in a rapid and inexpensive fashion. Finally, this work points to an interesting strategic departure for the use of Minisci chemistry at the earliest possible stage (native pyridine) rather than current dogma that almost exclusively employs Minisci as a late-stage functionalization technique.

Radiosynthesis of A Novel Antisense Imaging Probe Targeting LncRNA HOTAIR in Malignant Glioma

Background: Long non-coding RNA (lncRNA) HOTAIR was manifested amplifying in many human carcinomas, which could serve as a useful target for cancer therapy. The 99mTc radiolabeled antisense oligonucleotides (ASON) could visualize the expression of HOTAIR and provide a diagnostic value for malignant tumors. The aim of this study was to radiosynthesis 99mTc with HOTAIR ASON and investigate the in vivo imaging in malignant glioma xenografts.Methods: The ASON targeting lncRNA HOTAIR as well as mismatched ASON probe (ASONM) were designed and modified. The radiolabeling of 99mTc with two probes were via the conjugation of bifunctional chelator HYNIC. Then probes were purified by Sephadex G25 and tested for their radiolabeling efficiency and purity, as well as stability by ITLC and gel electrophoresis. Then the radiolabeled probes were transfected with lipofectamine 2000 for cellular uptake test and the next experimental use. Furthermore, biodistribution study and SPECT imaging were performed at different times after probes were intravenously injected in glioma tumor-bearing mice models. All data were analyzed by statistical software.Results: The labeling efficiencies of 99mTc-HYNIC-ASON and 99mTc-HYNIC-ASONM measured by ITLC were (91 ±1.5) % and (90 ±0.6) %, respectively, and the radiochemical purity were more than 89%. The probes showed good stability within 12 hours. Gel electrophoresis confirmed that the oligomers were successfully radiolabeled no significant degradation was found. Cellular uptake experiment showed that liposomes had the ability to carry probes into cells. Biodistribution study demonstrated that liposome coated 99mTc-HYNIC-ASON had significantly higher uptake in the tumor and higher T/M ratio than the mismatched group. Meanwhile, the tumor was clearly shown at 1-hour post probe injection of liposome coated 99mTc-HYNIC-ASON on SPECT/CT imaging, no tumor was seen in mismatched and blocking group.Conclusion: The liposome encapsulated 99mTc-HYNIC-ASON probe can be used in the in vivo, real-time imaging of lncRNA HOTAIR expression in malignant glioma.

Radiosynthesis of A Novel Antisense Imaging Probe Targeting LncRNA HOTAIR in Malignant Glioma.

Background: Long non-coding RNA (lncRNA) HOTAIR was manifested overexpressing and amplifying in many human carcinomas, which could serve as a useful target for cancer therapy. The 99mTc radiolabeled antisense oligonucleotides (ASON) could visualize the expression of HOTAIR and provide a diagnostic and therapeutic value for malignant tumors. The aim of this study was to radiosynthesis 99mTc with HOTAIR ASON and investigate the in vivo imaging in malignant glioma xenografts. Methods: The ASON targeting lncRNA HOTAIR as well as mismatched ASON probe (ASONM) were designed and modified. The radiolabeling of 99mTc with two probes was via the conjugation of bifunctional chelator HYNIC. Then the probes were purified by Sephadex G25 and tested for its radiolabeling efficiency and purity, as well as stability by iTLC and gel electrophoresis. Then the radiolabeled probes were transfected with lipofectamine 2000 for cellular uptake test and the next experimental use. Furthermore, biodistribution study and SPECT imaging was performed at different time after probes were intravenously injected in U87 tumor bearing nude mice models. All data were analyzed by statistical software. Results: The labeling efficiencies of 99mTc-HYNIC-ASON and 99mTc-HYNIC-ASONM measured by iTLC were (91 ±1.5) % and (90 ±0.6) %, respectively, and the radiochemical purity were more than 89%. The probes showed good stability within 12 hours for high radiochemical purity. Gel electrophoresis confirmed that the oligomers were successfully radiolabeled no significant degradation were found. Cellular uptake experiment showed that liposomes had ability to carry probes into cells. Biodistribution study demonstrated that liposome coated 99mTc-HYNIC-ASON had significantly higher uptake in the tumor and higher tumor to muscle ratio than mismatched group. Meanwhile tumor was clearly shown at 1 hours post probe injection of Liposome coated 99mTc-HYNIC-ASON on SPECT/CT imaging, compared with mismatched and blocking group. Conclusion: The Liposome encapsulated 99mTc-HYNIC-ASON probe can be radiosynthesized and used in the in vivo, real-time imaging of lncRNA HOTAIR expression in malignant glioma.

Study on the Effect of Composite Nanoparticles on Corneal Epithelial Cell Immune Mechanism Based on Dectin-1 Signaling Pathway

In order to investigate the role of composite nanoparticles in the immune stage, we observed the expression of R-1 in anti-mycotic infection of human corneal epithelial cells, and divided the experiment into control group, fungal stimulation group, Gw507 blocking group and Dectin-1. In the inhibitor group, the immune effect of human corneal epithelial cells was studied. Subsequently, the expression of total R-1 and phosphorylated form of p-R-1 in each experimental group was detected by western blot method. Finally, real-time quantitative PCR was used to detect the expression of factors IL-6 and IL-8. We concluded that p-R-1 was slightly expressed in the control group. After 15 minutes of fungal stimulation, the expression level in the experimental group was significantly higher than that in the blank group, and the difference was statistically significant (p < 0.05). In the blocking group of two different inhibitors, the expression of p-R-1 was lower than that in the fungal stimulation experimental group, and the difference was statistically significant (p < 0.05). Therefore, R-1 is expressed in corneal epithelial cells and the fungus exerts its antifungal effect through the Dectin-1 signaling pathway.

Effect of preoperative carbohydrate intake on inflammatory factors and clinical outcomes in elderly patients undergoing radical prostatectomy: a single-center, double-blind randomized controlled trial

BACKGROUND To investigate the advantages of Carbohydrate (CHO) in inflammatory factors, comfort and clinical outcomes in elderly patients with open radical prostatectomy. METHODS Patients of ≥ 65 years old with radical prostatectomy who underwent open radical prostatectomy were randomized to the CHO group, placebo group, and conventional water-blocking group. Patients in the CHO group and placebo group received oral CHO, 800 ml of placebo water before surgery,and oral CHO and placebo water 400 ml 2 to 3 hours before surgery; the water-free group did not drink any liquid. The main test indicators are inflammatory factors, comfort and clinical outcomes. RESULTS 28 patients in the CHO group, 30 in the placebo group, and 32 in the conventional water-blocking group were included in the study. The three groups matched well in age, body mass index, the grade of (American Society of Anesthesiologists)ASA, operation time, blood loss, and fluid volume.CHO reduces IL-6 of Day1 and Day7 (P = 0.009, 0.005, respectively), IL-8 (P = 0.005) of Day1, Day1, Day 3, and Day 7 TNF (P = 0.001, 0.006, 0.003 respectively) compared with the water-stopping group ; placebo water reduced Day 1 and Day 7 TNF (P = 0.005, 0.038, respectively), Day 1of IL-8 (P = 0.045). CHO reduced Day3 of TNF (P = 0.026) compared to placebo. In the CHO group and the placebo group, the morning thirst scores (0.68, 1.26, respectively) and starvation (0.24, 0.47, respectively)were decreased. The first time to leave bed in the conventional water-blocking group (39.21 (15–93) h) was much later than in the CHO group (28.57 (10–100) h) and the placebo group (28.71 (12–70) h). Conclusion Compared with routine water ban, preoperative CHO and placebo water can reduce the levels of IL-6, IL-8 and TNF in elderly patients undergoing radical prostatectomy, which can improve the patient's preoperative comfort and shorten the patient's first time to leave bed. Compared with placebo water, CHO has no significant advantage in improving inflammatory factors and clinical outcomes.

Diagnostic Value of CT Value of Arterial Angiography in Femoral Artery Obstructive Disease

Objective: To compare the changes of CT values of distal femoral artery and radial artery obstructive lesions and whether CTA showed the diagnosis of complete occlusion of lower extremity arteries by CT angiography and DSA. Materials and Methods: A total of 50 consecutive patients with femoral artery and radial artery occlusion were enrolled and retrospectively studied, aged 32–83 years, mean 68.5 ± 8.7 years old; 35 males and 15 females, reverse descending The sign was defined as the contrast fill gradient in the distal lumen of the vascular occlusion site, which was characterized by a progressive increase in the CT value of the distal lumen of the obstructed lesion from proximal to distal. DSA was used as the criterion to statistically analyze the incidence of CT angiographic inverse descending signs and collateral circulation in chronic complete obstructive lesions and partial obstructive lesions of the femoral artery and radial artery, and statistical analysis was performed. Results: The rates of reversed CT values in the chronic total occlusion group and the partial occlusion group were 76.9% (20/26) and 20.8% (5/24), respectively. The signs of reverse degeneration were significantly more common in the chronic complete occlusion group (X2 = 13.1). P < 0.05). The incidence of peripheral collateral circulation in the chronic occlusion group and partial obstruction group was 80.8% (21/26) and 29.2% (7/24), respectively. The incidence of collateral circulation in the chronic complete occlusion group was significantly higher than that in the partial occlusion group. Blocking group (X2 = 13.5, P < 0.05). The sensitivity of CT and angiographic collateral signs for the diagnosis of chronic complete occlusion of the femoral artery and radial artery was 92.3%, and the specificity was 70.8%. Conclusions: The inverse degeneration of CT values and the signs of CTA collateral circulation have a high specificity for the diagnosis of chronic complete occlusion of the femoral artery and radial artery, and help to identify partial occlusion of the femoral artery and radial artery and chronic complete occlusion.