Enhancing Targeted Therapy in Hepatocellular Carcinoma through a pH-Responsive Delivery System: Folic Acid-Modified Polydopamine-Paclitaxel-Loaded Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Nanoparticles.

Currently, there is an inherent contradiction between the multifunctionality and excellent biocompatibility of anticancer drug nanocarriers, which limits their application. Therefore, to overcome this limitation, we aimed to develop a biocompatible drug delivery system for the treatment of hepatocellular carcinoma (HCC). In this study, we employed poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) as the fundamental framework of the nanocarrier and utilized the emulsion solvent evaporation method to fabricate nanoparticles loaded with paclitaxel (PTX), known as PTX-PHBV NPs. To enhance the tumor-targeting capability, a dopamine self-polymerization strategy was employed to form a pH-sensitive coating on the surface of the nanoparticles. Then, folic acid (FA)-targeting HCC was conjugated to the nanoparticles with a polydopamine (PDA) coating by using the Michael addition reaction, resulting in the formation of HCC-targeted nanoparticles (PTX-PHBV@PDA-FA NPs). The PTX-PHBV@PDA-FA NPs were characterized and analyzed by using dynamic light scattering, scanning electron microscopy, fourier-transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis. Encouragingly, PTX-PHBV@PDA-FA NPs exhibited remarkable anticancer efficacy in an HCC xenograft mouse model. Furthermore, compared to raw PTX, PTX-PHBV@PDA-FA NPs showed less toxicity in vivo. In conclusion, these results demonstrate the potential of PTX-PHBV@PDA-FA NPs for HCC treatment and biocompatibility.

[Influence of different filling method-related sperm counting chambers and structural factors of disposable chambers on sperm motility].

Objective: To evaluate the effects of different filling method-related sperm counting chambers and the structural factors of Leja counting chambers on sperm motility using computer-assisted sperm analysis (CASA). METHODS: Using drop-filled Makler, capillary-loaded Leja and structurally modified Leja sperm counting chambers, we measured sperm concentration, the percentages of progressively motile sperm (PMS) and non-progressively motile sperm (NPMS), total sperm motility, curvilinear velocity (VCL), average path velocity (VAP), straight line velocity (VSL), beat-cross frequency (BCF), linearity (LIN), wobble (WOB) and straightness (STR) in the semen samples of 76 males by CASA and compared them between different chambers. RESULTS: The drop-filled Makler sperm counting chamber achieved remarkably higher PMS, NPMS, total sperm motility, VCL and VAP than the Leja chambers (P < 0.05). There were no statistically significant differences in VSL, BCF, LIN, WOB and STR between the Makler and Leja chambers (P > 0.05), or in sperm concentration, PMS, NPMS and total sperm motility between the capillary-loaded and structurally modified Leja counting chambers (P > 0.05). The ground edge and thickness of the coverslip of the Leja counting chamber produced no significant inference on the kinetic sperm parameters (P > 0.05). CONCLUSIONS: The drop-filled sperm counting chamber achieves significantly higher sperm motility and kinetic parameters than the capillary-loaded Leja chamber. The structural factors such as the ground edge and thickness of the coverslip of the Leja counting chamber do not influence the analysis of sperm parameters.

[Location of semen collection and semen quality: clinic-collected versus home-collected samples].

OBJECTIVE: To investigate the differences in semen quality between samples collected by masturbation in the clinic and at home. METHODS: Based on the WHO guidelines, we analyzed the ejaculates collected by masturbation in the clinic and at home from 342 men under infertility assessment and measured the contents of such biochemical markers in the seminal plasma as neutral α-glucosidase, zinc, and fructose. According to the location of semen collection, we divided the samples into two groups, clinic-collected and home-collected, and analyzed the differences in the semen parameters between the two groups with the SPSS 16.0 software. RESULTS: Compared with the clinic-collected semen, the home-collected samples had significantly higher mean values in semen volume (4.0 vs 4.9%), sperm concentration (41 vs 64 x 10(6)/ml), total sperm count (175 vs 270 x 10(6) per ejaculate), progressive sperm motility (40 vs 52%), total count of progressively motile sperm (82 vs 135 x 10(6) per ejaculate) (all P <0.05). No significant differences were found between the two groups in normal sperm morphology (4.0 vs 5.0%) and the contents of neutral α-glucosidase (26 vs 24 mU per ejaculate), zinc (8.0 vs 8.0 µmol per ejaculate), and fructose (62 vs 60 µmol per ejaculate) (all P >0.05). Abnormal sperm concentration (<20 x 10(6)/ml) was observed in significantly fewer of the home-collected samples than the clinic-collected ones (18% [62/342] vs 30% [103/342], P<0.05), and so was abnormal progressive sperm motility (<32%) (64% [219/342] vs 75% [256/342], P<0.05). CONCLUSION: Our findings show that semen samples collected by masturbation at home has a higher quality than those collected in the clinic. So the location of semen collection should be taken into consideration in infertility investigation.

Enrichment of the flavonoid fraction from Eucommia ulmoides leaves by a liquid antisolvent precipitation method and evaluation of antioxidant activities in vitro and in vivo.

Eucommia ulmoides leaves originate from the dry leaves of the Eucommia ulmoides plant. Flavonoids are the main functional components of Eucommia ulmoides leaves. Some flavonoids such as rutin, kaempferol and quercetin are rich in Eucommia ulmoides, and they have outstanding antioxidant efficacy. However, the poor water solubility significantly affects the bioavailability of flavonoids. In this study, we used a liquid antisolvent precipitation (LAP) method to enrich the main flavonoid fractions in Eucommia ulmoides leaves, and prepared nanoparticles by the LAP method to increase flavonoids' solubility and antioxidant properties. The technological parameters were optimized by Box-Behnken Design (BBD) software and were displayed as follows: (1) total flavonoids (TFs) concentration: 83 mg mL-1; (2) antisolvent-solvent ratio: 11; (3) deposition temperature: 27 °C. Under optimal processing conditions, the purity and recovery rate of TFs were 88.32% ± 2.54% and 88.08% ± 2.13%, respectively. In vitro experiments showed that the radical scavenging IC50 values for DPPH, ABTS, hydroxyl radicals and superoxide anions were 16.72 ± 1.07, 10.76 ± 0.13, 227.68 ± 18.23 and 335.86 ± 15.98 µg mL-1, respectively. In vivo studies showed that the obtained purified flavonoid (PF) (100, 200, 400 mg kg-1) treatment is able to improve CCl4-induced liver and kidney damage through adjusting, superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) levels. These results demonstrated that the LAP method is capable of extracting TFs from Eucommia ulmoides leaves with high bioaccessibility.

[Effects of a microfluidic sperm sorter on sperm routine parameters and DNA integrity].

OBJECTIVE: To investigate the effects of a microfluidic sperm sorter on the routine parameters and DNA integrity of human sperm. METHODS: We divided 40 semen samples into two aliquots and performed sperm sorting using a self-made polydimethylsiloxane microfluidic sperm sorter and the swim-up method, respectively. Then we evaluated and compared the effects of these two methods on the sperm routine parameters and DNA integrity by computer-assisted sperm analysis and sperm chromatin dispersion test. RESULTS: After processing, sperm motility, normal morphology and tail hypoosmotic swelling rate were significantly improved, while sperm DNA damage remarkably decreased (P < 0.01). The microfluidic sperm sorter achieved a significantly lower rate of sperm DNA damage than the swim-up method ([ 8.4 +/- 5.8 ]% vs [16.4 +/- 9.2] %, P < 0.01), but no statistically significant differences were found in all other parameters between the two methods. CONCLUSION: High-quality sperm with less DNA integrity damage could be obtained in sperm sorting with the microfluidic sperm sorter.