Multifunctional Oxygen-Generating Nanoflowers for Enhanced Tumor Therapy.

Sonodynamic therapy (SDT) and chemotherapy have received great attention as effective methods for tumor treatment. However, the inherent hypoxia of the tumor greatly hinders its therapeutic efficacy. In this work, a tumor microenvironment-responsive biodegradable nanoplatform SiO2-MnO2-PEG-Ce6&DOX (designated as SMPC&D) is fabricated by encapsulating manganese oxide (MnO2) into silica nanoparticles and anchoring poly(ethylene glycol) (PEG) onto the surface for tumor hypoxia relief and delivery, then loaded with sonosensitizer Chlorin e6 (Ce6) and chemotherapeutic drug doxorubicin (DOX) for hypoxic tumor treatment. We evaluated the physicochemical properties of SMPC&D nanoparticles and the tumor therapeutic effects of chemotherapy and SDT under ultrasound stimulation in vitro and in vivo. After endocytosis by tumor cells, highly expressed glutathione (GSH) triggers biodegradation of the nanoplatform and MnO2 catalyzes hydrogen peroxide (H2O2) to generate oxygen (O2), thereby alleviating tumor hypoxia. Depleting GSH and self-supplying O2 effectively improve the SDT efficiency both in vitro and in vivo. Ultrasonic stimulation promoted the release and cellular uptake of chemotherapy drugs. In addition, the relieved hypoxia reduced the efflux of chemotherapy drugs by downregulating the expression of the P-gp protein, which jointly improved the effect of chemotherapy. This study demonstrates that the degradable SMPC&D as a therapeutic agent can achieve efficient chemotherapy and SDT synergistic therapy for hypoxic tumors.

Correlation between the Density of Acipenser sinensis and Its Environmental DNA.

Since the construction of the Gezhouba Dam, Chinese sturgeon (Acipenser sinensis) numbers have gradually declined, rendering this species critically endangered according to the International Union for the Conservation of Nature. Environmental DNA (eDNA) technology plays an important role in monitoring the abundance of aquatic organisms. Species density and biomass have been proven to be estimable by researchers, but the level of accuracy depends on the specific species and ecosystem. In this study, juvenile A. sinensis, an endangered fish, were selected as the research target. Under controlled laboratory conditions in an aquarium, one, two, four, six, and eight juvenile A. sinensis were cultured in five fish tanks, respectively. Water samples were filtered at eight different time points for eDNA content analysis. Additionally, eDNA yield was tested at six different time points after a 0.114 ind./L density of A. sinensis was removed, and the employed degradation model was screened using the Akaike information criterion (AIC) and the Bayesian information criterion (BIC). The results showed that eDNA content remained stable after 3 days and exhibited a significant positive linear correlation with the density of A. sinensis (R2 = 0.768~0.986). Furthermore, eDNA content was negatively correlated with the 3-day period after the removal of A. sinensis. The power function had the smallest AIC and BIC values, indicating better fitting performance. This study lays a momentous foundation for the application of eDNA for monitoring juvenile A. sinensis in the Yangtze Estuary and reveals the applicability of eDNA as a useful tool for assessing fish density/biomass in natural environments.

Optimization of the flow conditions in the spawning ground of the Chinese sturgeon (Acipenser sinensis) through Gezhouba Dam generating units.

Chinese sturgeon (Acipenser sinensis) is a critically endangered species, and waters downstream from Gezhouba Dam are the only known spawning ground. To optimize the velocity conditions in the spawning ground by controlling the opening mode of Gezhouba Dam generator units, a mathematical model of Chinese sturgeon spawning ground was established in FLOW-3D. The model was evaluated with velocity measurements, and the results were determined to be in good agreement. By inverting the 2016-2019 field monitoring results, the model shows that the preferred velocity range for Chinese sturgeon spawning is 0.6-1.5 m/s. Velocity fields of different opening modes of the generator units were simulated with identical discharge. The suitable-velocity area was maximal when all units of Dajiang Plant of Gezhouba Dam were open. For discharges below 12,000 m3/s, most of the area was suitable; for discharges above 12,000 m3/s, the suitable area rapidly decreased with increasing discharge. A comparison of suitable areas under high-flow showed that at discharges of 12,000-15,000 m3/s, opening 11-13 units on the left side was optimal. For discharges above 15,000 m3/s, all units should be open. We used these results to recommend a new operation scheme to support the conservation of Chinese sturgeon.

Control of angiogenesis by inhibitor of phospholipase A2.

OBJECTIVE: To investigate the potential effects of angiogenic process by secretory phospholipase A2 (sPLA2) inhibitor-HyPE (linking N-derivatized phosphatidyl-ethanolamine to hyaluronic acid) on human bone marrow endothelial cell line (HBME-1). METHODS: In order to examine the suppressing effects of HyPE on HBME-1 proliferation, migration, and capillary-like tube formation, HBME-1 were activated hy angiogenic factor, specifically by basic fibroblast growth factor (b-FGF), vascular endothelial growth factor (VEGF), and oncostatin M (OSM) (at a final concentration of 25, 20, and 2.5 ng/mL, respectively), then HBME-1 proliferation, migration, and tube formation were studied in the absence or presence of HyPE. HBME-1 tube formation was specially analyzed in fibrin gel. RESULTS: HyPE effectively inhibited HBME-1 proliferation and migration as a dose-dependent manner, whatever HBME-1 were grown in the control culture medium or stimulated with b-FGF, VEGF, or OSM. In fibrin, the formations of HBME-1 derived tube-like structures were enhanced by all angiogenic factors, but these were strongly suppressed by HyPE. CONCLUSIONS: The results support the involvement of sPLA2 in angiogenesis. It is proposed that sPLA2 inhibitor introduces a novel approach in the control of cancer development.

[Thalidomide inhibits the angiogenic activity of culture supernatants of multiple myeloma cell line].

OBJECTIVE: To investigate the pro-angiogenic effects of several multiple myeloma (MM) cell line culture supernatants on human bone marrow endothelial cell (HBMEC) proliferation, migration, and capillary formation, and the anti-angiogenic effects of thalidomide. METHODS: HBMEC was cultured in the presence of MM cell lines (IM9, XG1, U266 and MOLP-5) supernatants. Proliferation and migration of HBMEC were determined, capillary-like tubule formation of HBMEC was examined in fibrin and Matrigel. The inhibiting effect of thalidomide was investigated by adding it into myeloma cell line culture supernatants. Vascular endothelial growth factor (VEGF) was measured by ELISA. RESULTS: (1) MM cell lines culture supernatants promoted HBMEC proliferation and migration. (2) In fibrin and Matrigel, capillary-like tubule network formation promoted by the supernatants. (3) All of these effects could be inhibited by thalidomide. (4) This effect was not related to VEGF in the supernatants. CONCLUSIONS: MM cell line promote proliferation, migration and tubule formation by secreting VEGF or other several cytokines. Thalidomide can inhibit these effects.

Methylation of p16 and p15 genes in multiple myeloma.

OBJECTIVE: To investigate the frequency of p16 and p15 gene methylation in multiple myeloma (MM), and its relationship with bone marrow cell apoptosis and clinical outcome. METHODS: Twenty-two patients with MM were studied to detect p16 and p15 gene methylation. Methylation-specific polymerase chain reaction (MSP) was used to detect gene methylation, and terminal transferase-mediated dUTP nick end-labeling (TUNEL) was used to detect cell apoptosis. RESULTS: p16 and/or p15 gene methylatoin was detected in 10 of 22 patients (45.4%). There were 3 patients with p16 gene methylation, 9 patients with p15 gene methylation, and 2 patients with both genes methylation. The incidence of methylation of p15 gene was higher than that of p16 gene (P < 0.05). The patients with p16 and/or p15 gene methylation had a delayed cell apoptosis, poor response to chemotherapy, and a short over-all survival (OS). CONCLUSION: The methylation of p16 and/or p15 gene plays a key role in MM apoptosis pathogenesis. The patients with both p16 and p15 gene methylation had a poor prognosis.

[Study on angiogenesis of multiple myeloma in vitro].

Angiogenesis is a necessary step in tumor progression, and it correlates an unfavorable prognosis. In multiple myeloma, bone marrow microvessel density and angiogenesis grading correlated with plasma cell labeling index and are poor survival predictors, but the study of myeloma's angiogenesis is very rare. This article was to study the effect of multiple myeloma cell line conditioned media on the proliferation, migration and angiogenesis of human bone marrow endothelial cells (HBMEC). The multiple myeloma cell line conditioned media were obtained by using RPMI 1640 media containing 2% fetal bovine serum (FBS) to cultivate myeloma cell lines for 18 hours. Proliferation and migration of HBMEC were detected by using those media to cultivate HBMEC. Capillary tube formation was performed by using microcarriers cytodex-3 covered with HBMEC in three-dimensional fibrin matrices. The results showed that myeloma conditioned media induced HBMEC's proliferation and migration (P < 0.001), and those media induced capillary tube formation (length and width) of HBMEC (P < 0.001). It was concluded that myeloma cell lines induce HBMEC's proliferation, migration, and capillary tube formation by secreting several cytokines.