Capsella bursa-pastoris (L.) Medic. extract alleviate cataract development by regulating the mitochondrial apoptotic pathway of the lens epithelial cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Capsella bursa-pastoris (L.) Medic. (CBP) is a cruciferous plant valuable in reducing fever, improving eyesight and calming the liver. This herb was recorded in the Compendium of Materia Medica for cataract treatment. AIM OF THE STUDY: To determine the effects and mechanism of CBP on cataract prevention and treatment using a selenite cataract model. MATERIALS AND METHODS: The main compounds in CBP extract were analyzed by UPLC, 1H-NMR and 13C-NMR spectroscopic techniques. Flavonoids formed a significant proportion of its compounds, thus necessitating an evaluation of their inhibitory effects on the development of cataract using a selenite cataract model. The protective effects of CBP flavonoids (CBPF) against oxidative damage and the modulation of mitochondrial apoptotic pathway were subsequently verified on H2O2-treated SRA01/04 lens epithelial cells. RESULTS: CBPF significantly alleviated the development of cataract by decreasing the MDA level and increasing the GSH-Px and SOD levels in the lens. It also inhibited H2O2-induced apoptosis in SRA01/04 cells, increased the expression of Bcl-2 protein and decreased the expressions of Caspase-3 and Bax proteins. CONCLUSION: CBPF exerts a significant preventive effect on cataract development by regulating the mitochondrial apoptotic pathway of the lens epithelial cells. It is thus a potent traditional Chinese medicine (TCM) whose application should be further developed for the clinical treatment of cataract.

[Research progress on rutin derivatives].

Compounds derived from natural products present satisfactory efficacy in disease prevention and treatment. The use of chemical substances in plants to promote healthhas increasingly attracted people's attention. Rutin, a typical flavonoid, is mainly found in various vegetables, fruits and Chinese herbal medicines. As a natural antioxidant, it features many pharmacological activities, such as anti-inflammation, anti-virus, anti-tumor, and prevention and treatment of cardiovascular and cerebrovascular diseases. However, the low bioavailability and poor water solubility limit its clinical application. In view of this, its structure is optimized and modified to afford rutin derivatives with good solubility, high bioavailability, stable metabolism and small toxic side effects. So far, a large number of rutin ethers, esters, and complexes have been synthesized and undergone activity testing. This paper reviews the structural modification of rutin in recent years, and the obtained derivatives have excellent properties and significant biological activity.

Study on volume change and scanning electron microscopy observation of silica-filled solution polymerized styrene-butadiene rubber/cis-1,4-polybutadiene rubber blends upon stretching.

Solution polymerized styrene-butadiene rubber/cis-1,4-polybutadiene rubber (SBR/BR) blends filled with silica is widely used system in tread compounds for passenger tires. The application of silane coupling agents greatly improves the interaction between polymer and filler through chemical bonds. By testing a series of SBR/BR blends filled with different specific surface area and content of silica, we measured the volume change data of the compounds upon stretching and plotted the corresponding ΔV/V-ε curves. In order to normalize for stress differences, ΔV/(Vσ)-ε curves were also plotted using stress-strain data. Scanning electron microscopy (SEM) was used to observe the microstructures in the vulcanizate in situ when stretched. The dispersion, agglomeration, and vacuole formation process can be visualized clearly in the SEM images.

The therapeutic efficacy of 177Lu-DOTATATE/DOTATOC in advanced neuroendocrine tumors: A meta-analysis.

BACKGROUND: Somatostatin analog therapies showed great potential for patients suffering advanced neuroendocrine tumors (NETs). This study was aimed to evaluate the therapeutic efficacy of Lu-DOTATATE/DOTATOC (Lu-octreotate/octreotide) peptide receptor radionuclide therapy (PRRT) in advanced or inoperable NETs patients. METHODS: Pubmed, Web of Science, Embase and Cochrane Library were searched from 1950 to April 2019. Eligible studies should include randomized or nonrandomized controlled trials (RCTs)-based investigations of Lu-octreotate/octreotide PRRT for NETs. All these studies were assessed with Response Evaluation Criteria in Solid Tumors (RECIST), RECIST 1.1, Southwest Oncology Group (SWOG) criteria or World Health Organization (WHO) criteria. Disease response rates (DRRs) and disease control rates (DCRs) were calculated according to each response criteria group. DRRs were defined as the percentages of patients with complete response (CR) + partial response (PR), while DCRs represented the percentages of patients with CR+ PR+ stable disease (SD). The pooled proportions were calculated with either a fixed-effects model or a random-effects model depending on the test for heterogeneity. RESULTS: A total of 22 studies (1758 patients) were included in this meta-analysis: 8 studies with 478 patients met RECIST criteria, 10 studies with 1127 patients met RECIST 1.1 criteria, 5 studies with 459 patients met SWOG criteria, and 1 study with 40 patients met WHO criteria, and among these articles 1 study met both RECIST and RECIST 1.1 criteria and 1 met both RECIST 1.1 and SWOG criteria. The pooled DRRs were 33.0% (95% CI: 25.0%-42.0%, I = 65%), 35.0% (95% CI: 26.0%-45.0%, I = 91%) and 25.0% (95% CI: 14.0%-36.0%, I = 84%) according to RECIST, RECIST 1.1 and SWOG criteria, respectively. The pooled DCRs were 79.0% (95% CI: 75.0%-83.0%, I = 97%), 83.0% (95% CI: 78.0%-88.0%, I = 0) and 82.0% (95% CI: 75.0%-89.0%, I = 91%), respectively. CONCLUSION: In advanced NETs patients, DRRs and DCRs were significantly elevated after initial treatment with Lu-DOTATATE PRRT, which shows that this treatment would be beneficial and promising for advanced or inoperable NETs patients.

Systematically characterize the substance basis of Jinzhen oral liquid and their pharmacological mechanism using UPLC-Q-TOF/MS combined with network pharmacology analysis.

Jinzhen oral liquid (JZ) is a classical traditional Chinese medicine formula used for the treatment of children lung disease. However, the effective substance of JZ is still unclear. In this study, we used lung injury rat model to study the protective effect of JZ, through UPLC-Q-TOF/MS detection coupled with metabolic research and network pharmacology analysis. Fortunately, 31 absorbed prototype constituents and 41 metabolites were identified or tentatively characterized based on UPLC-Q-TOF/MS analysis, and the possible metabolic pathways were hydroxylation, sulfation and glucuronidation. We optimized the data screening in the early stage of network pharmacology by collecting targets based on adsorbed constituents, and further analyzed the main biological processes and pathways. 24 selected core targets were frequently involved in reactive oxygen species metabolic process, dopaminergic synapse pathway and so on, which might play important roles in the mechanisms of JZ for the treatment of lung injury. Overall, the absorbed constituents and their possible metabolic pathways, as well as the absorbed constituent-target-disease network provided insights into the mechanisms of JZ for the treatment of lung injury. Further studies are needed to validate the biological processes and effect pathways of JZ.

Anti-apoptosis effects of vascular endothelial cadherin in experimental corneal neovascularization.

AIM: To explore the effects and mechanism of vascular endothelial cadherin (VE-cadherin) on experimental corneal neovascularization (CRNV). METHODS: Mouse corneas were burned with sodium hydroxide to build a CRNV model. The burned corneas were locally administrated with anti-mouse VE-cadherin neutralizing antibody. Annexin V and cluster of differentiation 31 (CD31) double staining was used to measure vascular endothelial cell apoptosis with the use of flow cytometry (FCM). The protein expression of NADPH oxidase 2 (Nox2), caspase-3, and protein kinase C (PKC) in the burned corneas were examined by Western blot. Human retinal endothelial cell (HREC) proliferation was detected using a Cell Counting Kit 8 (CCK-8) assay in vitro. RESULTS: The amount of CRNV peaked two weeks after the alkali burn. FCM confirmed that VE-cadherin neutralizing antibody treatment increased CD31 positive cell apoptosis. Western blot revealed that the intracorneal protein expression of Nox2 and caspase-3 were up-regulated, while PKC was down-regulated in the VE-cadherin neutralizing antibody administrated group. CCK-8 assay showed that VE-cadherin neutralizing antibody markedly inhibited HREC proliferation. CONCLUSION: VE-cadherin exhibited an anti-apoptosis effect through enhanced PKC signaling and an enhanced cell proliferation pathway.

Cadmium sensitivity, uptake, subcellular distribution and thiol induction in a marine diatom: exposure to cadmium.

The aims of this study were to (1) evaluate the changes in the Cd tolerance of a marine diatom after exposure under different Cd concentrations for various durations and (2) to explore the potential subcellular and biochemical mechanisms underlying these changes. The 72-h toxicity, short-term Cd uptake, subcellular Cd distribution, as well as the synthesis of phytochelatins (PCs) were measured in a marine diatom Thalassiosira nordenskioeldii after exposure to a range of free Cd ion concentrations ([Cd(2+)], 0.01-84nM) for 1-15 days. Surprisingly, the diatoms did not acquire higher resistance to Cd after exposure; instead their sensitivity to Cd increased with a higher exposed [Cd(2+)] and a longer exposure period. The underlying mechanisms could be traced to the responses of Cd cellular accumulation and the intrinsic detoxification ability of the preconditioned diatoms. Generally, exposure to a higher [Cd(2+)] and for a longer period increased the Cd uptake rate, cellular accumulation, as well as the Cd concentration in metal-sensitive fraction (MSF) in these diatoms. In contrast, although PCs were induced by the environmental Cd stress (with PC(2) being the most affected), the increased intracellular Cd to PC-SH ratio implied that the PCs' detoxification ability had reduced after Cd exposure. All these responses resulted in an elevated Cd sensitivity as exposed [Cd(2+)] and duration increased. This study shows that the physiological/biochemical and kinetic responses of phytoplankton upon metal exposure deserve further investigation.

Cadmium sensitivity, uptake, subcellular distribution and thiol induction in a marine diatom: Recovery from cadmium exposure.

Studies in the recovery from metal stress and the tolerance development to metal exposure of aquatic organisms are important for the understanding of epidemic pollution. In this study, the responses of a marine diatom, Thalassiosira nordenskioeldii, following recovery from environmental cadmium (Cd) stress were investigated. The diatoms were exposed to different concentrations of Cd for 7 days, and were then allowed different periods of time to recover. The Cd sensitivity increased after recovery from Cd stress, followed by a gradual restoration. The extent of restoration depended on both the recovery time and the environmental Cd stress during the exposure period. A complete restoration of Cd tolerance proved to be impossible for cells pre-exposed to High-Cd. The Cd cellular burden and subcellular Cd concentration decreased to the control level within the first day of recovery, indicating that the elevated sensitivity may have been due to the accumulation of functional damage caused by Cd exposure instead of a result of physical Cd accumulation. The rapid change in phytochelatins (PC) to both the increase in and the withdrawal of environmental Cd stress made it a good quantitative bioindicator of environmental Cd contamination. However, the relationships between Cd distribution in the metal sensitive fraction (MSF-Cd) or intracellular Cd to thiol ratio (intra-Cd/PC-SH) and the relative change in the median inhibition [Cd(2+)] ([Cd(2+)]-based-IC(50), i.e., Cd sensitivity) differed for the various exposure and recovery periods tested. Our study suggests that more attention should be given to the recovery of aquatic organisms from episodic metal exposure.

Cadmium in three marine phytoplankton: accumulation, subcellular fate and thiol induction.

We explored the possible mechanisms leading to differential Cd sensitivity in three marine phytoplankton (the diatom Thalassiosira pseudonana, the dinoflagellate Prorocentrum minimum and the green alga Chlorella autotrophica) based on their Cd accumulation, Cd subcellular distribution, and phytochelatin (PC) synthesis. The most sensitive species, T. pseudonana, generally exhibited the highest Cd body burden and organelle (org)-Cd concentration. C. autotrophica, the most tolerant species to Cd, had the smallest org-Cd accumulation, as well as a much higher percentage of cellular debris-Cd, which may play an important role in Cd detoxification. The dinoflagellate P. minimum, with a sensitivity between the diatoms and green algae, had a comparable Cd body burden but higher percentage of org-Cd than C. autotrophica. Although the induction of PCs was dependent on the species, the intracellular (intra)-Cd/PC-SH ratio showed a strong linear log-log relationship with [Cd(2+)], suggesting that this ratio could possibly be a biomarker for environmental [Cd(2+)] stress. With the increases of the intra-Cd/PC-SH ratio, these three species of phytoplankton exhibited clearly different patterns of growth inhibition, implying that the effectiveness of PCs as a detoxification pathway is dependent on the species. The lowest intra-Cd/PC-SH toxicity threshold for T. pseudonana implied its low PC-Cd capacity. Furthermore, the sudden slowdown of growth inhibition when the intra-Cd/PC-SH ratio reached 33 implied the launch of other detoxification pathway in C. autotrophica in order to alleviate Cd toxicity. Our study demonstrated that accumulation and subcellular distribution of Cd and PC synthesis can account for the inter-species differences in Cd sensitivity in marine phytoplankton.

Temperature-dependent sensitivity of a marine diatom to cadmium stress explained by subcelluar distribution and thiol synthesis.

This study examined the potential bioaccumulation and biochemical mechanisms (phytochelatin and other thiols induction) in the temperature-dependent sensitivity of a marine diatom Thalassiosira nordenskioeldii to cadmium (Cd) stress. A higher environmental temperature increased the sensitivity of diatoms to Cd toxicity. Either increased cellular Cd accumulation or a poorer detoxification ability was responsible for the higher concentration of metal-sensitive fraction (MSF)-Cd in the diatoms and subsequently the higher Cd sensitivity with increasing temperature. In addition, N-deficiency or glutathione depletion may partly explain the highest sensitivity at the highest tested temperature (30.5 degrees C). Although temperature affected the biochemical composition (e.g., the N/C ratio and phytochelatin induction), physiological processes (e.g., the growth rate, photosynthesis, Cd uptake, accumulation, and subcellular distribution) and the resulting differential tolerances, Cd concentration in MSF or organelles served as the best indicators of Cd toxicity in diatoms at different temperatures. Phytochelatins (PCs) were induced by increasing [Cd2+] and the significant relationship between the intracellular Cd and PC-SH concentration suggested that PC-SH is a biomarker for cellular metal stress. However, the intracellular Cd/ PC-SH ratio did not always explain the temperature-dependent metal tolerance. The functions of PCs other than metal chelation and detoxification need to be further examined.