Developmental and behavioral toxicity assessment of opicapone in zebrafish embryos.

The use of clinical psychoactive drugs often poses unpredictable threats to fetal development. Catechol-O-methyltransferase (COMT) is a key enzyme that regulates dopamine metabolism and a promising target for modulation of cognitive functions. Opicapone, a newly effective third-generation peripheral COMT inhibitor, is used for the treatment of Parkinson's disease (PD) and possibly to improve other dopamine-related disorders such as alcohol use disorder (AUD) and obsessive-compulsive disorder (OCD). The widespread use of opicapone will inevitably lead to biological exposure and damage to the human body, such as affecting fetal development. However, the effect of opicapone on embryonic development remains unknown. Here, zebrafish larvae were used as an animal model and demonstrated that a high concentration (30 µM) of opicapone exposure was teratogenic and lethal, while a low concentration also caused developmental delay such as a shortened body size, a smaller head, and reduced locomotor behaviors in zebrafish larvae. Meanwhile, opicapone treatment specifically increased the level of dopamine (DA) in zebrafish larvae. The depletion response of the total glutathione level (including oxidized and reduced forms of glutathione) and changed antioxidant enzymes activities in zebrafish larvae suggest oxidative damage caused by opicapone. In addition, enhanced glutathione metabolism and cytokine-cytokine receptor interaction were found in zebrafish larvae treated with opicapone, indicating that opicapone treatment caused an oxidation process and immune responses. Our results provide a new insight into the significant developmental toxicity of opicapone in zebrafish larvae.

Source profile and health risk assessment of PM2.5 from coal-fired power plants in Fuxin, China.

In order to improve and establish the localized source profile of PM2.5 in Fuxin, the ashes under dust catcher were collected from four typical coal-fired power plants in Fuxin and twenty-eight components were measured. The source profile of PM2.5 in the soot of the four coal-fired power plants was established. SO42- was the most abundant component in the PM2.5 of the soot of the four coal-fired power plants, followed by Ca2+ and organic carbon (OC). The content of element components in PM2.5 smoke ranges from 5.06 to 10.97%, the content of ionic components ranges from 36.53 to 48.59%, and the total carbon content ranges from 9.43 to 11.36%. The divergence coefficient of PM2.5 source profile in Fuxin coal burning smoke is mostly similar to that of Fushun, whereas the divergence coefficient of Colorado reaches 0.65, indicating that Fuxin coal burning power plant smoke has no similarity to Colorado. The order of the geological accumulation index of Ni, Cu, V, Mn, and Cr was Cr (4.58) > Mn (4.42) > V (4.38) > Cu (4.09) > Ni (4.06), showing a heavy pollution level. The health risk assessment model recommended by the USEPA was used to assess the health risk of heavy metals in soot of coal-fired power plants, and the non-carcinogenic risk values of As for children and adults were 45.7 and 4.90, respectively. The carcinogenic risk values of Cr for adults and children were the highest, with values of 3.66 × 10-5 and 2.06 × 10-5, respectively, followed by As.

Efficacy and safety of doublet versus single agent as salvage treatment for metastatic breast cancer pretreated with anthracyclines and taxanes: a systematic review and meta-analysis.

AIM: To perform a systematic review and meta-analysis of randomized controlled trials to compare the efficacy and safety of doublet versus single agent as salvage treatment for pretreated metastatic breast cancer. METHODS: A comprehensive literature search was performed to identify relevant randomized controlled trials (RCTs). All clinical studies were independently identified by two authors for inclusion. Demographic data, treatment regimens, objective response rate (ORR), and progression-free survival (PFS) and overall survival (OS) were extracted and analyzed using Comprehensive MetaAnalysis software (Version 2.0). RESULTS: Thirteen RCTs involving 4878 pretreated metastatic breast cancer patients were ultimately identified. The pooled results demonstrated that doublet combination therapy significantly improved ORR (RR 1.13, 95% CI: 1.01-1.27, p < .001) and PFS (hazard ration [HR] 0.83, 95% CI: 0.73-0.96, p = .011), but not OS (HR 0.93, 95% CI: 0.86-1.01, p = .065). Similar results were observed in sub-group analysis according to treatment regimens. Additionally, more incidences of grade 3 or 4 myelosuppression toxicities nausea and fatigue were observed in doublet combination therapy. CONCLUSIONS: In comparison with a single agent alone, doublet combination therapy as salvage treatment for pretreated metastatic breast cancer patients significantly improves ORR and PFS, but not OS. Further studies are recommended to identify patients who will most likely benefit from the appropriate doublet combination therapy.

Further investigation of nanostructured lipid carriers as an ocular delivery system: in vivo transcorneal mechanism and in vitro release study.

This study was designed to provide further understanding of transcorneal mechanism of nanostructured lipid carriers (NLC). NLC labeled with fluorescent marker rhodamine B or coumarin-6 were produced by a melt emulsification method. By confocal laser scanning microscopy (CLSM), the interaction of NLC with corneal epithelia was traced and evaluated in rabbits in vivo. Thermal stability of the markers and the amorphous state were detected using thermogravimetric analysis (TGA) and differential scanning calorimeter (DSC). The labeled NLC were characterized to be solid spherical in shape with an average diameter of 70 nm and zeta potential of -8 mV by transmission electron microscopy and dynamic light scattering, respectively. CLSM results demonstrated NLC were not directly internalized by corneal epithelia, whereas the markers themselves transferred from NLC to corneal epithelia with subsequent staining of intracellular lipophilic compartments. Furthermore, the in vitro release study using liposome dispersions as mimic biomembranes demonstrated an efficient transfer of fluorescence marker into the liposomes. This implied the deceptive particle uptake was due to a collision-induced process, during which the rapid transfer of fluorescence marker occurred by forming a complex between the nanoparticles and the biomembranes. Thus, these evidences provide further insights into NLC as an ocular delivery system.

[Cataplasma of traditional Chinese medicine].

The TCM (traditional Chinese medicine) transdermal plaster (also known as "cataplasma") are flexible adhesive patches used for treatment of pain, resulted from arthritis, sprain and bruise, tendovaginitis, lumbar spine protrude, neuralgia, hyperosteogeny ache, abdominal discomfort and metastatic cancer, etc. Since the 1980's, investigators in China have used this modern patch delivery system for herbal drugs and obtained satisfactory results especially from the treatment of various types of pain associated with bone diseases, abdominal discomfort, and tumors, etc. The production of TCM cataplasma was successfully scaled up in early 90's and the commercial product line for an antirheumatic agent was first established in Shanghai by Leiyunshang Group. Thus far, a number of products in the form of TCM cataplasma became commercially available in the market, and clinical investigations with these products indicated that topically applicable herbal preparations, especially in the form of cataplasma, are preferred formulations with respect to the treatment comfort of the patient. Compared to the traditional preparations which utilize rubber and rosin as adhesives, cataplasma is advantageous in that the lipophilic and hydrophilic ingredients of the herbal extracts are solubilized and then "gellified" with the organic polymers, and that the drug matrix containing up to 40%-70% of water serves as a "drug reservoir" that will sustain the quick and continuous release of herbal ingredients over several days across the skin. While there are conventional remedies for palliation of pain and discomfort associated with bone diseases or cancers, administration of oral medicinal herbs combined with topical agents such as TCM cataplasma may significantly alleviate the symptoms and improve their quality of life. This article provides a review on three aspects, which include the process development, characteristics and developmental status of TCM cataplasma, and future development of such a technology.