Developmental toxicity and mechanism of polychlorinated biphenyls 126 and nano-polystyrene combined exposure to zebrafish larvae.

3,3',4,4',5-Pentachlorobiphenyl (PCB126) is the most toxic congener of dioxin-like polychlorinated biphenyls (DL PCBs), while nanoplastics (NPs) have recently emerged as significant marine pollutants, both posing threats to aquatic organisms and human health. They coexist in the environment, but their comprehensive toxicological effects remain unclear. In this study, zebrafish embryos were simultaneously exposed to PCB126 and 80-nanometer nanoplastyrene (NPS). Researchers utilized fluorescence microscopy, qPCR, histopathological examination, and transcriptomic sequencing to investigate the developmental toxicity of different concentrations of PCB126 and NPS individually or in combination on zebrafish embryos and larvae. Results indicate that the chorion significantly impedes the accumulation of NPS (p < 0.05). It is noteworthy that this barrier effect diminishes upon simultaneous exposure to PCB126. In this experiment, the semi-lethal concentration of PCB126 for larvae was determined to be 6.33 µg/L. Exposure to PCB126 induces various deformities, primarily mediated through the aryl hydrocarbon receptor (AHR). Similarly, exposure to NPS also activates AHR, leading to developmental impairments. Furthermore, transcriptomic sequencing revealed similar effects of PCB126 and NPS on the gene expression trends in zebrafish larvae, but combined exposure to both exacerbates the risk of cancer and induces more severe cardiac toxicity. At this level, co-exposure to PCB126 and NPS adversely affects the development of zebrafish larvae. This study contributes to a deeper understanding of the in vivo accumulation of DL polychlorinated biphenyls and microplastics in actual aquatic environments and their impact on fish development.

PCB169 exposure aggravated the development of non-alcoholic fatty liver in high-fat diet-induced male C57BL/6 mice.

Polychlorinated biphenyls (PCBs) are lipophilic environmental toxicants. Epidemiological studies have established a link between PCBs and both metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). Multiple studies have reported that exposure to both PCB156 and PCB126 among the 12 dioxin-like PCBs leads to the development of NAFLD. However, studies to elucidate whether PCB169 induces the development of NAFLD by constructing in vivo models have not been reported. Therefore, we evaluated the effects of exposure to PCB169 (5 mg/kg-bw) on hepatic lipid metabolism in C57BL/6 mice from control diet and high-fat diet cohorts. The results showed that PCB169 exposure reduced body weight and intraperitoneal fat mass in mice on the control diet, but the liver lipid levels were significantly increased, exacerbating NAFLD in mice on a high-fat diet. Through transcriptomics studies, it was found that PCB169 exposure induced significant up-regulation of Pparγ, Fasn, and Aacs genes involved in hepatic lipogenesis, as well as remarkable up-regulation of Hmgcr, Lss, and Sqle genes involved in cholesterol synthesis. Additionally, there was notable down-regulation of Pparα and Cpt1 genes involved in lipid ß-oxidation, leading to abnormal lipid accumulation in the liver. In addition, we found that PCB169 exposure significantly activated the Arachidonic acid metabolism, PPAR signaling pathway, Metabolism of xenobiotics by cytochrome P450, and Retinol metabolism pathways, and so on. Our study suggests that PCB169 can modify gene expression related to lipid metabolism, augument lipid accumulation in the liver, and further contribute to the development of NAFLD, thereby revealing the detrimental effects associated with PCB exposure on animal growth and metabolism.

Snake-shaped ePTFE nasal tip graft combined with conchal cartilage in Asian rhinoplasty: a retrospective cohort study.

BACKGROUND: Lacking a nasal tip projection is a common deformity of Asian nasals. Various commonly used nasal tip grafts require dissecting septal perichondrium, most of them are autologous cartilage with a nonintegrated design. A snake-shaped expanded polytetrafluoroethylene (ePTFE) nasal tip graft is an integrated, stable tip graft without any additional assembly and splicing, conforming to the nasal anatomy characteristics of Asians. METHOD: A retrospective study was performed on Asian patients who underwent rhinoplasty in the nasal tip at Peking University Third Hospital from 2015 to 2022. Nasal tip grafts were categorized into three groups: snake-shaped ePTFE combined with conchal cartilage (n = 15), only costal cartilage (n = 25), and only conchal cartilage (n = 17). Patients were excluded if their rhinoplasty did not involve any of the grafts above. Visual Analogue Scale, FACE-Q Nose, FACE-Q Nostril, Nasal Obstruction Symptom Evaluation scale, and Rhinoplasty Outcome Evaluation scale were used to evaluate the preoperative and postoperative results. RESULTS: Fifty-three (93.0%) cases had low nasal dorsum and 46 (80.7%) cases had short nose. There was no significant difference in complication rates among the three groups. The difference between preoperative and postoperative scale scores was statistically significant among the three groups (p < 0.05). Score improvements, including all scales, were the highest in the costal cartilage group and lowest in the conchal cartilage group. CONCLUSIONS: Snake-shaped ePTFE nasal tip grafts can be an effective integrated alternative that provides long-term safety and efficacy compared with traditional autogenous implants (conchal and costal cartilages).

Repair of Asian nasal subunit defects using nasolabial perforator flaps: A retrospective study.

BACKGROUND: The application of nasolabial perforator flap for nasal reconstruction has been reported previously with satisfactory outcomes, but the outcomes and risk factors of postoperative adverse events have been unclear to plastic surgeons. AIMS: To statistically analyze the effectiveness of the nasolabial perforator flap in nasal reconstruction and the risk factor of postoperative complications and re-operation. PATIENTS/METHODS: This retrospective study evaluated 58 Chinese patients who underwent nasal reconstruction with the nasolabial perforator flap from 2009 to 2021. The esthetic and blood supply outcomes were measured by plastic surgeons on a 5-point Likert scale. Binary logistic regression was used to determine the risk factors associated with postoperative complications and re-operation. RESULTS: The mean age of the cohort was 66.4 ± 2.0 years. The defect size ranged from 6.5 × 5.5 mm2 to 40 × 70 mm2 , and 48.3% of defects covered more than one nasal subunit. Venous congestion occurred in 4.9% of flaps, and the immediate overall postoperative score was 7.72/10. More than one nasal subunit of involvement was the risk factor associated with re-operation (p = 0.004), but no risk factor was associated with complications. CONCLUSIONS: The nasolabial perforator flap is reliable for nasal reconstruction with good esthetic outcomes and fewer complications. However, a large number of involved subunits may lead to multiple surgeries for flap trimming in easterners.

Rhodotorula mucilaginosa ZTHY2 Attenuates Cyclophosphamide-Induced Immunosuppression in Mice.

Rhodotorula mucilaginosa (R. mucilaginosa) can enhance the immune and antioxidant function of the body. However, whether R. mucilaginosa has an immunoregulatory effect on cyclophosphamide (CTX)-induced immunosuppressed animals remains to be clarified. In this study, the R. mucilaginosa ZTHY2 that we isolated from the coastal waters of the South China Sea previously was prepared in order to investigate its immunoprotective effect on CTX-induced immunosuppression in mice, and the effects were compared to those of Lactobacillus acidophilus (LA) (a well-known probiotic). Seventy-two male SPF mice were divided into six groups: The C group (control); IM group (immunosuppressive model group) (+CTX); Rl, Rm, and Rh groups (+CTX+low, medium, and high concentration of R. mucilaginosa, respectively); and PC (positive control) group (+CTX+LA). After a 28-day feeding trial, blood samples were taken for biochemical and serum immunological analysis, and the thymus and spleen were collected to analyze the organ index, lymphocyte proliferation and differentiation, and antioxidant capacity. The findings showed that R. mucilaginosa ZTHY2 improved the spleen and thymus indices, effectively attenuated immune organ atrophy caused by CTX, and enhanced the proliferation of T and B lymphocytes induced by ConA and LPS. R. mucilaginosa ZTHY2 promoted the secretion of cytokines and immunoglobulins and significantly increased the contents of IL-2, IL-4, IL-6, TNF-α, IFN-γ, IgA, IgG, IgM, CD4, CD8, CD19, and CD20 in serum. The proportion of CD4+, CD8+, CD19+, and CD20+ lymphocytes in spleen, thymus, and mesenteric lymph nodes were increased. In addition, R. mucilaginosa ZTHY2 reduced the reactive oxygen species (ROS) and malondialdehyde (MDA) levels and increased glutathione (GSH), total superoxide dismutase (SOD), and catalase (CAT) levels. Our results indicated that R. mucilaginosa ZTHY2 can significantly enhance the immune function of immunosuppressed mice, and improving antioxidant capacity thus attenuates CTX-induced immunosuppression and immune organ atrophy.

Cartilage 3D bioprinting for rhinoplasty using adipose-derived stem cells as seed cells: Review and recent advances.

Nasal deformities due to various causes affect the aesthetics and use of the nose, in which case rhinoplasty is necessary. However, the lack of cartilage for grafting has been a major problem and tissue engineering seems to be a promising solution. 3D bioprinting has become one of the most advanced tissue engineering methods. To construct ideal cartilage, bio-ink, seed cells, growth factors and other methods to promote chondrogenesis should be considered and weighed carefully. With continuous progress in the field, bio-ink choices are becoming increasingly abundant, from a single hydrogel to a combination of hydrogels with various characteristics, and more 3D bioprinting methods are also emerging. Adipose-derived stem cells (ADSCs) have become one of the most popular seed cells in cartilage 3D bioprinting, owing to their abundance, excellent proliferative potential, minimal morbidity during harvest and lack of ethical considerations limitations. In addition, the co-culture of ADSCs and chondrocytes is commonly used to achieve better chondrogenesis. To promote chondrogenic differentiation of ADSCs and construct ideal highly bionic tissue-engineered cartilage, researchers have used a variety of methods, including adding appropriate growth factors, applying biomechanical stimuli and reducing oxygen tension. According to the process and sequence of cartilage 3D bioprinting, this review summarizes and discusses the selection of hydrogel and seed cells (centered on ADSCs), the design of printing, and methods for inducing the chondrogenesis of ADSCs.

Isolation and genomic characterization of Klebsiella Lw3 with polychlorinated biphenyl degradability.

Bioremediation of sediment organic pollution has been intensely investigated, but the degradation of complex organic compounds, pesticide residues, and polychlorinated biphenyls (PCBs) remains poorly studied. In this study, sediments were collected from Zhanjiang Mangrove Reserve and inoculated in an inorganic salt medium using only biphenyl (BP) and PCBs as the carbon sources to obtain a PCB-degrading strain. A gram-negative bacterium that metabolized PCBs was isolated and identified as Klebsiella Lw3 by 16S rDNA phylogenetic analysis. Genomic sequencing showed that this bacterium possessed genes related to BP/PCB degradation, and its GC content was 58.2%; we identified 3326 cellular pathways. Gas chromatography-mass spectrometry was employed to test the PCB degrading ability; the results showed that the strain had a good degradation effect on PCB3 at concentrations of 5, 10, 20, 40, and 60 mg/L and that the final degradation rate was higher than 97% after 96 h. Interestingly, this strain showed good biodegradability of PCBs despite having no classical PCB degradation pathway, providing a new direction for Klebsiella research with practical significance for in situ bioremediation of PCB contamination. Overall, this study provides valuable insights into the genetic structure of PCB-degrading strains as well as eco-friendly and low-cost PCB degradation and lays a foundation for the discovery of new degradation pathways.

Effects of Aroclor 1254 on Intestinal Immunity, Metabolism, and Microflora in Zebrafish.

Polychlorinated biphenyls (PCBs) are widely distributed environmental toxicants, whose biological toxicity is magnified step by step through the transmission of the food chain. However, there is little research about the effect of PCBs on intestinal epithelial barrier function. In this experiment, the effects of PCB exposure on the intestines of zebrafish were evaluated. Animals were exposed to Aroclor 1254 (5 µg/L, 10 µg/L, 15 µg/L). After 21 days, the changes in histology, enzyme biomarkers, intestinal microorganisms, and metabolomics were detected. The inflammation and oxidative stress in the intestines of zebrafish were observed. Additionally, there were significant changes in intestinal microbiota and tissue metabolism, most of which were associated with oxidative stress, inflammation, and lipid metabolism. The results showed that PCBs exposure resulted in intestinal inflammation and oxidative stress in zebrafish.Moreover, intestinal metabolites and intestinal microflora of zebrafish were also disturbed. This study verified that exposure can lead to intestinal damage and changes in intestinal metabolic capacity and microorganisms, enlightening the consequences of PCB exposure.

Synthesis of MoS2 Nanochains by Electrospinning for Ammonia Detection at Room Temperature.

MoS2 nanochains were successfully prepared via facile electrospinning and a hydrothermal process. The morphology of MoS2 nanochains was evaluated by field emission scanning electron microscopy and high-resolution transmission electron microscopy. A slurry composed of the MoS2 nanochains was coated on a silver electrode to detect ammonia. The detection range of ammonia was between 25 and 500 ppm. MoS2 nanochains offered outstanding sensing response, repeatable reproducibility, and excellent selectivity with a detection limit of 720 ppb. The responsiveness of MoS2 nanochains to ammonia remained unchanged for 1 week.

Effects of Environmental and Spatial Variables on Bacteria in Zhanjiang Mangrove Sediments.

The bottom mud of mangroves contains numerous microbial groups that play an important role in the main ecological functions of the mangrove ecosystem. The diversity and functional and environmental factors related to microbial communities, in terms of the assembly process and in environmental adaptation of the abundance and rare bacterial communities in the mangrove ecosystem, have not been fully explored. We used 16S high-throughput sequencing and operational taxonomic unit analysis to compare the diversity and composition of bacterial communities in different tidal zones in the sediments of the Zhanjiang Gaoqiao Mangrove Nature Reserve, compare the ecological adaptation thresholds and phylogenetic signals of bacterial communities under different environmental gradients, and examine the factors affecting the composition of the bacterial community. The diversity of microbial species and structure and function of the mangrove sediments were affected by the environment, showing the trend: mid tide zone > climax zone > low tide zone. Organic matter content, oxygen content, pH, and total phosphorus were identified as important environmental factors determining the functional diversity of bacterial communities and survival, while pH influences species evolution. The abundant taxa showed a wider response threshold and stronger phylogenetic signals of ecological preference across environmental gradients compared to rare taxa. The abundant bacterial groups have broader environmental adaptability than rare bacterial groups, and different environmental factors affect different communities and functions in the mangrove ecological environment. These results elucidate the mechanism underlying the generation and maintenance of bacterial diversity in response to global environmental changes.

Effects of Microplastics on Microbial Community in Zhanjiang Mangrove Sediments.

Microplastics are easily consumed by marine animals, thereby entering the food chain and endangering animal health. However, there are few studies focusing on the effects of microplastics in mangrove sediments on microbial communities. In order to study the influence of microplastics on microorganisms, microplastics and microorganisms were extracted from Zhanjiang (Guangdong Province, China) mangrove sediments and analyzed. The results showed that there were differences in Shannon and Simpson indices of the microbial community in microplastics (p < 0.05), and there were also differences between JG30_KF_CM45 and Natranaerovirga at the genus level, indicating that microplastics may affect the diversity and composition of microorganisms in sediments. In addition, FAPROTAX function prediction analysis showed that microplastics may affect the nitrification of microbial communities. The results from this study indicate that microplastics affected the diversity and richness of microorganisms in mangrove sediments, which provides an experimental basis for the relationship between microplastics and microorganisms.

Institutional investors and cost of capital: The moderating effect of ownership structure.

Guiding institutional investors to actively participate in corporate governance is a hot issue to improve the internal governance of China's listed companies. This study seeks to provide a comprehensive understanding of the mechanism that underlies the governance effects of the heterogeneity of institutional investors on the cost of capital, and the influence of ownership structure on the relationship between them. Using an unbalanced panel data on A-share listed companies of Shanghai and Shenzhen in China's capital market during the 2014-2019 period, this study reveals how institutional investors with longer holding period and higher shareholding ratio are negatively associated with the cost of capital in China's capital market. Furthermore, this study successfully confirms the moderating effect of ownership structure in the relationship between institutional investors and the cost of capital. China's state-owned enterprises are more likely to introduce improvements at the corporate governance level, and ownership concentration weakens the negative influence of institutional investors on the cost of capital. The research contributes to a deeper understanding of the impacts of institutional investor's heterogeneity and ownership structure on the cost of capital in China. In the process, the study yields useful implications for the theory and practice of corporate governance.

Efficient adsorption removal of anionic dyes by an imidazolium-based mesoporous poly(ionic liquid) including the continuous column adsorption-desorption process.

The mesoporous poly(N,N'-methylene-bis(1-(3-vinylimidazolium)) chloride), labeled as PDVIm-Cl, with double anions (Cl-) and low monomer molecular weight was synthesized and applied in the adsorption of anionic dyes (acid orange 7 (AO7), sunset yellow (SY), reactive blue 19 (RB19), congo red (CR)). Due to the mesoporous structure, abundant Cl- and positively charged imidazole rings, the poly(ionic liquid) (PIL) exhibited superior adsorption ability towards anionic dyes. What is more, the RB19 adsorption by PDVIm-Cl could achieve the highest capacity (2605 ± 254 mg g-1) which was nearly twice higher than the maximum adsorption capacity of the previously reported materials. All the adsorption kinetic data and isotherms fitted well with the pseudo second-order model and Langmuir-Freundlich model. To better explore the practical potential of the PIL for dye adsorption, the adsorption under different pH values and column adsorption performances were also evaluated. Results showed that PDVIm-Cl exhibited high removal efficiencies for anionic dyes over a wide pH range (2-10). Also, the great reusability could be well demonstrated by the achievable continuous column adsorption-desorption process. It is worth mentioning that the regeneration could be realized with very little desorbent which was far less than the adsorption volume flowing through the column and the desorption efficiency was well maintained after three consecutive cycles. At last, the adsorption mechanism was explored by experiments combined with quantum chemical calculations and showed anionic dyes adsorption by PDVIm-Cl was a joint process dominated by the ion exchange, electrostatic interaction, hydrogen bond and π-π stacking.

Removal of anionic hexavalent chromium and methyl orange pollutants by using imidazolium-based mesoporous poly(ionic liquid)s as efficient adsorbents in column.

Poly(ionic liquid)s (PILs) are attractive for their various applications, but the use of porous PILs have rarely been reported in anionic pollutants removal via ion-exchange by column. Herein, we report a serial of crosslinked imidazolium-based mesoporous PILs with Cl- and Br- as anions for hexavalent chromium (Cr(VI)) and methyl orange (MO) removal. Among them, PDVIm-Cl-SCD, from the free-radical polymerization of a dicationic monomer (N,N'-methylene-bis(1-(3-vinylimidazolium)) chloride, DVIm-Cl) and further supercritical carbon dioxide drying (SCD), displayed a very high sorption capacity (328.2 mg g-1 at 25 °C) and excellent utilization of adsorption sites (UOA, 86.2%) towards Cr(VI), and an unprecedentedly high sorption capacity (1615.0 mg g-1 at 25 °C) with a UOA of 67.4% to MO. Moreover, PDVIm-Cl-SCD also exhibited a broad pH range, excellent regeneration and remarkable reusability. Regarding to Cr(VI) removal, the volume of saturated KCl aqueous used for regenerating the Cr(VI) saturated PDVIm-Cl-SCD column (7.5-9.5 mL) was much less than the volume of treated Cr(VI) solution (160-200 mL). For MO removal, the volume of saturated NaCl solution used for regenerating the MO saturated PDVIm-Cl-SCD column (10.5-13.5 mL) was also much less than the volume of treated MO solution (220-235 mL), implying the great potential of PDVIm-Cl-SCD in sustainable wastewater treatment.

Characterization of the substrate specificity of the inositol 5-phosphatase SHIP1.

SHIP1 is an inositol 5-phosphatase which is well established for its tumour suppressor potential in leukaemia. Enzymatically, two SHIP1 substrates, PtdIns(3,4,5)P3 and Ins(1,3,4,5)P4 have been identified to date. Additional substrates were found for the homologue SHIP2. In this study, we identified new inositol phosphate (InsP) substrates of SHIP1 by metal dye detection high-performance liquid chromatography and compared the substrate profiles of SHIP1 and SHIP2. We were able to verify Ins(1,3,4,5)P4 as a substrate of SHIP1 and interestingly found Ins(1,2,3,4,5)P5 and Ins(2,3,4,5)P4 to be preferably used as substrates and Ins(1,4,5,6)P4 and Ins(2,4,5,6)P4 to be weak substrates. All of those except Ins(2,3,4,5)P4 are also known substrates of SHIP2 indicating a possible exclusive role of Ins(2,3,4,5)P4 hydrolysis for SHIP1 but not SHIP2 function.

A novel 6-pyrophosphorylating IP6 kinase (IP6-6K) discovered in the protozoon Trichomonas vaginalis.

The parasitic protozoon Trichomonas vaginalis is the pathogen of trichomoniasis, the most common non-viral, sexually transmitted disease in humans. Inositol phosphates function in the pathomechanisms of a number of human pathogenic protozoa. Recent findings point to a role of inositol phosphates in T. vaginalis' adaption to oxygen exposure during change of host. Six inositol phosphate kinase genes (tvip6k1-4, tvipk1-2) were identified in the T. vaginalis genome by us all coding for proteins containing canonical sequence motifs of the major group of animal inositol phosphate kinases (PDKG, SSLL, DFG/A). When characterizing the purified protein product of tvip6k1, we discovered that the major activity of the highly active enzyme (˜2 µmol/min/mg) is a conversion of InsP6 to 6PP-InsP5 and not 5PP-InsP5 as by animal isoforms. Thus TvIP6K1 is a novel IP6-6K. The enzyme also converts Ins(1,3,4,5,6)P5 to products pyrophosphorylated both at 6- and 4-phosphate still having a free 5-hydroxyl. In addition, the enzyme has a minor selectivity to phosphorylate the 3-OH in Ins(1,2,4,5)P4 and Ins(1,2,4,5,6)P5. To present knowledge this novel enzyme is restricted to protozoa. Since its structure is predicted to be distinctly different from animal IP6K (IP6-5K) forms, TvIP6-6K may become a promising target to search for novel trichomoniasis specific drugs.

Inositol hexakisphosphate increases the size of platelet aggregates.

The inositol phosphates, InsP5 and InsP6, have recently been identified as binding partners of fibrinogen, which is critically involved in hemostasis by crosslinking activated platelets at sites of vascular injury. Here, we investigated the putative physiological role of this interaction and found that platelets increase their InsP6 concentration upon stimulation with the PLC-activating agonists thrombin, collagen I and ADP and present a fraction of it at the outer plasma membrane. Cone and plate analysis in whole blood revealed that InsP6 specifically increases platelet aggregate size. This effect is fibrinogen-dependent, since it is inhibited by an antibody that blocks fibrinogen binding to platelets. Furthermore, InsP6 has only an effect on aggregate size of washed platelets when fibrinogen is present, while it has no influence in presence of von Willebrand factor or collagen. By employing blind docking studies we predicted the binding site for InsP6 at the bundle between the γ and ß helical subunit of fibrinogen. Since InsP6 is unable to directly activate platelets and it did not exhibit an effect on thrombin formation or fibrin structure, our data indicate that InsP6 might be a hemostatic agent that is produced by platelets upon stimulation with PLC-activating agonists to promote platelet aggregation by supporting crosslinking of fibrinogen and activated platelets.

Simultaneous determination of six coptis alkaloids in urine and feces by LC-MS/MS and its application to excretion kinetics and the compatibility mechanism of Jiao-Tai-Wan in insomniac rats.

Jiao-Tai-Wan (JTW) is a well-known traditional Chinese medicine prescription composed of Rhizoma Coptidis (RC) and Cortex Cinnamon (10:1, g/g). It has been used to treat insomnia in China for centuries. This study investigates the excretion properties of coptis alkaloids from RC and JTW in normal and insomniac rats, and it examines the compatibility mechanism for this prescription. A new liquid chromatography-tandem mass spectrometry method was developed for the simultaneous determination of six alkaloids - berberine, epiberberine, coptisine, jatrorrhizine, palmatine and magnoflorine - in rat urine and feces. The normal and model rats were orally treated with RC and JTW powder at a dosage containing 3.0 g kg-1  day-1 RC once per day for 7 days. Briefly, the results showed that the cumulative amounts of urinary and fecal excretion of the six alkaloids were significantly different in the pathological condition, as well as in compatibility. In normal rats, the urinary and fecal excretion of coptis alkaloids, especially berberine, coptisine and palmatine, increased significantly in the JTW group compared with the RC group, while the urinary and fecal excretion of six alkaloids decreased in insomniac rats. These data suggested that pathological conditions might have a notable influence on the excretion of alkaloids in rats, and demonstrated that the compatibility could promote better therapeutic effects through the accumulation of alkaloids in the body. These results might explain the compatibility of JTW.

The oral bioavailability, excretion and cytochrome P450 inhibition properties of epiberberine: an in vivo and in vitro evaluation.

Epiberberine (EPI) is a novel and potentially effective therapeutic and preventive agent for diabetes and cardiovascular disease. To evaluate its potential value for drug development, a specific, sensitive and robust high-performance liquid chromatography-tandem mass spectrometry assay for the determination of EPI in rat biological samples was established. This assay was used to study the pharmacokinetics, bioavailability and excretion of EPI in rats after oral administration. In addition, a cocktail method was used to compare the inhibition characteristics of EPI on cytochrome P450 (CYP450) isoforms in human liver microsomes (HLMs) and rat liver microsomes (RLMs). The results demonstrated that EPI was rapidly absorbed and metabolized after oral administration (10, 54 or 81 mg/kg) in rats, with Tmax of 0.37-0.42 h and T1/2 of 0.49-2.73 h. The Cmax and area under the curve values for EPI increased proportionally with the dose, and the oral absolute bioavailability was 14.46%. EPI was excreted mainly in bile and feces, and after its oral administration to rats, EPI was eliminated predominantly by the kidneys. A comparison of the current half-maximal inhibitory concentration and Ki values revealed that EPI demonstrated an obvious inhibitory effect on CYP2C9 and CYP2D6. Furthermore, its effect was stronger in HLM than in RLM, more likely to be a result of noncompetitive inhibition.

Histopathological changes in zebrafish embryos exposed to DLPCBs extract from Zhanjiang coastal sediment.

Dioxin-like polychlorinated biphenyls (DLPCBs) are ubiquitous persistent pollutants that cause adverse effects in many environmental organisms. DLPCBs in marine sediments can be absorbed by benthic organisms, bioaccumulate, and biomagnify through the food chain and threaten animal and human health. There are no reports of DLPCBs concentrations in the Zhanjiang Gulf seabed. This study was designed to investigate the concentration of DLPCBs in the Zhanjiang coastal sediment and histopathological changes in zebrafish (Diano rerio) embryos exposed to environmentally relevant concentrations of DLPCBs. Of the five sites selected, two sites TS and JSW contained DLPCBs at concentrations of 0.08 and 22.54 ng/g dry sediment, respectively. Two groups of zebrafish embryos were used. One group was exposed to 3.75, 7.5, 15, 30, and 60 mg/ml of DLPCBs extracted from the sediments sampled from the TS site and the second group to 4.375, 8.75, 17.5, 35, and 70 mg/ml of DLPCBs from JSW site from 0.75 h post-fertilization (hpf) to 96 hpf. The zebrafish exposed to 60 and 70 mg/ml of DLPCBs at 96 hpf displayed gross histopathological changes with cardiac lesions including pericardial edema being the most deleterious. Other changes observed were hydropic degeneration of gill filaments and hepatocytes, loss of intestinal folds, and uninflated swim bladder. It appears that only a few sites of the Zhanjiang gulf are contaminated with DLPCBs. This is the first report of histopathological changes in the gills, hepatocytes, intestines, heart, and the swim bladder in zebrafish embryos exposed to DLPCBs from a coastal sediment. Further studies with sampling at different stages of development are required to identify which organ/tissue is most sensitive to DLPCBs.