Phase Preparation of Xiao-chai-hu Decoction and its Pharmacodynamics of Acute Liver Injury.

BACKGROUND: Self-emulsifying nano-phase of traditional Chinese medicine are a research hotspot. Xiao-Chai-Hu decoction is a commonly used compound decoction in clinical practice, which is of great research significance. The aim of this study was to isolate and characterize the self-emulsifying nano-phase and other phases of Xiao-Chai-Hu decoction, and to study the effects of each phase on acute liver injury. METHODS: The liquid medicine was prepared employing centrifugation followed by dialysis. Single- factor investigation methodology was utilized to optimize the preparation parameters for both phases. Characterization of the formulated phase involved analyses such as surface morphology assessment, measurement of nanoparticle size and Zeta potential using an analyzer, observation of the Tyndall effect, conducting diffusion and dilution tests, examination under a microscope, and structural visualization via transmission electron microscopy (TEM). Furthermore, an acute liver injury model was established in rats through intraperitoneal injection of D-Galactosamine (D-Gal- N). To assess hepatic function and oxidative stress status, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), superoxide dismutase (SOD) activity, and malondialdehyde (MDA) content in liver tissue were quantified. The liver coefficients for each group were calculated as an additional parameter. For histopathological evaluation, liver tissue sections from the experimental group were stained with Hematoxylin and Eosin (H&E) and examined microscopically under light conditions. These revisions aim to enhance clarity, correct minor grammatical errors (such as capitalization of "HE" to "H&E"), and ensure a smoother flow of information without altering the scientific content of your original text. RESULTS: Successful establishment and separation of four distinct phases were achieved, including the self-emulsifying nano-phase, precipitation phase, suspension phase, and true solution phase. The self-emulsifying nano-phase was characterized as spherical particles with an average diameter of approximately 100 nm. Pharmacodynamic assessments revealed that both Xiao-Chai-Hu decoction and its self-emulsifying nano-phase significantly reduced liver coefficients and alanine aminotransferase (ALT) levels compared to controls (P<0.05). However, no statistically significant differences were observed in regards to aspartate aminotransferase (AST) concentrations, malondialdehyde (MDA) content, or superoxide dismutase (SOD) activity between the treatment groups and control (P>0.05). These findings indicate that both Xiao-Chai-Hu decoction and its self-emulsifying nano-formulation ameliorated D-GalN-induced acute liver injury, albeit without statistically distinguishable efficacy between them (P>0.05). CONCLUSION: The presence of a self-emulsifying nano-phase within Xiao-Chai-Hu decoction is confirmed, and this nano-phase emerges as a therapeutically efficacious component in mitigating acute liver injury.

Investigating Xiaochaihu Decoction's fever-relieving mechanism via network pharmacology, molecular docking, dynamics simulation, and experiments.

Xiaochaihu Decoction（XCHD）is a classic prescription for the treatment of fever, but the mechanism is not clear. In this study, We elucidated the mechanism of action through network pharmacology and molecular docking. A rat fever model was established to verify the prediction results of network pharmacology. The analysis revealed that 120 intersection targets existed between XCHD and fever. The TP53, STAT3, RELA, MAPK1, AKT1, TNF and MAPK14 as potential core targets of XCHD in fever treatment. GO and KEGG pathway enrichment analyses indicated that XCHD may act through pathways such as the AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, IL-17 signaling pathway. Molecular docking results demonstrated that quercetin, kaempferol, ß-sitosterol, stigmasterol and baicalein exhibited strong binding activity to key targets. Animal experiments showed that XCHD significantly reduced body temperature and levels of IL-1ß, IL-6, TNF-α, NO, PGE2, and cAMP in rats with fever. Importantly, no significant difference was observed between the XCHD self-emulsifying nano phase plus suspension phase and XCHD group. XCHD exerts its therapeutic effects on fever through a multi-ingredient, multi-target, and multi-pathway approach.

Preparation, characterization, and liver targeting evaluation of a novel sustained-release brucine self-assembled micelle mediated by glycyrrhetinic acid.

Background: Cancer is a serious threat to human life, health and social development. In recent years, nanomicelles, as an emerging drug carrier material, have gradually entered people's field of vision because of their advantages of improving bioavailability, maintaining drug levels, reducing systemic side effects and increasing drug accumulation at target sites. Methods: In this study, B-GPSG nano-micelles were prepared by film dispersion hydration method using brucine as model drug and glycyrrhetinic acid-polyethylene glycol-3-methylene glycol-dithiodipropionic acid-glycerol monostearate polymer as nano-carrier. The preparation process, characterization, drug release in vitro, pharmacokinetics and liver targeting were investigated. Results: The results showed that the range of particle size, polydispersion index and Zeta potential were 102.7 ± 1.09 nm, 0.201 ± 0.02 and -24.5 ± 0.19 mV respectively. The entrapment efficiency and drug loading were 83.79 ± 2.13% and 12.56 ± 0.09%, respectively. The drug release experiments in vitro and pharmacokinetic experiments showed that it had obvious sustained release effect. For pharmacokinetics study, it shows that both the B-GPSG solution group and the B-PSG solution group changed the metabolic kinetic parameters of brucine, but the B-GPSG solution group had a better effect. Compared with the B-PSG solution group, the drug was more prolonged in rats. The half-life in the body and the retention time in the body of B-GPSG are more helpful to improve the bioavailability of the drug and play a long-term effect. The tail vein injection results of mice indicate that B-GPSG can target and accumulate brucine in the liver without affecting other key organs. Cell uptake experiments and tissue distribution experiments in vivo show that glycyrrhetinic acid modified nano-micelles can increase the accumulation of brucine in hepatocytes, has a good liver targeting effect, and can be used as a new preparation for the treatment of liver cancer. Conclusion: The B-SPSG prepared in this experiment can provide a new treatment method and research idea for the treatment of liver cancer.

A novel nano-drug delivery system of glycyrrhetinic acid-mediated intracellular breakable brucine for enhanced anti-hepatitis B efficacy.

Background: Glycyrrhetinic acid-mediated brucine self-assembled nanomicelles enhance the anti-hepatitis B properties of brucine by improving its water solubility, short half-life, toxicity, and side effects. Brucine (B) is an indole alkaloid extracted from the seeds of Strychnos nux-vomica (Loganiaceae). Purpose: To assess the efficacy of the Brucine-Glycyrrhetnic acid-Polyethylene glycol-3,3'-dithiodipropionic acid-Glycerin monostearate (B-GPSG) in treating hepatitis B, its potential to protect against acute liver injury caused by d-galactosamine and its anti-hepatoma activities were studied. Research Design: The concentration of B-GPSG used in the in vivo and in vitro experiments was 0.63 mg/mL. The rats injected with d-GalN (450 mg/kg) were used as liver injury models. The rats were separated into normal, model, positive, positive control, B-PSG and B-GPSG groups. Hepatoma cells expressing HBV HepG2.2.15 were used for in vitro experiments. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, plate cloning, Hoechst staining and flow cytometry were conducted to explore the mechanism of B-GPSG against hepatitis B. Results: Compared with the model group, the liver coefficient of B-GPSG group decreased (4.59 ± 0.17 vs 5.88 ± 0.42), the content of MDA in rat liver homogenate decreased (12.54 ± 1.81 vs 23.05 ± 2.98), the activity of SOD increased, the activity of ALT and AST in rat serum decreased. In vitro, the IC50 values of B-GPSG group decreased. B-GPSG group effectively inhibited the proliferation and migration of HepG2.2.15 cells. Conclusions: The hepatoprotective effects of B-GPSG nanomicelles, which are attributed to their GA-mediated liver targeting and synergistic actions with brucine, suggest their therapeutic potential against hepatitis B. This development opens up new possibilities for the application of traditional Chinese medicine and nanomedicine in anti-hepatitis B.

Preparation, characterization, and in vivo evaluation of glycyrrhetinic acid-mediated nano-drug delivery system co-loaded with syringopicroside and hydroxytyrosol.

This study aimed to create a glycyrrhetinic acid (GA)-mediated, multi-component, self-assembled nano-drug delivery system co-loaded with syringopicroside (S) and hydroxytyrosol (H) obtained from Syringa Linn by synthesizing a GA-polyethylene glycol-poly (lactic acid-co-glycolic acid) (GPP) nanoparticle delivery carrier to actively target the liver. The nanoparticles were optimized using the central composite design. Nanoparticle characterization, cytotoxicity, pharmacodynamics, and tissue distribution study were performed. The optimized SH-GPP nanoparticle was a white solid powder, which was safe and non-toxic. The particle size and Zeta potential of the nanoparticles were 101.5 ± 3.18 nm and -23.3 ± 0.82 mV, respectively. The polydispersity index value (PDI) was 0.190 ± 0.005; the particle size distribution was comparatively uniform. The average total encapsulation efficiency of the optimized SH-GPP nanoparticle was 50.26% ± 1.29%, and drug loading was 15.47% ± 0.39%. After S and H were arranged into nanoparticles, the proliferation inhibition of HepG2.2.15 cells was improved, and the aim of drug-loaded synergism between GPP and SH was achieved. The GA-mediated nanoparticles were better targeted, were retained longer in vivo, and had higher concentrations in the liver than the unmodified nanoparticles. These nanoparticles have the potential to be a new effective anti-hepatitis B treatment and have great research potential in clinical treatment.

[Research progress on traditional Chinese medicine compounds combined with external therapy in treatment of hyperplasia of mammary glands].

Hyperplasia of mammary glands is a benign breast disease with disordered breast structure. Nowadays, the incidence rate of breast hyperplasia in women is increasing year by year, and the etiology is related to the imbalance of estrogen and progesterone in the body. The symptoms include breast pain, breast nodules, or nipple discharge, which can develop into breast cancer in the context of psychological pressure. Therefore, it is timely and effectively necessary for people to treat the symptoms. At present, traditional Chinese medicine(TCM) often treats breast hyperplasia by oral drug, external application, acupuncture, moxibustion, and massage, while western medicine often uses hormone therapy or surgery. TCM can regulate hormone levels to treat breast hyperplasia. Acupuncture, moxibustion, and other methods can stimulate acupoints to reduce breast lumps. However, since TCM is easy to produce hepatorenal toxicity after long-term use and simple external treatment is slow to take effect, rapid and effective treatment is difficult to be achieved. Although western medicine can inhibit the disease, it is easy to produce toxic and side effects if taken for a long time. In addition, surgery can only remove the focus and the recurrence rate is high. Some studies have found that the combination of oral and external use of TCM compounds has a significant effect, with mild toxic and side effects, few adverse reactions, and a low recurrence rate. Based on the relevant literature in recent years, this article reviewed the combination of oral and external treatment of TCM in the treatment of hyperplasia of mammary glands, discussed the effectiveness, clinical evaluation indexes, and mechanism, and pointed out the existing shortcomings to explore a comprehensive therapy worthy of clinical application.

Anti-inflammatory effect and antihepatoma mechanism of carrimycin.

BACKGROUND: New drugs are urgently needed for the treatment of liver cancer, a feat that could be feasibly accomplished by finding new therapeutic purposes for marketed drugs to save time and costs. As a new class of national anti-infective drugs, carrimycin (CAM) has strong activity against gram-positive bacteria and no cross resistance with similar drugs. Studies have shown that the components of CAM have anticancer effects. AIM: To obtain a deeper understanding of CAM, its distribution, metabolism and anti-inflammatory effects were assessed in the organs of mice, and its mechanism of action against liver cancer was predicted by a network pharmacology method. METHODS: In this paper, the content of isovaleryl spiramycin III was used as an index to assess the distribution and metabolism of CAM and its effect on inflammatory factors in various mouse tissues and organs. Reverse molecular docking technology was utilized to determine the target of CAM, identify each target protein based on disease type, and establish a target protein-disease type network to ascertain the effect of CAM in liver cancer. Then, the key action targets of CAM in liver cancer were screened by a network pharmacology method, and the core targets were verified by molecular docking and visual analyses. RESULTS: The maximum CAM concentration was reached in the liver, kidney, lung and spleen 2.5 h after intragastric administration. In the intestine, the maximum drug concentration was reached 0.5 h after administration. In addition, CAM significantly reduced the interleukin-4 (IL-4) levels in the lung and kidney and especially the liver and spleen; moreover, CAM significantly reduced the IL-1ß levels in the spleen, liver, and kidney and particularly the small intestine and lung. CAM is predicted to regulate related pathways by acting on many targets, such as albumin, estrogen receptor 1, epidermal growth factor receptor and caspase 3, to treat cancer, inflammation and other diseases. CONCLUSION: We determined that CAM inhibited inflammation. We also predicted the complex multitargeted effects of CAM that involve multiple pathways and the diversity of these effects in the treatment of liver cancer, which provides a basis and direction for further clinical research.

A novel strategy against hepatitis B virus: Glycyrrhetnic acid conjugated multi-component synergistic nano-drug delivery system for targeted therapy.

It is well known that Glycyrrhetnic acid (GA) has significant liver-targeting and anti-inflammatory effects. Syringopicroside (SYR) and Hydroxytyrosol (HT), the active components of the Chinese herb Syringa oblata Lindl, have earned great reputation for their potential in preventing or treating viral hepatitis type B. Therefore, we loaded SYR and HT into GA-conjugated PEG-PLGA, so that they could target the liver in additional to exerting their own pharmacological effects in a synergistic. However, the in vivo targeting and the low bioavailability of SYR and HT pose a huge challenge. Therefore, we synthesized GA-conjugated multi-component nano-drug delivery system (SH-GPP). SH-GPP had a regular spherical shape with a uniform size distribution of 110.5 ± 3.18 nm. We further evaluated the effects of SH-GPP in vitro and in vivo. In the in vivo experiment, we evaluated the following parameters: the serum ALT and AST values; liver tissue homogenate MDA and SOD; HE staining of the pathological liver sections; and the liver coefficient. In the in vitro studies, the following parameters were evaluated: cellular uptake of SH-GPP; wound healing/scratch assay; cellular apoptosis; cell cycle; HBsAg; and HBeAg content. SH-GPP had better anti-hepatitis B effect than Syringopicroside and hydroxytyrosol (SH) and NPP alone. The targeting ability of GA enabled HT and SYR in GPP to reach the liver accurately, and played a synergistic role to maximize their therapeutic effects. This study provides a novel strategy against hepatitis B virus, and also provides a feasible scheme for improving the low bioavailability of the active components of traditional Chinese medicine.

A review on plant polysaccharide based on drug delivery system for construction and application, with emphasis on traditional Chinese medicine polysaccharide.

Carbohydrate polymers with unique chemical composition, molecular weight and functional chemical groups show multiple potentials in drug delivery. Most carbohydrate polymers such as plant polysaccharides exhibit advantages of biodegradability, ease of modification, low immunogenicity and low toxicity. They can be conjugated, cross-linked or functionally modified, and then used as nanocarrier materials. Polysaccharide drug delivery system can avoid the phagocytosis of the reticuloendothelial system, prevent the degradation of biomolecules, and increase the bioavailability of small molecules, thus exerting effective therapeutic effects. Therefore, they have been fully explored. In this paper, we reviewed the construction methods of drug delivery systems based on carbohydrate polymers (astragalus polysaccharide, angelica polysaccharide, lycium barbarum polysaccharide, ganoderma lucidum polysaccharide, bletilla polysaccharide, glycyrrhiza polysaccharide, and epimedium polysaccharides, etc). The application of polysaccharide drug delivery systems to deliver small molecule chemotherapeutic drugs, gene drugs, and metal ion drugs was also briefly introduced. At the same time, the role of the polysaccharide drug delivery system in tumor treatment, targeted therapy, and wound healing was discussed. In addition, the research of polysaccharide delivery systems based on the therapeutic efficacy of traditional Chinese medicine was also summarized and prospected.

Metal-organic framework IRMOFs coated with a temperature-sensitive gel delivering norcantharidin to treat liver cancer.

BACKGROUND: Norcantharidin (NCTD) is suitable for the treatment of primary liver cancer, especially early and middle primary liver cancer. This compound can reduce tumors and improve immune function. However, the side effects of NCTD have limited its application. There is a marked need to reduce the side effects and increase the efficacy of NCTD. AIM: To develop a nanomaterial carrier, NCTD-loaded metal-organic framework IRMOF-3 coated with a temperature-sensitive gel (NCTD-IRMOF-3-Gel), aiming to improve the anticancer activity of NCTD and reduce the drug dose. METHODS: NCTD-IRMOF-3-Gel was obtained by a coordination reaction. The apparent characteristics and in vitro release of NCTD-IRMOF-3-Gel were investigated. Cell cytotoxicity assays, flow cytometry, and apoptosis experiments in mouse hepatoma (Hepa1-6) cells were used to determine the anti-liver cancer activity of NCTD-IRMOF-3-Gel in in vitro models. RESULTS: The particle size of NCTD-IRMOF-3-Gel was 50-100 nm, and the particle size distribution was uniform. The release curve showed that NCTD-IRMOF-3-Gel had an obvious sustained-release effect. The cytotoxicity assays showed that the free drug NCTD and NCTD-IRMOF-3-Gel treatments markedly inhibited Hepa1-6 cell proliferation, and the inhibition rate increased with increasing drug concentration. By flow cytometry, NCTD-IRMOF-3-Gel was observed to block the Hepa1-6 cell cycle in the S and G2/M phases, and the thermosensitive gel nanoparticles may inhibit cell proliferation by inducing cell cycle arrest. Apoptosis experiments showed that NCTD-IRMOF-3-Gel induced the apoptosis of Hepa1-6 cells. CONCLUSION: Our results indicated that the NCTD-IRMOF-3-Gel may be beneficial for liver cancer disease treatment.

Exposure of children and mothers to organophosphate esters: Prediction by house dust and silicone wristbands.

Ubiquitous human exposure to organophosphorus tri-esters (tri-OPEs) has been reported worldwide. Previous studies investigated the feasibility of using house dust and wristbands to assess human OPE exposure. We hypothesized that these two approaches could differ in relative effectiveness in the characterization of children and adult exposure. In the participants recruited from Guangzhou, South China, urinary levels of major OPE metabolites, including diphenyl phosphate (DPHP) and bis(butoxyethyl) phosphate (BBOEP), were significantly higher in children than their mothers (median 6.6 versus 3.7 ng/mL and 0.11 versus 0.06 ng/mL, respectively). The associations of dust or wristband-associated OPEs with urinary metabolites exhibited chemical-specific patterns, which also differed between children and mothers. Significant and marginally significant associations were determined between dust concentrations of triphenyl phosphate (TPHP), tris(2-butoxyethyl) phosphate (TBOEP), trimethylphenyl phosphate (TMPP), or tris(1-chloro-2-propyl) phosphate (TCIPP) and their metabolites in children urine and between dust tris(1,3-dichloroisopropyl) phosphate (TDCIPP), TPHP or TMPP and urinary metabolites in mothers. By contrast, wristbands exhibited better efficiency of predicting internal exposure to TDCIPP. While both house dust and wristbands exhibited the potential as a convenient approach for assessing long-term OPE exposure, their feasibility requires better investigations via larger-scale studies and standardized sampling protocols.

Emerging and legacy per- and polyfluoroalkyl substances in house dust from South China: Contamination status and human exposure assessment.

Our study investigated a large variety of per- and polyfluoroalkyl substances (PFASs) in house dust collected from Guangzhou, South China during 2015-2018. The perfluorobutane sulfonic acid (PFBS) exhibited the highest median concentration (17.6 ng/g), followed by linear perfluorooctanoic acid (L-PFOA; 4.8 ng/g), linear perfluorooctane sulfonic acid (L-PFOS; 4.2 ng/g), 6:2 fluorotelomer phosphate diester (6:2 diPAP; 3.4 ng/g), perfluorodecanoic acid (PFDA; 1.2 ng/g) and perfluoroundecanoic acid (PFUdA; 1.2 ng/g), and 6:2 chlorinated perfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA; 1.1 ng/g). Total concentrations of PFASs (median: 53 ng/g) were generally within the 25-50 percentile of the concentration range reported in global studies. However, our samples exhibited composition profiles different from those reported in many other regions. Analysis based on this and previous studies revealed that the compositions in house dust from East Asia, North America, and Europe exhibit a region-specific pattern. This may indicate region-specific market demands, application patterns, as well as associated human exposure risks. Exploration of dwelling characterizations suggested that renovation history appeared to be a significant factor influencing PFAS concentrations in house dust, although other factors may exist and play a role. Estimation of daily intakes via dust ingestion and dermal contact indicates low exposure risks from these two pathways. However, the PFAS chemical-specific biological effects, possible mixture effects, as well as additional exposure pathways, imply that the risk from indoor PFAS exposure should not be overlooked.

How to use macrophages to realise the treatment of tumour.

Macrophages (Mø) are immune cells with natural phagocytic ability and play an important role in tumorigenesis, development and metastasis. Mø play a dual role of tumour inhibition and tumour promotion in tumour development due to their two different phenotypes. Mø in the tumour microenvironment have long been referred to as tumour-associated Mø (TAMs). Mø are mainly involved in tumour resistance, cancer metastasis and mediating immunosuppression. Nowadays, Mø and Mø membranes have been widely used in drug delivery systems (DDSs) because of their good biocompatibility, natural phagocytosis and their important role in tumour development. In this review, from the perspective of Mø's role in tumour development, we present strategies and drugs of Mø targeting and focusing on the several types of biomimetic nanoparticles constructed by Mø and Mø membranes in tumour therapy, and discuss the problem of this delivery system in present research and future directions.

Hyaluronic acid-coated nanostructured lipid carriers for loading multiple traditional Chinese medicine components for liver cancer treatment.

This study aimed to develop hyaluronic acid (HA)-coated nanostructured lipid carriers (NLC) loaded simultaneously with oleanolic acid (OA), ursolic acid (UA) and Ginsenoside Rg3 (Rg3), prepared by electrostatic attraction for delivering OA, UA and Rg3 (OUR), termed HA-OUR-NLC, to tumors over expressing cluster determinant 44(CD44). The dialysis method was used to assess the in vitro release of OUR. Parameters such as pharmacokinetics, biodistribution, fluorescence in vivo endo-microscopy (FIVE), optical in vivo imaging (OIVI) data, and in vivo antitumor effects were evaluated. The results showed a total drug loading rate of 8.76±0.95% for the optimized HA-OUR-NLC; total encapsulation efficiency was 45.67±1.14%; particle size was 165.15±3.84%; polydispersity index was 0.227±0.01; zeta potential was -22.87±0.97 mV. Drug release followed the Higuchi kinetics. Pharmacokinetics and tissue distribution, as well as antitumor effects were evaluated in nude mice in vivo. HA-OUR-NLC were better tolerated, with increased antitumor activity compared with 5-Fu. In in vivo optical imaging, we use 1,1'-dioctadecyl-3,3,3',3'-tetramethy(DiR) as a fluorescent dye to label the NLC. The DiR-OUR-NLC group showed bright systemic signals, while the tumor site was weak. The present findings indicated that HA-OUR-NLC accumulated in the tumor site, prolonging OUR duration in the circulation and enhancing tumoral concentrations. Therefore, NLC prepared by electrostatic attraction constitute a good system for delivering OUR to tumors.

Isopropylated and tert-butylated triarylphosphate isomers in house dust from South China and Midwestern United States.

In the present study we determined the concentrations and compositions of a suite of isopropylated and tert-butylated triarylphosphate ester (ITP and TBPP) isomers in house dust from the city of Guangzhou located in South China and the city of Carbondale in Midwestern United States. These two groups of organophosphate esters (OPE) are structurally analogous to triphenyl phosphate (TPHP), but have rarely been investigated for environmental occurrences and human exposure risks. The majority of target ITP and TBPP isomers were 100% detected in house dust from the two locations. Median concentrations of ΣITPs (including all ITP isomers) and ΣTBPPs (including all TBPP isomers) were 63.4 ng/g (range: 16.0-500 ng/g) and 35.4 ng/g (8.1-198 ng/g) in South China house dust, respectively, compared with 476 ng/g (140-1610 ng/g) for ΣITPs and 81.3 ng/g (35.2-800 ng/g) for ΣTBPPs in Midwestern U.S. dust. The profiles of ITP or TBPP isomers were similar between the two locations and were dominated by 2-isopropylphenyl diphenyl phosphate (2IPPDPP) and 4-tert-butylphenyl diphenyl phosphate (4tBPDPP), respectively. Although the levels of ΣITPs and ΣTBPPs were generally one order of magnitude lower than those of TPHP in the same dust samples, the broad occurrences of most of these isomers in house dust from the two locations likely suggest their wide applications in household consumer products. Estimated intakes of ΣITPs and ΣTBPPs via dust ingestion were generally three orders of magnitude lower than the reference dose proposed for TPHP. However, these emerging OPE chemicals merit continuous environmental surveillance, given their possible applications as specific commercial mixtures or as components/impurities in other flame retardant/plasticizer mixtures.

Co-Existence of Organophosphate Di- and Tri-Esters in House Dust from South China and Midwestern United States: Implications for Human Exposure.

Despite numerous studies on the contamination of organophosphate triesters (tri-OPEs) in indoor environments, organophosphate diesters (di-OPEs) have rarely been investigated. The present study aimed to investigate whether di-OPEs coexist with tri-OPEs in house dust collected from Guangzhou ( n = 30), South China and the city of Carbondale ( n = 17) located in the Midwestern United States (U.S.). Median concentrations of bis(2-butoxyethyl) phosphate (BBOEP), bis(1-chloro-2-propyl) phosphate (BCIPP), bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), bis(2-ethylhexyl) phosphate (BEHP), bis(2-methylphenyl phosphate) (BMPP), and diphenyl phosphate (DPHP) were determined to be 15.9, < LOQ, 33.6, 654, 9.5, and 605 ng/g in South China house dust, and 1580, 90.6, 234, 867, 4.0, and 6500 ng/g in Midwestern U.S. dust, respectively. The total concentrations of di-OPEs (referred to ΣdiOPEs) constituted an average of 22.9% and 21.3% of the total concentrations of tri-OPEs in dust from these two locations, respectively. Median concentration ratios of DPHP and BEHP to their respective tri-OPEs (i.e., TPHP and TEHP) were determined to be 1.1 and 1.0 in South China dust and 3.7 and 1.4 in Midwestern U.S. dust, respectively, indicating possible commercial applications for these two di-OPEs. Correlative analyses reveal chemical- and region-specific relationships between di-OPEs and their respective tri-OPEs, suggesting that the relative importance of different sources (e.g., direct commercial use, impurity in tri-OPE formulas, and tri-OPE degradation) could vary for different di-OPEs. Our findings demonstrate wide occurrences of di-OPEs in an indoor environment from the studied locations and raise concerns on human exposure to dust associated di-OPEs. Future studies are needed to explore more possible di-OPEs in indoor environments and elucidate their sources, human exposure pathways, and toxicokinetics.

Multi-Dimensional Spectrum-Effect Relationship of the Impact of Chinese Herbal Formula Lichong Shengsui Yin on Ovarian Cancer.

Lichong Shengsui Yin (LCSSY) is an effective and classic compound prescription of Traditional Chinese Medicines (TCMs) used for the treatment of ovarian cancer. To investigate its pharmacodynamic basis for treating ovarian cancer, the multi-dimensional spectrum-effect relationship was determined. Four compositions (I to IV) were obtained by extracting LCSSY successively with supercritical CO2 fluid extraction, 75% ethanol reflux extraction, and the water extraction-ethanol precipitation method. Nine samples for pharmacological evaluation and fingerprint analysis were prepared by changing the content of the four compositions. The specific proportions of the four compositions were designed according to a four-factor, three-level L9(34) orthogonal test. The pharmacological evaluation included in vitro tumor inhibition experiments and the survival extension rate in tumor-bearing nude mice. The fingerprint analyzed by chromatographic condition I (high-performance liquid chromatography-photodiode array detec tor，HPLC-PDA) identified 19 common peaks. High-performance liquid chromatography-photodiode array detector-Evaporative Light-scattering Detector (HPLC-PDA-ELSD )hyphenated techniques were used to compensate for the use of a single detector, and the fingerprint analyzed by chromatographic condition II identified 28 common peaks in PDA and 23 common peaks in ELSD. Furthermore, multiple statistical analyses were utilized to calculate the relationships between the peaks and the pharmacological results. The union of the regression and the correlation analysis results were the peaks of X5, X9, X11, X12, X16, X18, Y5, Y8, Y12, Y14, Y20, Z4, Z5, Z6, and Z8. The intersection of the regression and the correlation analysis results were the peaks of X11, X12, X16, X18, Y5, Y12, and Z5. The correlated peaks were assigned by comparing the fingerprints with the negative control samples and reference standard samples, and identifying the structure using high-performance liquid chromatography-mass spectrometry detector(HPLC-MS). The results suggested that the pharmacodynamic basis of LCSSY on anti-ovarian cancer activities were germacrone, furandiene, ß-elemene, calycosin-7-glucoside, ononin, epimedin B, icariin, ginsenoside Rc, astragaloside, ginsenoside Rd, astragaloside II, and some unknown components.

Strategy for chemotherapeutic delivery using a nanosized porous metal-organic framework with a central composite design.

BACKGROUND: Enhancing drug delivery is an ongoing endeavor in pharmaceutics, especially when the efficacy of chemotherapy for cancer is concerned. In this study, we prepared and evaluated nanosized HKUST-1 (nanoHKUST-1), nanosized metal-organic drug delivery framework, loaded with 5-fluorouracil (5-FU) for potential use in cancer treatment. MATERIALS AND METHODS: NanoHKUST-1 was prepared by reacting copper (II) acetate [Cu(OAc)2] and benzene-1,3,5-tricarboxylic acid (H3BTC) with benzoic acid (C6H5COOH) at room temperature (23.7°C±2.4°C). A central composite design was used to optimize 5-FU-loaded nanoHKUST-1. Contact time, ethanol concentration, and 5-FU:material ratios were the independent variables, and the entrapment efficiency of 5-FU was the response parameter measured. Powder X-ray diffraction, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and nitrogen adsorption were used to determine the morphology of nanoHKUST-1. In addition, 5-FU release studies were conducted, and the in vitro cytotoxicity was evaluated. RESULTS: Entrapment efficiency and drug loading were 9.96% and 40.22%, respectively, while the small-angle X-ray diffraction patterns confirmed a regular porous structure. The SEM and TEM images of the nanoHKUST-1 confirmed the presence of round particles (diameter: approximately 100 nm) and regular polygon arrays of mesoporous channels of approximately 2-5 nm. The half-maximal lethal concentration (LC50) of the 5-FU-loaded nanoHKUST-1 was approximately 10 µg/mL. CONCLUSION: The results indicated that nanoHKUST-1 is a potential vector worth developing as a cancer chemotherapeutic drug delivery system.

Preparation, in vitro and in vivo evaluation of mPEG-PLGA nanoparticles co-loaded with syringopicroside and hydroxytyrosol.

This study investigated the therapeutic efficiency of monomethoxy polyethylene glycol-poly(lactic-co-glycolic acid) (mPEG-PLGA) co-loaded with syringopicroside and hydroxytyrosol as a drug with effective targeting and loading capacity as well as persistent circulation in vivo. The nanoparticles were prepared using a nanoprecipitation method with mPEG-PLGA as nano-carrier co-loaded with syringopicroside and hydroxytyrosol (SH-NPs). The parameters like in vivo pharmacokinetics, biodistribution in vivo, fluorescence in vivo endomicroscopy, and cellular uptake of SH-NPs were investigated. Results showed that the total encapsulation efficiency was 32.38 ± 2.76 %. Total drug loading was 12.01 ± 0.42 %, particle size was 91.70 ± 2.11 nm, polydispersity index was 0.22 ± 0.01, and zeta potential was -24.5 ± 1.16 mV for the optimized SH-NPs. The nanoparticle morphology was characterized using transmission electron microscopy, which indicated that the particles of SH-NPs were in uniformity within the nanosize range and of spherical core shell morphology. Drug release followed Higuchi kinetics. Compared with syringopicroside and hydroxytyrosol mixture (SH), SH-NPs produced drug concentrations that persisted for a significantly longer time in plasma following second-order kinetics. The nanoparticles moved gradually into the cell, thereby increasing the quantity. ALT, AST, and MDA levels were significantly lower on exposure to SH-NPs than in controls. SH-NPs could inhibit the proliferation of HepG2.2.15 cells and could be taken up by HepG2.2.15 cells. The results confirmed that syringopicroside and hydroxytyrosol can be loaded simultaneously into mPEG-PLGA nanoparticles. Using mPEG-PLGA as nano-carrier, sustained release, high distribution in the liver, and protective effects against hepatic injury were observed in comparison to SH.