Occurrence of 8 trace elements in Rhizoma Cibotii from China and exposure assessment.

The contamination of trace elements in Chinese edible herbs has attracted worldwide concern over the world. The objective of the present study was to investigate the occurrence and exposure assessment of eight trace elements in Rhizoma Cibotii from China. For this purpose, the method of inductively coupled plasma mass spectrometry was employed to detect the contamination levels of target trace elements in 58 Rhizoma Cibotii samples. The results demonstrated that the trace elements of Cr, Ni, Cu, Zn, and Pb were detected in all analyzed samples; the occurrence frequencies of As, Se, and Cd were 98.3%, 96.6%, and 98.3%, respectively. The highest mean levels were found in Zn (17.32 mg/kg), followed by Pb (8.50 mg/kg) and Cu (3.51 mg/kg). For a further step, one-way ANOVA was used to compare the difference of eight elements levels among groups, and Pearson's correlation analysis was used to explore the correlation between elements in Rhizoma Cibotii. A strong positive correlation between Zn and Cd was observed by Pearson's correlation analysis, which indicated that the possible presence of Cd contamination in Rhizoma Cibotii. Based on the contamination levels, the mean exposure of individual element and the health risks of eight trace elements in Rhizoma Cibotii were estimated by health risk assessment models. The calculated HQ values were less than 1, indicating that the contamination of trace elements in Rhizoma Cibotii did not pose significant health risks to human. In conclusion, the study provided baseline information on the contamination levels of trace elements in Rhizoma Cibotii. Moreover, it is necessary to monitor the trend of trace elements levels in Rhizoma Cibotii, which will be useful for ingredient control and human health protection.

Development, characterisation, and in vitro anti-tumor effect of self-microemulsifying drug delivery system containing polyphyllin I.

Polyphyllin I (PPI), an effective active ingredient in Paris polyphylla, has a diverse set of pharmacological properties. However, due to its poor solubility and oral absorption, its application and development are limited. In the study, we were committed to improving the solubility of PPI by developing a self-microemulsifying drug delivery system of PPI (PPI-SMEDDS), screening the best preparation process, and evaluating the quality and the in vivo pharmacokinetics of PPI, and PPI-SMEDDS following oral administration to rats were also studied. In addition, the pharmacological activities against human lung adenocarcinoma cell A549 in vitro were assessed. The best formulation had 15.89% ethyl oleate, 47.38% Cremophor RH40, and 36.73% 1,2 propylene glycol. The produced PPI-SMEDDS was clear and transparent, with an average particle size of 24.51 nm and a zeta potential of -17.54 ± 0.51 mV. In vitro, the cumulative release rate of PPI-SMEDDS was nearly 80% within 2 h. PPI-SMEDDS had a substantially greater area under the curve than PPI following oral treatment in rats, and the relative bioavailability of PPI in rats was 278.99%. More importantly, the anti-tumor effect of PPI-SMEDDS in vitro was significantly greater than that of PPI. These findings suggested that PPI-SMEDDS has the potential to improve the solubility, oral bioavailability of PPI, and anti-tumor effect, laying the groundwork for future research on the new PPI dosage form.

New record of Tylodelphys metacercariae (Diplostomidae) from Perccottus glenii (Odontobutidae) and their phylogenetic assessment.

Metacercariae of Tylodelphys sp. were found in the abdominal cavity of the Chinese sleeper (Perccottus glenii) collected in Liaoning Province and Inner Mongolia Autonomous Region of China. The sequences of the mitochondrial cox1 gene and ribosomal ITS1-5.8S rDNA-ITS2 region were obtained and used for molecular identification and phylogenetic assessment of this parasite species. Results of phylogenetic analyses based on ITS and cox1 markers showed that the metacercariae of Tylodelphys sp. ex P. glenii from China were conspecific with specimens of Tylodelphys sp. collected by Sokolov et al. (2013) from the same fish-host species captured earlier in West Siberia, Russia. The examined Tylodelphys sp. ex. P. glenii is the only member of the genus whose metacercariae parasitise the abdominal cavity of fish in northern Eurasia. Tylodelphys sp. ex P. glenii clustered with T. darbyi, T. immer, T. podicipina, and Tylodelphys sp. of Soldánová et al., 2017 based on mitochondrial DNA markers, and with T. darbyi, T. immer, T. kuerepus, and T. schreuringi using nuclear DNA markers.

Mechanisms of isoniazid and rifampicin-induced liver injury and the effects of natural medicinal ingredients: A review.

Isoniazid (INH) and rifampicin (RFP) are the first-line medications for tuberculosis treatment, and liver injury is the major adverse effect. Natural medicinal ingredients provide distinct benefits in alleviating patients' symptoms, lowering the liver injury risk, delaying disease progression, and strengthening the body's ability to heal. This paper summarises the recent research on the mechanisms of INH and RFP-induced liver injury and the effects of natural medicinal ingredients. It is believed that INH-induced liver injury may be attributed to oxidative stress, mitochondrial dysfunction, drug metabolic enzymes, protoporphyrin IX accumulation, endoplasmic reticulum stress, bile transport imbalance, and immune response. RFP-induced liver injury is mainly related to cholestasis, endoplasmic reticulum stress, and liver lipid accumulation. However, the combined effect of INH and RFP on liver injury risk is still uncertain. RFP can increase INH-induced hepatotoxicity by regulating the expression of drug-metabolizing enzymes and transporters. In contrast, INH can antagonize RFP-induced liver injury by reducing the total bilirubin level in the blood. Sagittaria sagittifolia polysaccharide, quercetin, gallic acid, and other natural medicinal ingredients play protective roles on INH and RFP-induced liver injury by enhancing the body's antioxidant capacity, regulating metabolism, inhibiting cell apoptosis, and reducing the inflammatory response. There are still many gaps in the literature on INH and RFP-induced liver injury mechanisms and the effects of natural medicinal ingredients. Thus, further research should be carried out from the perspectives of liver injury phenotype, injury markers, in vitro and in vivo liver injury model construction, and liver-gut axis. This paper comprehensively reviewed the literature on mechanisms involved in INH and RFP-induced liver injury and the status of developing new drugs against INH and RFP-induced liver injury. In addition, this review also highlighted the uses and advantages of natural medicinal ingredients in treating drug-induced liver injury.

Protective Effect of Hedyotis diffusa Willd. Ethanol Extract on Isoniazid-Induced Liver Injury in the Zebrafish Model.

Objective: This study aims to investigate the hepatoprotective effect and molecular mechanism of Hedyotis diffusa Willd. ethanol extract (HDWE) against isoniazid (INH)-induced liver injury in the zebrafish model. Methods: INH-induced liver injury model was established by adding an immersion bath of INH in 3 days post-fertilisation (dpf) healthy transgenic zebrafish with liver-specific fluorescence (L-FABP: EGFP). HDWE and INH were given to the zebrafish to observe liver morphology and pathology, fluorescence intensity, and the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and superoxide dismutase (SOD), as well as the content of glutathione (GSH). The chemical composition of HDWE was analysed using high-performance liquid chromatography coupled with a quadrupole-time-of flight hybrid mass spectrometer (HPLC-Q-TOF-MS). The bioactive compounds, molecular targets and signalling pathways of HDWE were predicted using network pharmacology. Subsequently, molecular docking was adopted to analyze the affinities between the bioactive components and targets by Autodock. Finally, in vitro experiments were conducted to further verify the findings. Results: Our findings showed that HDWE had a remarkable protective effect on INH-induced liver injury in zebrafish. Twenty compounds in HDWE were identified. Nineteen hub targets were identified as possible targets of HDWE, and a compound-target-pathway network was constructed. Nine bioactive compounds, ten molecular targets, and seven key signalling pathways were found to play a pivotal role in the hepatoprotective effect of HDWE against INH-induced liver injury. In vitro studies revealed that the important bioactive compound quercetin-3-O-sambubioside (QSA) could significantly reverse INH-induced cell viability decreases and had a significant effect on the associated targets predicted by network pharmacology and molecular docking. Conclusion: In this study, through the research of hepatoprotective effect of HDWE and bioinformatics analysis, the bioactive compounds, important pathways and key molecular targets were discovered. These findings could provide scientific evidence for the use of HDW in liver injury and prove to help explore its efficacy and the mechanism of action.

Isolation, purification, structural characteristics, pharmacological activities, and combined action of Hedyotis diffusa polysaccharides: A review.

Hedyotis diffusa polysaccharides, as the main component and an important bioactive substance of Hedyotis diffusa, are effective immunomodulators with various pharmacological activities, including antitumour, anti-inflammatory, antioxidant, anti-fatigue and immunity-enhancing activities. The total polysaccharides extracted from Hedyotis diffusa and Scutellaria barbata have great effects in treating liver cancer, gastric cancer, rectal cancer, glioma and nasopharyngeal carcinoma. Moreover, different materials and extraction methods result in differences in the structure and bioactivity of Hedyotis diffusa polysaccharides. Therefore, this paper summarizes the isolation, purification, structural characteristics, pharmacological activities, and combined action of Hedyotis diffusa polysaccharides to provide a reference for further study.

Polysaccharides from Hedyotis diffusa enhance the antitumor activities of cytokine-induced killer cells.

Hedyotis diffusa is a well-known traditional Chinese herbal medicine. The polysaccharides extracted from H. diffusa (HDP) exhibit a range of pharmacological activities. Transfusion of cytokine-induced killer (CIK) cell is one type of adoptive cellular immunotherapy, which is becoming an important method of cancer immunotherapy. In this present study, we investigate the immunostimulatory effect of HDP on CIK cells. CIK cells were generated by culturing and stimulating peripheral blood monocytes of healthy volunteers. They were treated with HDP at three different concentrations (10, 50, and 100 µg/mL). The effect of HDP on CIK cell populations, intracellular cytokine production, and apoptosis was examined by flow cytometry. The antitumor effect of HDP on CIK cells was determined by cytotoxicity assay. Furthermore, the effect of HDP on the antitumor activity of CIK cells in a mouse model was investigated. HDP increased the percentage of CD3+CD56+ CIK cells but did not significantly change the percentage of CD4+, CD8+, or CD4+CD25+ CIK cells. The HDP-treated CIK cells showed a greater ability to kill tumor cells, as well as higher production of interferon-γ and tumor necrosis factor-α, compared with the no-HDP-treated CIK cells. The HDP-treated CIK cells also found a lower apoptosis level in vitro. Moreover, HDP combined with CIK cells had a stronger inhibitory effect on tumor growth in the mouse model compared with the CIK or HDP treatment alone. In conclusion, the results indicated that HDP enhanced the antitumor activity of CIK cells and could be used for cancer immunotherapy combined with CIK cell therapy.

Antibacterial Meroterpenoids from the South China Sea Sponge Dysidea sp.

Chemical investigation of the sponge Dysidea sp. afforded three new sesquiterpene phenols (1-3) and one new sesquiterpene aminoquinone (4), together with four known sesquiterpene derivatives (5-8). The structures of all compounds were unambiguously elucidated by extensive spectroscopic analysis, as well as by comparison with the literature. The absolute configurations of compounds 1-4 were determined by electron capture detector (ECD) calculations and circular dichroism (CD) spectrum analysis. Their antibacterial activity against Escherichia coli (25922), Bacillus subtilis (6633), and Staphylococcus aureus (25923) were evaluated. Compounds 1 and 3 showed weak antibacterial activity against the above three strains, whereas compounds 4-8 showed potent antibacterial activities with minimum inhibitory concentration (MIC) values in the range of 3.125 to 12.5 µg/mL.

Amphiphilic block copolymers-based mixed micelles for noninvasive drug delivery.

Amphiphilic block copolymers-based mixed micelles established as new drug-loading system showed superior characteristics in delivering drug such as improved solubility, enhanced stability, multifunctional carrier materials, targeting ability, and high bioavailability. Recently, there are increasing focuses on exploration and study of noninvasive routes, and the results present perfect feasibility, improved compliance and fewer aches and pains. The aim to apply mixed micelles to noninvasive alternative routes has driven massive pharmaceutical attention. Recently, various studies of micelles strategy for noninvasive routes have been conducted to overcome the inherent barriers for uptake across the gastrointestinal tract, mucosal membranes and other in vivo noninvasive barriers, and the result argues well. The objective of this article is to summary these studies and developments of mixed micelles used on noninvasive drug delivery and provide a reference for further research.

[Chemical Constituents from Oldenlandia diffusa].

Objective: To study the chemical constituents of water extracted fraction from Oldenlandia diffusa. Methods: The compounds were isolated and purified by column chromatography on macroporous resin,silica gel,MCI gel,Sephadex LH-20,ODS medium pressure liquid chromatography and RP-semi-preparative HPLC. The structures of compounds were elucidated on the basis of physicochemical and spectral analysis. Results: 16 compounds were isolated from the water extract of Oldenlandia diffusa,and their structures were identified as asperuloside( 1),deacetyl asperuloside( 2),geniposide( 3),10-dehydrogeniposide( 4),daphylloside( 5),diffusoside A( 6),diffusoside B( 7),coniferin( 8),scandoside methyl ester( 9),acetyl scandoside methyl ester( 10),deacetylasperulosidic acid methyl ester( 11),gardenoside( 12),galioside( 13),galioside 10-acetate( 14),loliolide( 15) and( +)-neo-olivil( 16),respectively. Conclusion: Compounds 3,8 and 14 ~ 16 are obtained from Oldenlandia diffusa for the first time.

Targeted polymer-drug conjugates: Current progress and future perspective.

The combination of polymer technology and targeted drug delivery may pave the way for more effective yet safer therapeutic options for cancer therapy. Polymer-drug conjugates belonging to polymer therapeutics represent an emerging approach for drug delivery. The development of smart targeted polymer-drug conjugates that can specifically deliver drugs at a sustained rate to tumor cells may substantially improve the therapeutic index of anticancer agents. In this update, we provide an overview of the most important targeting molecules, and systemically summarize the recent advances in the development of tumor-targeted polymer-drug conjugates. Additionally, several promising approaches for the future will also be presented.

A randomized trial of somatostatin to regulate the VEGFs/VEGFRs in patients with gastric cancer.

BACKGROUND/AIMS: Angiogenesis and lymphangiogenesis are essential for tumor growth and metastasis. Vascular endothelial growth factors and their receptors (VEGFs/VEGFRs) are important to modulate vasculogenesis. Disregulation of the VEGFs/VEGFRs are closely related to tumor progression and prognosis. METHODOLOGY: We established an open-label, randomized trial to assess the effect of somatostatin on the patients with primary gastric cancer and total gastrectomy. All the 60 patients were randomly divided into somatostatin pretreatment and placebo groups and we used ELISA, real-time PCR and immunohistochemistry analysis to identify the level of VEGFs. RESULTS: The results showed that the patients pretreated with somatostatin had a significant decrease in serum VEGF level, but not in the tissue mRNA level, and the decrease in serum VEGF was partially dependent on the synthesis and degradation of the protein but not the transcription of mRNA. We also found the tissue Flt-4 (VEGFR-3) protein decreased in somatostatin pretreatment group. CONCLUSIONS: We concluded that somatostatin exerts its anti-vasculogenesis effect by downregulating the serum VEGFs and Flt-4 level. Somatostatin can be used as an important adjuvant to improve the survival of gastric cancer patients.

[Comparison of two reconstruction methods of alimentary canal after total gastrectomy].

OBJECTIVE: To evaluate the clinical value of two alimentary reconstruction methods after total gastrectomy for gastric cancer. METHODS: Thirty- one patients undergoing total gastrectomy for gastric cancer were prospectively randomly divided into two groups: single-canal jejunum interposition (n=16, group A) and P pouch with Roux-en-Y esophagojejunostomy (n=15, group B). All patients were followed up for one year. The serum nutritional parameters,body weight change and clinical effects between the two groups were compared. RESULTS: Both of the reconstruction types had the replacement of gastric function. The hemoglobin level was (102+/- 11)g/L, the total protein level (6.8+/- 3.9)g/L, and the body weight loss (1.0+/- 1.7)kg in group A, while (98+/- 12)g/L, (6.3+/- 3.0)g/L and (4.0+/- 2.3)kg in group B. There were significant differences between the two groups (all P< 0.05). CONCLUSION: The single-canal jejunum interposition reconstruction after total gastrectomy (Henley) is a better surgical method.