Azide-modified corrole phosphorus complexes for endoplasmic reticulum-targeted fluorescence bioimaging and effective cancer photodynamic therapy.

Study on corrole photosensitizers (PSs) for photodynamic therapy (PDT) has made remarkable progress. Targeted delivery of PSs is of great significance for enhancing therapeutic efficiency, decreasing the dosage, and reducing systemic toxicity during PDT. The development of PSs that can be specifically delivered to the subcellular organelle is still an attractive and challenging work. Herein, we synthesize a series of azide-modified corrole phosphorus and gallium complex PSs, in which phosphorus corrole 2-P could not only precisely target the endoplasmic reticulum (ER) with a Pearson correlation coefficient (PCC) up to 0.92 but also possesses the highest singlet oxygen quantum yields (ΦΔ = 0.75). This renders it remarkable PDT activity at a very low dosage (IC50 = 23 nM) towards HepG2 tumor cell line while ablating solid tumors in vivo with excellent biosecurity. Furthermore, 2-P exhibits intense red fluorescence (ΦF = 0.25), outstanding photostability, and a large Stokes shift (190 nm), making it a promising fluorescent probe for ER. This study provides a clinically potential photosensitizer for cancer photodynamic therapy and a promising ER fluorescent probe for bioimaging.

[Dryness-alleviating effect of processed Aurantii Fructus from Lingnan based on correlation of fecal metabolomics and dryness].

With the approach of untargeted metabolomics and correlation analysis, this study aimed to explore the mechanism of Aurantii Fructus from Lingnan region in alleviating dryness by analyzing the different effects of raw Aurantii Fructus(RAF) and processed Aurantii Fructus(PAF) on fecal endogenous metabolism in normal rats. Eighteen Sprague-Dawley(SD) rats were randomly divided into a control group(C), an RAF group(10 g·kg~(-1)), and a PAF group(10 g·kg~(-1)). After seven days of administration, the effects of RAF and PAF on dryness-related indexes were compared, including water intake, fecal water content, salivary secretion, the expression of AQP5, VIP, and 5-HT in the submandibular gland, as well as the expression of AQP3, VIP, and 5-HT in the colon. The fecal samples in each group were determined by LC-MS. Multivariate statistical analysis and Pearson correlation coefficient were used for screening the differential metabolites and metabolic pathways in alleviating dryness of RAF. The results indicated that both RAF and PAF showed certain dryness, and the dryness of RAF was more significant. Moreover, PAF could alleviate dryness of RAF to a certain extent by reducing the water intake, fecal water content, and the expression of AQP3, VIP, and 5-HT in the colon and increasing the salivary secretion and the levels of AQP5, VIP, and 5-HT in the submandibular gland. According to the analysis of fecal metabolomics, 99 and 58 metabolites related to dryness were found in RAF and PAF respectively, where 16 of them played an important role in alleviating dryness of RAF. Pathway analysis revealed that the mechanism of PAF in alleviating dryness of RAF was presumably related to the regulation of riboflavin metabolism, purine metabolism, arginine biosynthesis, pyrimidine metabolism, alanine metabolism, aspartate metabolism, glutamate metabolism, and retinol metabolism pathways. This study suggested that PAF might alleviate dryness of RAF by affecting the metabolic levels of the body, which provides a new basis for further clarifying the processing mechanism of PAF.

Hybrid Au-star@Prussian blue for high-performance towards bimodal imaging and photothermal treatment.

In recent years, branched or star-shaped Au nanostructures composed of core and protruding arms have attracted much attention due to their unique optical properties and morphology. As the clinically adapted nanoagent, prussian blue (PB) has recently gained widespread attention in cancer theranostics with potential applications in magnetic resonance (MR) imaging. In this article, we propose a hybrid star gold nanostructure（Au-star@PB）as a novel theranostic agent for T1-weighted magnetic resonance imaging (MRI)/ photoacoustic imaging（PAI） and photothermal therapy (PTT) of tumors. Importantly, the Au-star@PB nanoparticles function as effective MRI/PA contrast agents in vivo by increasing T1-weighted MR/PAI signal intensity and as effective PTT agents in vivo by decreasing the tumor volume in MCF-7 tumor bearing BALB / c mouse model as well as in vitro by lessening tumor cells growth rate. Interestingly, we found the main photothermal effect of Au-star@PB is derived from Au-star, but not PB. In summary, the hybrid structure of Au-star@PB NPs with good biological safety, significant photostability, dual imaging capability, and high therapeutic efficiency, might offer a novel avenue for the future diagnosis and treatment of cancer.

Network Pharmacology and in vitro Experimental Verification on Intervention of Quercetin, Present in Chinese Medicine Yishen Qutong Granules, on Esophageal Cancer / 中国结合医学杂志

OBJECTIVE@#To explore the potential mechanism of Yishen Qutong Granules (YSQTG) for the treatment of esophageal cancer using network pharmacology and experimental research.@*METHODS@#The effective components and molecular mechanism of YSQTG in treating esophageal cancer were expounded based on network pharmacology and molecular docking. The key compound was identified by high-performance liquid chromatography and mass spectrometry (HPLC-MS) to verify the malignant phenotype of the key compounds in the treatment of esophageal cancer. Then, the interaction proteins of key compounds were screened by pull-down assay combined with mass spectrometry. RNA-seq was used to screen the differential genes in the treatment of esophageal cancer by key compounds, and the potential mechanism of key compounds on the main therapeutic targets was verified.@*RESULTS@#Totally 76 effective compounds of YSQTG were found, as well as 309 related targets, and 102 drug and disease interaction targets. The drug-compound-target network of YSQTG was constructed, suggesting that quercetin, luteolin, wogonin, kaempferol and baicalein may be the most important compounds, while quercetin had higher degree value and degree centrality, which might be the key compound in YSQTG. The HPLC-MS results also showed the stable presence of quercetin in YSQTG. By establishing a protein interaction network, the main therapeutic targets of YSQTG in treating esophageal cancer were Jun proto-oncogene, interleukin-6, tumor necrosis factor, and RELA proto-oncogene. The results of cell function experiments in vitro showed that quercetin could inhibit proliferation, invasion, and clonal formation of esophageal carcinoma cells. Quercetin mainly affected the biological processes of esophageal cancer cells, such as proliferation, cell cycle, and cell metastasis. A total of 357 quercetin interacting proteins were screened, and 531 genes were significantly changed. Further pathway enrichment analysis showed that quercetin mainly affects the metabolic pathway, MAPK signaling pathway, and nuclear factor kappa B (NF- κ B) signaling pathway, etc. Quercetin, the key compound of YSQTG, had stronger binding activity by molecular docking. Pull-down assay confirmed that NF- κ B was a quercetin-specific interaction protein, and quercetin could significantly reduce the protein level of NF- κ B, the main therapeutic target.@*CONCLUSION@#YSQTG can be multi-component, multi-target, multi-channel treatment of esophageal cancer, it is a potential drug for the treatment of esophageal cancer.

Inhibition of PDE10A-Rescued TBI-Induced Neuroinflammation and Apoptosis through the cAMP/PKA/NLRP3 Pathway.

Phosphodiesterase 10A (PDE10A) is a dual-substrate phosphodiesterase that is highly expressed in the striatal complex. PDE10A is an important target for the treatment of ganglion dysfunction and neuroinflammation-related diseases, but its possible impact on traumatic brain injury (TBI) is still unclear. This study aims to investigate the protective effects of inhibiting PDE10A on neuroinflammation post-TBI injury and its possible molecular mechanism. The expression of PDE10A in rats and HT22 cells was determined by Western blotting. The neurological dysfunction of these rats was detected by Nissl staining, hematoxylin-eosin (HE) staining, and Morris water maze test. The activity of HT22 cells was measured by MTT. The findings of this study suggest that PDE10A is highly expressed in the brain tissue of TBI rats and HT22 cells induced by mechanical injury. Inhibition of PDE10A reduces the expression of interleukin-1ß (IL-1ß) and interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in HT22 cells induced by mechanical injury to inhibit cell apoptosis. Simultaneously, inhibition of PDE10A in TBI rats reduces the time to find a visible platform in the same pool, while cAMP/PKA activator treatment alleviates all of the abovementioned phenomena. Additionally, it is further confirmed that inhibition of PDE10A activates the cAMP/PKA pathway and downregulates the expression of NRLP3. These findings demonstrate that inhibition of PDE10A exerts neuroprotection by inhibiting apoptosis and inflammation following TBI, at least partially by the cAMP/PKA/NLRP3 pathway.

Coronary artery calcification and risk of mortality and adverse outcomes in patients with COVID-19: a Chinese multicenter retrospective cohort study.

Background: Coronary artery calcification (CAC) is an independent risk factor of major adverse cardiovascular events; however, the impact of CAC on in-hospital death and adverse clinical outcomes in patients with coronavirus disease 2019 (COVID-19) remains unclear. Objective: To explore the association between CAC and in-hospital mortality and adverse events in patients with COVID-19. Methods: This multicenter retrospective cohort study enrolled 2067 laboratory-confirmed COVID-19 patients with definitive clinical outcomes (death or discharge) admitted from 22 tertiary hospitals in China between January 3, 2020 and April 2, 2020. Demographic, clinical, laboratory results, chest CT findings, and CAC on admission were collected. The primary outcome was in-hospital death and the secondary outcome was composed of in-hospital death, admission to intensive care unit (ICU), and requiring mechanical ventilation. Multivariable Cox regression analysis and Kaplan-Meier plots were used to explore the association between CAC and in-hospital death and adverse clinical outcomes. Results: The mean age was 50 years (SD,16) and 1097 (53.1%) were male. A total of 177 patients showed high CAC level, and compared with patients with low CAC, these patients were older (mean age: 49 vs. 69 years, P < 0.001) and more likely to be male (52.0% vs. 65.0%, P = 0.001). Comorbidities, including cardiovascular disease (CVD) ([33.3%, 59/177] vs. [4.7%, 89/1890], P < 0.001), presented more often among patients with high CAC, compared with patients with low CAC. As for laboratory results, patients with high CAC had higher rates of increased D-dimer, LDH, as well as CK-MB (all P < 0.05). The mean CT severity score in high CAC group was also higher than low CAC group (12.6 vs. 11.1, P = 0.005). In multivariable Cox regression model, patients with high CAC were at a higher risk of in-hospital death (hazard ratio [HR], 1.731; 95% CI 1.010-2.971, P = 0.046) and adverse clinical outcomes (HR, 1.611; 95% CL 1.087-2.387, P = 0.018). Conclusion: High CAC is a risk factor associated with in-hospital death and adverse clinical outcomes in patients with confirmed COVID-19, which highlights the importance of calcium load testing for hospitalized COVID-19 patients and calls for attention to patients with high CAC. Supplementary Information: The online version contains supplementary material available at 10.1007/s42058-021-00072-4.

[Mechanism of Jinqi Jiangtang Tablets in treatment of pancreatic ß cell dysfunction based on network pharmacology and molecular docking technology].

The present study investigated the therapeutic efficacy and potential mechanism of Jinqi Jiangtang Tablets(JQJT) on pancreatic ß cell dysfunction based on network pharmacology and molecular docking technology. TCMSP platform was used to retrieve the chemical components and targets of the three Chinese herbal medicines of JQJT. The genes were converted to gene symbol by the UniProt, and its intersection with targets related to pancreatic ß cell function in GeneCards and CTD databases was obtained. The drugs, active components and common targets were imported into Cytoscape 3.8.2 to plot the drug-component-target network. The main effective components and targets were obtained by software analysis. The drug targets and targets related to pancreatic ß cell function were imported separately into the STRING platform for the construction of protein-protein interaction(PPI) networks. The two PPI networks were merged by Cytoscape 3.8.2 and the key targets were obtained by plug-in CytoNCA. The targets obtained from drug-component-target network and PPI networks were imported into DAVID for GO analysis and KEGG enrichment analysis. AutoDock was used to carry out molecular docking of main active components and core targets and Pymol was used to plot the molecular docking diagram. The results showed that there were 371 active components and 203 targets related to JQJT and 2 523 targets related to pancreatic ß cell damage, covering 136 common targets. The results revealed core targets(such as PTGS2, PTGS1, NOS2, ESR1 and RXRA) and effective key components(such as quercetin, kaempferol, luteolin, ß-carotene and ß-sitosterol). KEGG enrichment analysis indicated that apoptosis, inflammation, and other signaling pathways were mainly involved. Molecular docking results showed that the main active components could spontaneously bind to the targets. This study preliminarily revealed the mechanism of JQJT in improving pancreatic ß cell damage through multi-component, multi-target and multi-pathway, and provided a theoretical basis for JQJT in the treatment of pancreatic ß cell dysfunction.

Clinical Efficacy of Modified Zengyetang Against Slow Transit Constipation Due to Qi-Yin Deficiency and Its Effect on Gastrointestinal Function / 中国实验方剂学杂志

Objective:To observe the clinical effect of modified Zengyetang in treating slow transit constipation （STC） due to Qi-Yin deficiency and its effect on gastrointestinal function. Method:One hundred and thirty eligible patients were randomly divided into a control group （<italic>n</italic>=65， 6 cases dropped out or were lost to follow-up and 59 completed the trial） and a treatment group （<italic>n</italic>=65， 3 cases dropped out or were lost to follow-up and 62 completed the trial）. Patients in the control group received oral mosapride citrate dispersible tablets， 5 mg per time， three times per day， while those in the treatment group were treated with modified Zengye Tang， one bag per day， for four successive weeks. The main symptom constipation， the Patient Assessment of Constipation Symptoms （PAC-SYM）， and traditional Chinese medicine （TCM） syndrome scores， colonic transit， as well as motilin （MTL）， vasoactive intestinal peptide （VIP）， and substance P （SP） levels before and after treatment were recorded， together with the frequency of spontaneous complete bowel movements （SCBMs） per week and STC recurrence during treatment. Result:The clinical efficacy （95.16%） of the treatment group was higher than that （81.36%） of the control group （<italic>χ</italic>²=5.631 4， <italic>P</italic><0.05）， whereas the recurrence rate （30.65%） of the treatment group was significantly lower than that （57.63%） of the control group （<italic>χ</italic>²=8.941 1， <italic>P</italic><0.01）. After treatment， the main symptom constipation， three sub-scale and total PAC-SYM， and TCM syndrome scores in the treatment group were obviously decreased as compared with those in the control group （<italic>P</italic><0.01）. The proportions of residual markers at 24， 48， and 72 h in the treatment group declined in contrast to those in the control group （<italic>P</italic><0.01）. The frequency of SCBMs per week in the 2^nd， 3^rd， and 4^th weeks of the treatment group was higher than that in the control group （<italic>P</italic><0.01）. Compared with the control group after treatment， the treatment group exhibited significantly elevated MTL and SP but lowered VIP （<italic>P</italic><0.01）. Conclusion:Modified Zengyetang relieves the clinical symptoms， regulates gastrointestinal hormone secretion， increases the frequency of SCBMs， enhances colonic transit， and decreases the recurrence of patients with STC due to Qi-Yin deficiency.

PARP1 might enhance the therapeutic effect of tetrahydroxystilbene glucoside in traumatic brain injury via inhibition of Ras/JNK signalling pathway.

Trauma is the main cause of death for people aged 1-45, and among them, traumatic brain injury (TBI) is the major condition, which causes over 50,000 deaths each year and costs over 80 billion per year. Tetrahydroxystilbene glucoside (TSG) is the active ingredient of polygonum multiflorum, a traditional Chinese herbal medicine, which presented multiple pharmacological effects, including antioxidative, anti-inflammatory, reducing blood fat and neuroprotection effects. However, the effect of TSG in promoting the recovery of the nerve system after TBI is not fully understood. PARP1 is a key enzyme in repair of the damage in DNA, which is activated by binding to DNA breaks, initiating both single-strand and double-strand DNA break repair. And we thought that overexpression of TSG might enhance the effect of TSG in TBI treatment. In this study, we firstly detected the oxidative stress response related molecules in serum samples of TBI patients and a TBI mice model, and found that oxidative stress response was activated after TBI, and TSG would reduce this effect. We further noticed that inflammation related molecules presented a similar trend with oxidative stress response related molecules. These results indicated that inflammatory response and oxidative stress processes were both activated after TBI, and reduced after TSG treatment. We further detected that the apoptosis related proteins and anti-oxidative proteins were increased after TSG treatment, and these effects were enlarged after overexpression of PARP1. We further noticed that these effects might be mediated by inhibition of the Ras/JNK signalling pathway. Thus, we thought overexpression of PARP1 might enhance the therapeutic effect of TSG in TBI treatment.

Efficacy of Aeschynomene indica L. leaves for wound healing and isolation of active constituent.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine, the aerial parts of Aeschynomene indica L. (AIL) have been used for wound healing, and to treat urinary tract infection, hepatitis, enteritis, dysentery, nyctalopia, conjunctivitis, urticaria, and furuncle. However, no scientific investigation has been conducted on its wound healing potential. AIM OF THE STUDY: To investigate the effects of AIL extract on wound healing, isolate the active constituent and reveal the possible mechanism of enhancing wound healing. MATERIALS AND METHODS: The circular excision wound healing model was used to evaluate in vivo wound-healing activity. Hematoxylin and eosin staining was applied to assess inflammatory cells infiltration, angiogenesis, fibroblast proliferation, collagen synthesis, collagen remodeling, and skin appendages generation. Sirius red-picric acid staining was employed for quantitative analysis of the ratio of collagen I/III. Immunohistochemical staining for CD68, CCR7 (CD197), CD163, TGF-ß1 and α-SMA was performed to determine macrophages phenotypes transition (M1-to-M2) and prove the scar-improving effect of AIL on wound healing. RESULTS: We successfully isolated the active constituent (Sub-Fr0.2) for wound healing from AIL extract, circular excision wound healing experiment and hematoxylin & eosin staining showed Sub-Fr0.2 has a significant promoting effect on wound healing. Results of sirius red-picric acid staining demonstrated a reduced ratio of collagen I/III in the Sub-Fr0.2 group as compared with the vehicle group. Immunohistochemical staining for CD68, CCR7 (CD197), and CD163 in the Sub-Fr0.2 group exhibited an elevated speed of macrophages transiting from M1 phenotype to M2 phenotype, when compared with the vehicle group. Besides, the expression of TGF-ß1 and α-SMA were inhibited on wounds treated with the ointment containing Sub-Fr0.2. CONCLUSION: Leaves of AIL and its active constituent (Sub-Fr0.2) effectively promoted wound healing and reduced scar formation, this efficacy might be exerted by accelerating macrophages phenotypes transition and inhibiting TGF-ß1 and α-SMA expression.

New observations on the utility of CA19-9 as a biomarker in Lewis negative patients with pancreatic cancer.

BACKGROUND: Carbohydrate antigen 19-9 (CA19-9) is the best-validated biomarker for pancreatic cancer. The National Comprehensive Cancer Network (NCCN) guideline asserts that "CA19-9 will be undetectable in Lewis antigen-negative individuals". However, reports of CA19-9 secretion and its significance in Lewis (-) patients with pancreatic cancer have been inconsistent. This study was to examine serum CA19-9 levels in patients with pancreatic cancer according to Lewis status. METHODS: Patients with pancreatic cancer (1482 cases) were retrieved from a prospectively maintained database. Patients with benign pancreatic disease (210 cases) and normal subjects (315 cases) were used as controls. Lewis genotypes were examined by fucosyltransferase 3 (FUT3) sequencing. RESULTS: In patients with pancreatic cancer, 8.4% of subjects were Lewis (-), but only 41.9% of Lewis (-) subjects had CA19-9 values ≤ 2 U/mL. CA19-9 was even elevated (>37 U/mL) in 27.4% of Lewis (-) patients. The area under the receiver operating characteristic (ROC) curve for CA19-9 as a diagnostic biomarker was 0.842 in Lewis (-) patients with pancreatic cancer, which is closing to that of CA19-9 applied in all of patients with pancreatic cancer (0.898). Lewis (-) status was an independent prognostic factor for shorter survival in a multivariable analysis (hazard ratio (HR), 1.30, 95% confidence interval (CI), 1.03-1.64; P = 0.028). CONCLUSIONS: Not all Lewis (-) patients with pancreatic cancer are non-secretors of CA19-9. Contrary to general understanding, CA19-9 can retain its utility as a biomarker in these patients in spite of Lewis (-) genotype.

Hyperbaric oxygen inhibits production of CD3+ T cells in the thymus and facilitates malignant glioma cell growth.

Objective Hyperbaric oxygen (HBO) is an emerging complementary alternative medical approach in glioma treatment. However, its mode of action is unknown, so this was investigated in the present study. Methods We constructed an intracranial glioma model of congenic C57BL/6J mice. Glioma growth under HBO stimulation was assessed by bioluminescent imaging and magnetic resonance imaging. Flow cytometry assessed direct effects of HBO on reactive oxygen species (ROS) signaling of transplanted glioma cells and organs, and quantified mature T cells and subgroups in tumors, the brain, and blood. Results HBO promoted the growth of transplanted GL261-Luc glioma in the intracranial glioma mouse model. ROS signaling of glioma cells and brain cells was significantly downregulated under HBO stimulation, but thymus ROS levels were significantly upregulated. CD3+ T cells were significantly downregulated, while both Ti/Th cells (CD3+CD4+) and Ts/Tc cells (CD3+CD8+) were inhibited in tumors of the HBO group. The percentage of regulatory T cells in Ti/Th (CD3+CD4+) cells was elevated in the tumors and thymuses of the HBO group. Conclusion HBO induced ROS signaling in the thymus, inhibited CD3+ T cell generation, and facilitated malignant glioma cell growth in vivo in the intracranial glioma mouse model.

Ag-HPBs by a coating-etching strategy and their derived injectable implants for enhanced tumor photothermal treatment.

Herein, we demonstrate a coating-etching strategy to directly synthesize hollow Prussian blue (PB) nanocubes with well-dispersed Ag nanoparticles (denoted as Ag-HPB). The method is accomplished by introduction of PB precursors, K3Fe(CN)6 and Fe3+ into a reaction system containing AgNO3 and ascorbic acid, in which a series reactions contain formation of Ag nanoparticles, coating of PB on the nanoparticles, and diffusion of Ag into the PB frameworks occur. The strategy for preparation of the hollow structured Ag-HPB is intrinsically simple and does not require pre-preparation of any sacrificial templates or toxic etching agents. The obtained Ag-HPB nanocubes possess uniform size (69 nm), well-defined hollow structure, strong near-infrared photothermal conversion capacity, and excellent photoacoustic and magnetic resonance imaging abilities. Furthermore, an injectable photothermal implants are prepared for the first time by mixing the Ag-HPB nanocubes with clinically used biological glue, which significantly enhance photothermal anti-tumor efficacy, showing great potential for clinical tumor treatment.

A Multifunctional PB@mSiO2-PEG/DOX Nanoplatform for Combined Photothermal-Chemotherapy of Tumor.

In this work, we design mesoporous silica-coated Prussian blue nanocubes with PEGyltation to construct multifunctional PB@mSiO2-PEG nanocubes. The PB@mSiO2-PEG nanocubes have good biocompatibility, excellent photothermal transformation capacity, in vivo magnetic resonance and photoacoustic imaging ability. After loading antitumor drug doxorubicin (DOX) in the PB@mSiO2-PEG nanocubes, the constructured PB@mSiO2-PEG/DOX nanoplatforms show an excellent pH-responsive drug release character within 48 h, namely, an ultralow cumulative drug release amount of 3.1% at pH 7.4 and a high release amount of 46.6% at pH 5.0. Upon near-infrared laser irradiation, the PB@mSiO2-PEG/DOX nanoplatforms show an enhanced synergistic photothermal and chemical therapeutic efficacy for breast cancer than solo photothermal therapy or chemotherapy.

On-line two-dimensional countercurrent chromatography×high performance liquid chromatography system with a novel fragmentary dilution and turbulent mixing interface for preparation of coumarins from Cnidium monnieri.

This study describes a novel on-line two-dimensional countercurrent chromatography×high performance liquid chromatography (2D CCC×HPLC) system for one-step preparative isolation of coumarins from the fruits of Cnidium monnieri. An optimal biphasic solvent system composed of n-heptane/acetone/water (31:50:19, v/v) with suitable Kd values and a higher retention of the stationary phase was chosen to separate target compounds. In order to address the solvent incompatibility problem between CCC and RP-HPLC, a novel fragmentary dilution and turbulent mixing (FD-TM) interface was successfully developed. In detail, the eluent from the first dimensional CCC column was divided into fractions to form 'sample-dilution' stripes in the two switching sample loops, by the dilution water from the makeup pump. Following this, a long, thin tube was applied to mix the CCC eluent with water by in-tube turbulence, to reduce the solvent effect. Each CCC fraction was alternately trapped on the two holding columns for further preparative HPLC separation. This nationally designed FD-TM strategy effectively reduced post-column pressure and allowed a higher water dilution ratio at the post end of CCC, leading to improved sample recovery and a robust 2D CCC×HPLC isolation system. As a result, in a single 2D separation run (6.5h), eight target compounds (1-8) were isolated from 0.5g crude extract of C. monnieri, in overall yields of 1.3, 2.0, 0.5, 0.5, 0.8, 1.5, 8.2, and 15.0%, with HPLC purity of 90.1, 91.1, 94.7, 99.1, 99.2, 98.2, 97.9, and 91.9%, respectively. We anticipate that this improved 2D CCC×HPLC system, based on the novel FD-TM interface, has broad application for simultaneous isolation and purification of multiple components from other complex plant-derived natural products.

Online polar two phase countercurrent chromatography×high performance liquid chromatography for preparative isolation of polar polyphenols from tea extract in a single step.

Herein, we report an on-line two-dimensional system constructed by counter-current chromatography (CCC) coupling with preparative high-performance liquid chromatography (prep-HPLC) for the separation and purification of polar natural products. The CCC was used as the first dimensional isolation column, where an environmental friendly polar two-phase solvent system of isopropanol and 16% sodium chloride aqueous solution (1:1.2, v/v) was introduced for low toxicity and favorable resolution. In addition, by applying the stop-and-go flow technique, effluents pre-fractionated by CCC was further purified by a preparative column packed with octadecyl silane (ODS) as the second dimension. The interface between the two dimensions was comprised of a 6-port switching valve and an electronically controlled 2-position 10-port switching valve connected with two equivalent holding columns. To be highlighted here, this rationally designed interface for the purpose of smooth desalination, absorption and desorption, successfully solved the solvent compatibility problem between the two dimensional separation systems. The present integrated system was successfully applied in a one-step preparative separation and identification of 10 pure compounds from the water extracts of Tieguanyin tea (Chinese oolong tea). In short, all the results demonstrated that the on-line 2D CCC×LC method is an efficient and green approach for harvesting polar targets in a single step, which showed great promise in drug discovery.

Characterisation of water-soluble proanthocyanidins of Pyracantha fortuneana fruit and their improvement in cell bioavailable antioxidant activity of quercetin.

Proanthocyanidins (PCs) with poor bioavailability were argued for their health benefits. In this study, water-soluble polymeric polyphenolic PCs fractions from Pyracanthafortuneana fruit were used to investigate whether the presence of PCs is correlated with the increased cell antioxidant activities (CAA) of quercetin (Q). The results indicated that the most decrement in the values of EC50, which Q inhibited peroxyl radical-induced DCFH oxidation effective in the HepG2 cells, was observed to be 2.91 (vs. control 5.97) in the present of the fraction with 15.8 of the average degree of polymerisation of PCs (ADP). Also, the order of efficacy was the same with the ADP of PCs. Further, this effect is associated with the improvement of the solubility and stability of Q after the addition of the PCs. Our current study suggests that the additive effects of PCs on small molecular polyphenols may be responsible for their antioxidant benefits in vivo.

[Application of fluorescence spectra and parallel factor analysis in the classification of edible vegetable oils].

The fluorescence spectra of 22 samples of 8 kinds of edible vegetable oils (soybean oil, maize oil, olive oil, rice oil, peanut oil, walnut oil, sunflower oil and sesame oil) were measured with FS920 fluorescence spectrometer and the fluorescence matrixs (EEMs) were analyzed with parallel factor (PARAFAC) analysis model. To synthesize the capabilities of material characterization and component identification, fluorescence spectra combined with PARAFAC fulfill the classification of vegetable oils. The map feature (peak position, peak value and peak number) was obtained by analyzing three dimensional spectra and con tour maps in the range of emission wavelength from 260 to 750 nm, and excitation wavelengths from 250 to 550 nm. The fluorescent substances (unsaturated fatty acids, vitamin E and its derivatives, chlorophyll and carotenoid) corresponding to spectrum peaks were determined. The factor-number was selected and the components (vitamin E and its derivatives, linoleic acid and linolenic acid, fatty acid oxidation products, vegetable oil oxidation products) corresponding to each factor were ascertained. The four-factor excitation and emission profiles and projection score plots of PARAFAC model were plotted. Different vegetable oils can be characterized and distinguished with the map features of fluorescence spectra and sample projection plots of PARAFAC model. The results demonstrate the capability of the combination of fluorescence spectra technology and four-factor PARAFAC model for differentiating and characterizing vegetable oils.

The combination of HTATIP2 expression and microvessel density predicts converse survival of hepatocellular carcinoma with or without sorafenib.

Our previous studies have demonstrated that sorafenib can promote the dissemination of hepatocellular carcinoma (HCC) through downregulation of HTATIP2, a suppressor of tumor growth and metastasis that is associated with inhibition of angiogenesis. Here, we investigated the predictive values of the HTATIP2 level and microvessel density (MVD) with or without sorafenib administration for HCC. Three independent cohorts were included. Using tissue microarray, we assessed the relationship between HTATIP2 expression/MVD and overall survival. The results showed that high HTATIP2 expression and a low MVD value were independent protective prognostic factors after curative HCC resection (297 cases/cohort 1); however, both parameters were converted to independent negative prognostic indicators for patients with postsurgical sorafenib treatment (69/143 cases/cohort 2; P<0.05 for all). This same relationship was observed in patients that received sorafenib treatment for advanced HCC (83 cases/cohort 3; efficacy measures and survival analyses, P<0.05 for all). Moreover, the combination of HTATIP2 and MVD had better power to predict patient death and disease recurrence (P<0.001 for both). We conclude that the combination of HTATIP2 and MVD predicts the converse survival of HCC with or without sorafenib intervention. Our findings can assist in the selection of candidates for personalized treatment with sorafenib.

Antidepressant-like behavioral, anatomical, and biochemical effects of petroleum ether extract from maca (Lepidium meyenii) in mice exposed to chronic unpredictable mild stress.

Maca has been consumed as a medical food in Peru for thousands of years, and exerts anxiolytic and antidepressant effects. Our present study aimed to evaluate the behavior and anatomical and biochemical effects of petroleum ether extract from maca (ME) in the chronic unpredictable mild stress (CUMS) model of depression in mice. Three different doses of maca extract (125, 250, and 500 mg/kg) were orally administrated in the six-week CUMS procedure. Fluoxetine (10 mg/kg) was used as a positive control drug. Maca extract (250 and 500 mg/kg) significantly decreased the duration of immobility time in the tail suspension test. After treatment with maca extract (250 and 500 mg/kg), the granule cell layer in the dentate gyrus appeared thicker. Maca extract (250 and 500 mg/kg) also induced a significant reduction in corticosterone levels in mouse serum. In mouse brain tissue, after six weeks of treatment, noradrenaline and dopamine levels were increased by maca extract, and the activity of reactive oxygen species was significantly inhibited. Serotonin levels were not significantly altered. These results demonstrated that maca extract (250 and 500 mg/kg) showed antidepressant-like effects and was related to the activation of both noradrenergic and dopaminergic systems, as well as attenuation of oxidative stress in mouse brain.