Determination of the total antioxidant capacity of the Chinese tea based on a novel "peroxidase/zirconium phosphonate"composite electrochemical sensor.

In this work, a novel zirconium phosphonate (ZrPR1R2) was prepared by decorating both the aminoethoxy- group (R1) and the carboxypropyl- group (R2) on the zirconium phosphate layers in order to manipulate further the immobilization of the peroxidase (POD), and an antioxidant biosensor with higher sensitivity was constructed by dropping the POD/ZrPR1R2 composite onto the glassy carbon electrode surface. The activity of the POD/ZrPR1R2 composite was detected by Uv-vis spectra. The direct electrochemical behavior, the electrocatalytic response to dissolved oxygen and hydrogen peroxide, as well as the ability to detect total antioxidant capacity in tea sample were investigated by the methods of cyclic voltammetry. The results indicated that the immobilization of POD in ZrPR1R2 nanosheets matrix enhanced the enzymatic activity, and achieved the fast and direct electron transfer between POD and glassy carbon electrode. Moreover, the POD/ZrPR1R2 composite modified electrode show the electrocatalytic response to hydrogen peroxide in the linear range of 8.8×10-8 to 8.8×10-7 mol L-1, with the detection limit of 3.3×10-8 mol L-1. Attributing to the sensitive response to dissolved oxygen, the total antioxidant capacity can be detected directly in the real tea water by this POD/ZrPR1R2 composite modified electrode.

Exploration of the mechanisms of Callicarpa nudiflora Hook. et Arn against influenza A virus (H1N1) infection.

BACKGROUND: In our preliminary research on screening traditional Chinese medicine extracts for anti-H1N1 activity, we discovered that the 75 % ethanol extract of Callicarpa nudiflora Hook. & Arn (C. nudiflora) exhibited promising anti-H1N1 infection activity. However, the underlying active components and mechanism of action remain to be elucidated. AIM OF THE STUDY: This experiment further explores the potential active components and mechanisms of action of C. nudiflora against H1N1. METHODS: In this study, the composition of the C. nudiflora was determined using UPLC-Q-Orbitrap-MS/MS. The inhibitory effect of C. nudiflora on H1N1 was investigated using a Madin-Darby canine kidney (MDCK) cell model infected with H1N1, and the protective effect of C. nudiflora on H1N1-infected mice was examined using a Balb/c mouse model infected with H1N1. The potential mechanisms of action were demonstrated at the mRNA and protein levels. RESULTS: A total of 21 compounds were detected in C. nudiflora, which was found to act on the replication stages of H1N1. Moreover, C. nudiflora improved the survival rate of H1N1-infected mice, enhanced the organ index, alleviated the trend of weight loss, reduced lung viral load, mitigated lung tissue damage, and regulated CD4/CD8 and Th1/Th2 immune balance. Molecular mechanism studies revealed that C. nudiflora can regulate the expression of key genes in the toll-like receptor and STAT signaling pathway. CONCLUSION: C. nudiflora can inhibit H1N1 replication. It also can exert a regulatory effect on the immune response of H1N1-infected mice, and mitigate inflammatory damage by modulating the expression of key genes in the toll-like receptor and STAT signaling pathways, indicating its potential for development as an anti-H1N1 drug.

Traditional uses, chemical composition, and pharmacological effects of diaphragma juglandis fructus: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Uyghur medicine, diaphragma juglandis fructus (DJF) has been conventionally used in treating insomnia and nourishing the kidneys. According to traditional Chinese medicine, DJF can boosts kidney and astringent essence, strengthen the spleen and kidney, exert diuretic effect, clear heat, stop eructation, and treat vomiting. AIM OF THE REVIEW: Research on DJF has increased gradually in recent years, but reviews of its traditional uses, chemical composition, and pharmacological activities are scarce. The purpose of this review is to analyze the traditional uses, chemical composition, and pharmacological activities of DJF and provide an overview of the findings for further research and development of DJF resources. MATERIALS AND METHODS: Data on DJF were obtained from different databases, including Scifinder, PubMed, Web of Science, Science Direct, Springer, Wiley, ACS, CNKI, Baidu Scholar, and Google Scholar; books; and Ph.D. and MSc theses. RESULTS: According to traditional Chinese medicine, DJF has astringent properties, inhibits bleeding and banding, strengthens the spleen and kidneys, acts as a sleeping aid by reducing anxiety, and relieves dysentery due to heat exposure. The components of DJF include flavonoids, phenolic acids, quinones, steroids, lignans, and volatile oils, which exhibit good antioxidant, antitumor, antidiabetic, antibacterial, anti-inflammatory, and sedative-hypnotic properties, and present therapeutic potential for kidney diseases. CONCLUSIONS: Based on its traditional use, chemical composition, and pharmacological activities, DJF is a promising source of natural medicine in the development of functional foods, drugs, and cosmetics.

[Vitamins and Immune System Health].

Keeping the immune system healthy forms an effective way to fight infections. Past experience has shown that, in addition to effective interventions including vaccination, drug therapy, and non-pharmaceutical intervention (NPI), dietary nutrition and mental health are also key factors in maintaining immune system health and combating emerging and sudden outbreaks of infections. As the main dietary nutrients, vitamins are active regulators of the immune response and exert a critical impact on the immunity of the human body. Vitamin deficiency causes increased levels of inflammation and decreased immunity, which usually starts in the oral tissues. Appropriate vitamin supplementation can help the body optimize immune function, enhance oral immunity, and reduce the negative impact of pathogen infection on the human body, which makes it a feasible, effective, and universally applicable anti-infection solution. This review focuses on the immunomodulatory effects of vitamin A, B, C, D, and E and proposes that an omics-based new systemic approach will lead to a breakthrough of the limitations in traditional single-factor single-pathway research and provide the direction for the basic and applied research of vitamin immune regulation and anti-infection in all aspects.

Metal-dependent programmed cell death-related lncRNA prognostic signatures and natural drug sensitivity prediction for gastric cancer.

Background: Gastric cancer is one of the most important malignancies with poor prognosis. Ferroptosis and cuproptosis are newly discovered metal-dependent types of programmed cell death, which may directly affect the outcome of gastric cancer. Long noncoding RNAs (lncRNAs) can affect the prognosis of cancer with stable structures, which could be potential prognostic prediction factors for gastric cancer. Methods: Differentially expressed metal-dependent programmed cell death (PCD)-related lncRNAs were identified with DESeq2 and Pearson's correlation analysis. Through GO and KEGG analyses and GSEA , we identified the potential effects of metal-dependent PCD-related lncRNAs on prognosis. Using Cox regression analysis with the LASSO method, we constructed a 12-lncRNA prognostic signature model. Also, we evaluated the prognostic efficiency with Kaplan-Meier (K-M) survival curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) methods. The sensitivities for antitumor drugs were then predicted with the pRRophetic method. Also, we discuss Chinese patent medicines and plant extracts that could induce metal-dependent programmed cell death. Results: We constructed a metal-dependent PCD-related lncRNA-gene co-expression network. Also, a metal-dependent PCD-related gastric cancer prognostic signature model including 12 lncRNAs was constructed. The K-M survival curve revealed a poor prognosis in the high-risk group. ROC curve analysis shows that the AUC of our model is 0.766, which is better than that of other published models. Moreover, the half-maximum inhibitory concentration (IC50) for dasatinib, lapatinib, sunitinib, cytarabine, saracatinib, and vinorelbine was much lower among the high-risk group. Conclusion: Our 12 metal-dependent PCD-related lncRNA prognostic signature model may improve the OS prediction for gastric cancer. The antitumor drug sensitivity analysis results may also be helpful for individualized chemotherapy regimen design.

Liraglutide Attenuates Restenosis After Vascular Injury in Rabbits With Diabetes Via the TGF-ß/Smad3 Signaling Pathway.

Background: Lower limb ischemia due to arterial stenosis is a major complication in patients with diabetes mellitus (DM). Liraglutide is a long-acting analogue of a glucagon-like peptide 1 (GLP-1) receptor agonist used for lowering blood glucose in patients with DM, and is believed to possess cardiovascular protective effects. The aim of this study was to investigate whether liraglutide has a protective effect on blood vessels and alleviates vascular intimal hyperplasia in streptozotocin (STZ)-induced rabbits with DM and its molecular mechanism. Methods: Rabbits with DM were induced by STZ, and a lower limb ischemia model was established. The animals were divided into a control group, DM-injury group and liraglutide treatment group. Pathological staining was used to observe the intimal growth, analyze the oxidation levels of malondialdehyde (MDA), superoxide dismutase (SOD) and plasma glutathione peroxidase (GSH-Px), and analyze the changes in expression of marker proteins and signaling pathway proteins by Western blotting. A hyperglycemia (HG)-injured vascular smooth muscle cells (VSMCs) model was established to analyze reactive oxygen species (ROS) levels, Cell-Counting Kit-8 (CCK-8) was used to analyze cell proliferation, scratch assay and Transwell Migration Assay to analyze cell migration, flow cytometry to analyze apoptosis and Western blotting was used to analyze changes in the expression of marker and signaling pathway proteins. Results: The results of pathological staining showed that intimal hyperplasia was severe after diabetes-induced lower limb ischemia in rabbits at 4 weeks, and liraglutide treatment reduced symptoms. Liraglutide treatment significantly decreased MDA content, increased SOD, GSH-Px content, and augmented total antioxidant capacity levels in tissues. The results of Western blotting analysis showed that E-cadherin, mitochondrial membrane potential 9 (MMP-9), proliferating cell nuclear antigen (PCNA), and type I collagen protein expression levels were significantly decreased after liraglutide treatment compared with the DM injury group. The results indicated that liraglutide inhibited epithelial-mesenchymal transition (EMT) progression, vascular cell proliferation and migration and collagen production. Liraglutide inhibits transforming growth factor beta 1 (TGF-ß1)/Smad3 signaling pathway protein expression. In vitro assays have shown that liraglutide reduces cellular ROS levels, inhibits cell proliferation and migration and promotes apoptosis. Liraglutide down-regulated the expression of E-cadherin, MMP-9, PCNA, type I collagen protein as well as the TGF-ß1/Smad3 signaling pathway, but this effect could be reversed by tumor necrosis factor alpha (TNF-α). Conclusion: Liraglutide can significantly improve tissue antioxidant capacity, reduce vascular cell proliferation and migration via the TGF-ß1/Smad3 signaling pathway, inhibit the EMT and collagen production processes, and alleviate hyperglycemia(HG)-induced lower limb ischemia and intimal hyperplasia.

Polysaccharides derived from Chinese medicinal herbs: A promising choice of vaccine adjuvants.

Adjuvants have been used in vaccines for a long time to promote the body's immune response, reducing vaccine dosage and production costs. Although many vaccine adjuvants are developed, the use in human vaccines is limited because of either limited action or side effects. Therefore, the development of new vaccine adjuvants is required. Many studies have found that natural polysaccharides derived from Traditional Chinese medicine (TCM) possess good immune promoting effects and simultaneously improve humoral, cellular and mucosal immunity. Recently polysaccharide adjuvants have attracted much attention in vaccine preparation because of their intrinsic characteristics: immunomodulation, biocompatibility, biodegradability, low toxicity and safety. This review article systematically analysed the literature on polysaccharides possessing vaccine adjuvant activity from TCM plants, such as Astragalus polysaccharide (APS), Rehmannia glutinosa polysaccharide (RGP), Isatis indigotica root polysaccharides (IRPS), etc. and their derivatives. We believe that polysaccharide adjuvants can be used to prepare the vaccines for clinical use provided their mechanisms of action are studied in detail.

The Therapeutic Effects of Acupuncture and Electroacupuncture on Cancer-related Symptoms and Side-Effects.

In addition to cancer-related death, malignant progression also leads to a series of symptoms and side-effects, which would detrimentally affect cancer patients' the quality of life, adversely influence their adherence to treatments, and, therefore, negatively affect their long-term survival. Acupuncture and electroacupuncture (EA), as two classic treatment methods in traditional Chinese medicine, have been widely employed to cure various diseases. Recently, the clinical application of acupuncture and EA in cancer patients has received great attention. In this review, we summarized the clinical application of acupuncture and EA in alleviating the cancer symptoms, reducing the cancer treatment-related side-effects, and relieving the cancer pain. The symptoms and side-effects discussed in this review include fatigue, insomnia, chemotherapy-associated dyspepsia syndrome (CADS), pain, xerostomia, and anxiety and depression. The underlying mechanisms of the therapeutic effects of acupuncture and EA might be related to the regulation of the mitochondrial function, coordination of the activity of the nervous system, adjustment of the production of neurotransmitters, and alleviation of the immune responses. In conclusion, acupuncture and EA have been proved to be beneficial for cancer patients. More research, however, is required to clarify the potential mechanisms behind acupuncture and EA for widespread adoption in clinical application.

In situ triggering antitumor efficacy of alcohol-abuse drug disulfiram through Cu-based metal-organic framework nanoparticles.

Although approved as an alcohol-abuse drug, disulfiram (DSF) exhibited potential anticancer activity when chelated with copper (Cu). However, the low level of intrinsic Cu, toxicity originated from exogenous Cu supplementation, and poor stability of DSF in vivo severely limited its application in cancer treatment. Herein, we proposed an in situ DSF antitumor efficacy triggered system, taking advantages of Cu-based metal-organic framework (MOF). In detail, DSF was encapsulated into Cu-MOF nanoparticles (NPs) during its formation, and the obtained NPs were coated with hyaluronic acid to enhance the tumor targetability and biocompatibility. Notably, DSF loaded Cu-MOF NPs maintained stability and integrity without Cu2+ leakage in blood circulation, thus showing excellent biosafety. Once accumulating at tumor site, NPs were internalized into tumor cells via receptor-mediated endocytosis and released DSF and Cu2+ simultaneously in the hyaluronidase-enriched and acidic intracellular tumor microenvironment. This profile lead to in situ chelation reaction between DSF and Cu2+, generating toxic DSF/Cu complex against tumor cells. Both in vitro and in vivo results demonstrated the programmed degradation and recombination property of Cu-based MOF NPs, which facilitated the tumor-specific chemotherapeutic effects of DSF. This system provided a promising strategy for the application of DSF in tumor therapy.

Callicarpa nudiflora Hook. & Arn.: A comprehensive review of its phytochemistry and pharmacology.

ETHNOPHARMALOGICAL RELEVANCE: Callicarpa nudiflora Hook. & Arn. is a perennial evergreen shrub or low arbor in the Genus Callicarpa. Its dried aerial parts are used as traditional Chinese herbal medicine, Luo-hua-zi-zhu (Callicarpa nudiflora), which has been widely used in anti-bacteria and anti-ulcer in China (Commission, 2015; Development, 1994; Ming-Sheng, 2008). AIM OF THE STUDY: The present paper reviewed findings in phytochemistry and pharmacology of Callicarpa nudiflora. METHODS: Chinese and English studies on Callicarpa nudiflora were collected from databases including Web of Science, SciFinder, PubMed, Elsevier, and CNKI (Chinese), and the phytochemical and pharmacological studies of Callicarpa nudiflora were reviewed. RESULTS: A total of 300 small molecules, 173 of which are volatile oils, have been isolated from Callicarpa nudiflora. These small molecules could be divided into seven structural types - phenylpropanoids, flavonoids, triterpenes, diterpenes, iridoid glycosides, volatile oils, and other small molecules. Different types of compounds in Callicarpa nudiflora were summarized as follow: a) diterpenoid compounds can inhibit the generation of nitric oxide (NO) for exerting the function of anti-inflammation; b) triterpene compounds can play a role of anti-thrombus via inhibiting platelet aggregation and oleanane type and arbutane type pentacyclic triterpenes have the hepatoprotective activities; c) iridoid glycosides have cytotoxicity to tumor cells, and phenylpropanoids compounds have an antioxidant effect and could improve the function of memory. Our group further studied the antiviral activities of Callicarpa nudiflora finding that it has significant effects on RSV, EV71, COXB5, and HSV-1.

Chemically-Modified Curcumin 2.24: A Novel Systemic Therapy for Natural Periodontitis in Dogs.

PURPOSE: To determine the effect of a pleiotropic MMP-inhibitor, a novel chemically-modified curcumin 2.24 (CMC2.24), on the clinical and biological measures of naturally-occurring periodontitis in the beagle dog. METHODS: Eight adult female dogs with generalized periodontitis were distributed into two groups: Placebo and Treatment (n=4/group). After a 1-hr full-mouth scaling and root planing (SRP) at time 0, placebo or CMC2.24 (10mg/kg) capsules were orally administered once/day for 3 months. Various clinical periodontal parameters (e.g., pocket depth, gingival index) were measured at different time periods (0, 1, 2 and 3 months), and gingival crevicular fluid (GCF) samples and gingival tissue biopsies (3-month) were analyzed for cytokines, MMPs and cell-signaling molecules. Standardized radiographs were taken at 0 and 3-month; in addition, peripheral blood monocytes/macrophages from these dogs at 3-month were cultured and analyzed for the pro-, activated-, and total-forms of both MMP-2 and MMP-9. RESULTS: CMC2.24 treatment significantly reduced gingival inflammation (gingival index, GCF flow), pocket depth (PD), and the numbers of pockets (PD≥4mm), compared to placebo. CMC2.24 also significantly reduced MMP-9 and MMP-2 (primarily in the activated-form) in gingival tissue, alveolar bone loss, and reduced GCF IL-1ß. Cell-signaling molecules, TLR-2 (but not TLR-4) and p38 MAPK, responded to CMC2.24 in a pattern consistent with reductions in inflammation and collagenolysis. In culture, CMC2.24 had no effect on pro-MMP-9 but essentially completely blocked the conversion of pro- to activated-MMP-9 in systemic blood-derived monocytes/macrophages from these dogs. CONCLUSION: In the beagle dog model of natural periodontitis, orally administered CMC2.24 (a novel triketonic phenylaminocarbonyl-curcumin) significantly decreased clinical measures of periodontitis as well as pro-inflammatory cytokines, MMPs, and cell-signaling molecules. These and previous studies, using other in vitro and in vivo models, support the clinical potential of CMC2.24 as a novel adjunct to SRP in the treatment of chronic periodontitis.

In Situ Autophagy Disruption Generator for Cancer Theranostics.

Cancer remains a serious clinical disease awaiting new effective treatment strategies. Autophagy modulation has emerged as a novel and promising pharmacologic target critical to future drug development and anti-cancer therapy applications. Herein, we constructed an in situ autophagy disruption generator to break the balance of autophagy flow for tumor-targeting therapy. Hollow mesoporous manganese trioxide (Mn2O3) nanoparticles (NPs) were synthesized and conjugated with hyaluronic acid (HA) to form tumor-targeting drug carriers. Then, traditional autophagy inhibitor hydroxychloroquine (HCQ) was loaded into the hollow core of HA-Mn2O3, to form a multifunctional theranostics platform (HA-Mn2O3/HCQ). This nanoplatform displayed specific localization and retention in lysosomes after entering tumor cells. The synchronous release of HCQ and manganese ion (Mn2+) induced lysosomal alkalization and osmotic pressure elevation. Significantly greater lysosomal deacidification and autophagy blockade effect emerged after treatment by this nanoplatform, with in vitro tumor inhibition rate of 92.2%. Imaging experiment proved that it could selectively deliver HCQ to tumor sites and further degrade to realize simultaneous release of Mn2+ and HCQ. Micromorphological and immunofluorescence analysis demonstrated that in situ high concentrations of these two substances would achieve effective autophagy blockade. Pharmacodynamics test showed that this nanogenerator displayed the best therapeutic efficacy with 5.08-fold tumor inhibition ratio compared with the HCQ group. Moreover, the generated Mn2+ can be used as T1 contrast agent for visualizing tumor lesions and monitoring therapeutic effects. Overall, the as-made multifunctional drug-delivery system might provide a promising platform for cancer theranostics upon in situ autophagy disruption.

Phytic acid attenuates upregulation of GSK-3ß and disturbance of synaptic vesicle recycling in MPTP-induced Parkinson's disease models.

Heightened activity of glycogen synthase kinase-3ß (GSK-3ß) is linked to the degeneration of dopaminergic neurons in Parkinson's disease (PD). Phytic acid (PA), a naturally occurring compound with potent antioxidant property, has been shown to confer neuroprotection on dopaminergic neurons in PD. However, the underlying mechanism remains unclear. In the present study, MPTP and MPP+ treatments were used to model PD in mice and SH-SY5Y cells, respectively. We observed reduced tissue dopamine, disrupted synaptic vesicle recycling, and defective neurotransmitter exocytosis. Furthermore, expression of GSK-3ß was upregulated while that of ß-catenin was downregulated, concentration of cytosolic calcium was increased, and expressions of two dopamine carriers, dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2) were decreased. PA treatment attenuated the MPTP-induced upregulation of GSK-3ß, increase in cytosolic calcium concentration, decreases in the levels of DAT, VMAT2, tissue dopamine, and synaptic vesicle recycling. Importantly, disturbances in synaptic vesicle recycling are thought to be early events in PD pathology. These findings suggest that PA is a promising therapeutic agent to treat early events in PD.

The effects of five days of intensive preoperative inspiratory muscle training on postoperative complications and outcome in patients having cardiac surgery: a randomized controlled trial.

OBJECTIVE: To determine the prophylactic efficacy of short-term intensive preoperative inspiratory muscle training on the incidence of postoperative pulmonary complications in patients scheduled for cardiac surgery. DESIGN: Single-blind, randomized controlled pilot study. SETTING: TEDA International Cardiovascular Hospital, China. SUBJECTS: In total, 197 subjects aged ⩾50 years scheduled for cardiac surgery were selected. INTERVENTION: The intervention group ( n = 98) received five days of preoperative inspiratory muscle training on top of the usual care received by the patients in the control group ( n = 99). MAIN MEASURES: The primary outcome variable was the occurrence of postoperative pulmonary complications. The secondary outcome variables were inspiratory muscle strength, lung function and length of hospitalization. RESULTS: After cardiac surgery, a total of 10 (10.2%) of the 98 patients in the intervention group and 27 (27.3%) of 99 patients in the control group had postoperative pulmonary complications (risk ratio, 0.23; 95% confidence interval (CI), 0.09-0.58, P = 0.002). The study revealed that, compared with the control group, the intervention group had a significant increase in inspiratory muscle strength (by 10.48 cm H2O, P < 0.001), forced expiratory volume in the first second of expiration (FEV1) %predicted (by 3.75%, P = 0.030), forced vital capacity (FVC) %predicted (by 4.15%, P = 0.008) and maximal voluntary ventilation (MVV) %predicted (by 6.44%, P = 0.034). Length of hospital stay was 7.51 (2.83) days in the intervention group and 9.38 (3.10) days in the control group ( P = 0.039). CONCLUSION: A five-day intensive pattern of preoperative inspiratory muscle training reduced the incidence of postoperative pulmonary complications and duration of postoperative hospitalization in patients undergoing cardiac surgery.

The potential role of Annexin 3 in diapause embryo restart of Artemia sinica and in response to stress of low temperature.

Annexins are highly conserved and ubiquitous in various somatic cell types. They are involved in membrane transport and a range of calcium-regulated activities on the cell membrane surface, including vesicular transport, membrane fusion in exocytosis, signal transduction, and formation of calcium channels. They also regulate inflammatory response, cell differentiation, and interaction between cytoskeletal proteins. In this study, for the first time, an ANX3 gene from Artemia sinica ( As-anx3) was cloned. The As-anx3 full-length complementary DNA comprises 1,024 bp and has a 948 bp open reading frame encoding a 315-amino-acid polypeptide with four ANX domains. The profiles of both As-ANX3 mRNA and protein expression exhibited peaks at the 0 hr stage and had the same significant downregulation trend throughout the post-diapause embryo development stage. The ERK1/2, the phosphorylation levels of ERK1/2, and cell cycle-related protein (CDK4) expressions were analyzed by western blot analysis. The results showed that CDK4 presented a significantly ascending trend from 0 and 40 hr, although the phosphorylation levels of ERK1/2 did not increase significantly. The transcriptional and protein expressions of As-ANX3 were highly upregulated when the temperature was lowered from 25 to 15°C, but the expressions showed a gradual downward trend when the temperature was further lowered to 5°C. These results indicated that As-ANX3 plays a crucial role in restarting diapause and low-temperature stress in A. sinica.

Identification of Ellagic Acid from Plant Rhodiola rosea L. as an Anti-Ebola Virus Entry Inhibitor.

The recent 2014-2016 West African Ebola virus epidemic underscores the need for the development of novel anti-Ebola therapeutics, due to the high mortality rates of Ebola virus infections and the lack of FDA-approved vaccine or therapy that is available for the prevention and treatment. Traditional Chinese medicines (TCMs) represent a huge reservoir of bioactive chemicals and many TCMs have been shown to have antiviral activities. 373 extracts from 128 TCMs were evaluated using a high throughput assay to screen for inhibitors of Ebola virus cell entry. Extract of Rhodiola rosea displayed specific and potent inhibition against cell entry of both Ebola virus and Marburg virus. In addition, twenty commercial compounds that were isolated from Rhodiola rosea were evaluated using the pseudotyped Ebola virus entry assay, and it was found that ellagic acid and gallic acid, which are two structurally related compounds, are the most effective ones. The activity of the extract and the two pure compounds were validated using infectious Ebola virus. The time-of-addition experiments suggest that, mechanistically, the Rhodiola rosea extract and the effective compounds act at an early step in the infection cycle following initial cell attachment, but prior to viral/cell membrane fusion. Our findings provide evidence that Rhodiola rosea has potent anti-filovirus properties that may be developed as a novel anti-Ebola treatment.

NIR light-induced tumor phototherapy using photo-stable ICG delivery system based on inorganic hybrid.

NIR responsive inorganic hybrid (Ti@GO) was synthesized. It could absorb NIR light and convert it into local hyperthermia and ROS synchronously. Ti@GO was firstly developed as a photosensitizer and a photothermal agent to realize tumor PTT and PDT. For anti-tumor application, HA was grafted on Ti@GO simultaneously as water solubility improver and tumor targeting moiety. ICG was chosen as a model drug. Results demonstrated that HA-Ti@GO could remarkably improve ICG stability and drug accumulation in 4T1 cells, enhance tumor phototherapy efficiency and reduce light-associated side effects. HA-Ti@GO/ICG under NIR laser irradiation showed a significant decreased cell viability of 20.7±2.6% and a high DNA damage degree of 82.4±8.3%. Moreover, in vivo results showed that HA-Ti@GO/ICG plus NIR laser achieved almost complete tumor regression on 4T1 tumor-bearing mice, with a tumor volume of 67.0 mm3. Taken together, our study provided a promising strategy to realize synergistic PTT/PDT tumor therapy with a single NIR light.

An intelligent NIR-responsive chelate copper-based anticancer nanoplatform for synergistic tumor targeted chemo-phototherapy.

The chelate copper-based anticancer drug bleomycin (BLM) is usually believed to bind metal ions especially Cu(ii) to generate the "activated BLM" for DNA cleavage. Herein, BLM and L-menthol (LM) co-loaded hollow mesoporous Cu2-xS nanoparticles (HMCu2-xS NPs) with surface folic acid (FA) modification were formulated to construct an intelligent NIR-responsive nanoplatform for synergistic tumor targeted chemo-phototherapy. With the tumor targeting ability of the folate receptor (FR)-positive, FA-HMCu2-xS/BLM/LM could pinpoint tumor cells efficiently. Under NIR irradiation, the versatile HMCu2-xS would be bound to exploit the merits of phototherapy (including PTT and PDT-like effects) for cancer treatment. Meanwhile, benefiting from the controllable "solid-liquid" (S-L) phase transition feature of LM as a gatekeeper, FA-HMCu2-xS/BLM/LM offered a platform for simultaneous NIR-mediated temperature-responsive BLM and copper ion release, which further initiated the generation of the "activated BLM". As a matter of course, the remarkable synergistic combination of Cu-dependent chemo-phototherapy in vitro and in vivo by such a smart all-in-one drug delivery nanoplatform developed here provided information for advancing nanotherapy in biomedical fields.

[Inhibitory effect of Glehniae Radix petroleum ether part on TGF-ß1-induced epithelial mesenchymal transition in A549 cells].

To study the inhibitory effect of Glehniae Radix petroleum ether part on TGF-ß1-induced epithelial mesenchymal transition in non-small cell lung cancer A549 and its possible mechanism. With type Ⅱ epithelial cells of lung cancer A549 as the research object, the experiment was performed in 5 µg•L⁻¹ TGF-ß1-induced epithelial mesenchymal transition model,and blank control group, model group and Glehniae Radix petroleum ether group were set up. MTT assay was carried out to detect the effect of petroleum ether extract of Glehniae Radix on the survival of A549 cells. A549 cells induced by TGF-ß1(5 µg•L⁻¹) was intervened by different polar parts of Glehniae Radix, Real-time quantitative polymerase chain reaction(RT-qPCR) was used to analyze mRNA expressions of the epithelial mesenchymal transition markers, such as ColⅠ,E-cadherin,Vimentin and α-SMA. Enzyme linked immunosorbent assay(ELISA) was used to detect hydroxyproline(HYP) level. The migration and invasion abilities of cells were detected through wound scratch assay. According to the experimental results, the petroleum ether extract of Glehniae Radix could inhibit the growth of A549 cells in a concentration-dependent manner. Compared with model group, Glehniae Radix petroleum ether part group could effectively inhibit mRNA expressions of ColⅠ,Vimentin and α-SMA, but improve expression of E-cadherin.Glehniae Radix petroleum ether part could reduce the content of hydroxyproline in cells and inhibit the migration of A549 cells.Therefore, the petroleum ether extract of Glehniae Radix can effectively inhibit the occurrence of epithelial mesenchymal transition induced by TGF-ß1 induced alveolar epithelial cells, and Glehniae Radix petroleum ether part may be a potential drug for idiopathic pulmonary fibrosis. The mechanism may be achieved through the regulation of ColⅠ, Vimentin, α-SMA and E-cadherin.

Copper sulfide nanoparticle-based localized drug delivery system as an effective cancer synergistic treatment and theranostic platform.

Localized cancer treatment with combination therapy has attracted increasing attention for effective inhibition of tumor growth. In this work, we introduced diffusion molecular retention (DMR) tumor targeting effect, a new strategy that employed transferrin (Tf) modified hollow mesoporous CuS nanoparticles (HMCuS NPs) to undergo extensive diffuse through the interstitium and tumor retention after a peritumoral (PT) injection. Herein, HMCuS NPs with strong near-infrared (NIR) absorption and photothermal conversion efficiency could serve as not only a drug carrier but also a powerful contrast agent for photoacoustic imaging to guide chemo-phototherapy. The iron-dependent artesunate (AS), which possessed profound cytotoxicity against tumor cell, was used as model drug. As a result, this AS loaded Tf-HMCuS NPs (AS/Tf-HMCuS NPs) system could specially target to tumor cells and synchronously deliver AS as well as irons into tumor to achieve enhanced antitumor activity. It was found that AS/Tf-HMCuS NPs was taken up by MCF-7 cells via Tf-mediated endocytosis, and could effectively convert NIR light into heat for photothermal therapy as well as generated high levels of reactive oxygen species (ROS) for photodynamic therapy. In addition, in vivo antitumor efficacy studies showed that tumor-bearing mice treated with AS/Tf-HMCuS NPs through peritumoral (PT) injection under NIR laser irradiation displayed the strongest inhibition rate of about 74.8%, even with the reduced frequency of administration. Furthermore, to demonstrate DMR, the optical imaging, photoacoustic tomography and immunofluorescence after PT injection were adopted to track the behavior of AS/Tf-HMCuS NPs in vivo. The results exhibited that Tf-HMCuS NPs prolonged the local accumulation and retention together with slow vascular uptake and extensive interstitial diffusion, which was consistent with the biodistribution studies of AS/Tf-HMCuS NPs. Therefore, the approach of localized delivery through DMR combined with multi-mechanism therapy may be a promising method for cancer treatment. STATEMENT OF SIGNIFICANCE: In recent years, localized cancer treatment using different biomaterials has attracted increasing attention for effective inhibition of tumor growth. However, it is still challenging for this kind of system to achieve a high drug loading, overcome biological barriers from the site of injection to the site of action, and combine synergetic therapy with diagnosis without adversely affecting the formation process. This study provides a localized diffusion molecular retention (DMR) tumor targeting drug delivery system based on hollow mesoporous copper sulfide nanoparticles (HMCuS NPs) entrapment of anticancer drug for the first time, which can achieve high drug loading, improve local drug accumulation and retention, accomplish synergistic combination of chemo-phototherapy, and finally enhance antitumor effect. In addition, HMCuS NPs also possesses the property suitable for photoacoustic imaging, which could offer us a theranostic platform.