Enzyme-mimic catalytic activities and biomedical applications of noble metal nanoclusters.

Noble metal (e.g., Au and Ag) nanoclusters (NCs), which exhibit structural complexity and hierarchy comparable to those of natural proteins, have been increasingly pursued in artificial enzyme research. The protein-like structure of metal NCs not only ensures enzyme-mimic catalytic activity, including peroxidase-, catalase-, and superoxide dismutase-mimic activities, but also affords an unprecedented opportunity to correlate the catalytic performance with the cluster structure at the molecular or atomic levels. In this review, we aim to summarize the recent progress in programming and demystify the enzyme-mimic catalytic activity of metal NCs, presenting the state-of-the-art understandings of the structure-property relationship of metal NC-based artificial enzymes. By leveraging on a concise anatomy of the hierarchical structure of noble metal NCs, we manage to unravel the structural origin of the catalytic performance of metal NCs. Noteworthily, it has been proven that the surface ligands and metal-ligand interface of metal NCs are instrumental in influencing enzyme-mimic catalytic activities. In addition to the structure-property correlation, we also discuss the synthetic methodologies feasible to tailoring the cluster structure at the atomic level. Prior to the closure of this review with our perspectives in noble metal NC-based artificial enzymes, we also exemplify the biomedical applications based on the enzyme-mimic catalysis of metal NCs with the theranostics of kidney injury, brain inflammation, and tumors. The fundamental and methodological advancements delineated in this review would be conducive to further development of metal NCs as an alternative family of artificial enzymes.

Engineering Au44 Nanoclusters for NIR-II Luminescence Imaging-Guided Photoactivatable Cancer Immunotherapy.

Immunotherapy is an advanced therapeutic strategy of cancer treatment but suffers from the issues of off-target adverse effects, lack of real-time monitoring techniques, and unsustainable response. Herein, an ultrasmall Au nanocluster (NC)-based theranostic probe is designed for second near-infrared window (NIR-II) photoluminescence (PL) imaging-guided phototherapies and photoactivatable cancer immunotherapy. The probe (Au44MBA26-NLG for short) is composed of atomically precise and NIR-II emitting Au44MBA26 NCs (here MBA denotes water-soluble 4-mercaptobenzoic acid) conjugated with immune checkpoint inhibitor 1-cyclohexyl-2-(5H-imidazo[5,1-a]isoindol-5-yl)ethanol (NLG919) via a singlet oxygen (1O2)-cleavable linker. Upon NIR photoirradiation, the Au44MBA26-NLG not only enables NIR-II PL imaging of tumors in deep tissues for guiding tumor therapy but also allows the leverage of photothermal property for cancer photothermal therapy (PTT) and the photogenerated 1O2 for photodynamic therapy (PDT) and releasing NLG919 for cancer immunotherapy. Such a multiple effect modulated by Au44MBA26-NLG prompts the proliferation and activation of effector T cells, upshifts systemic antitumor T-lymphocyte (T cell) immunity, and finally suppresses the growth of both primary and distant tumors in living mice. Overall, this study may provide a promising theranostic nanoplatform toward NIR-II PL imaging-guided phototherapies and photoactivatable cancer immunotherapy.

Use of surfactant-based amorphous solid dispersions for BDDCS class II drugs to enhance oral bioavailability: A case report of resveratrol.

This paper aimed to improve in vitro dissolution/solubility as well as inhibit intestinal metabolism and thus enhance oral bioavailability for a BDDCS class II drug by constructing surfactant-based amorphous solid dispersions using resveratrol (RES) as a model drug. After preliminary screening of polymers and surfactants, and subsequent prescription optimization, two optimized spray-drying RES-polymer-surfactant ASDs were obtained and exhibited a significant increase in solubility of RES by 2.69-3.45-fold compared to crystalline RES, and by 1.13-1.56-fold compared to corresponding RES-polymer ASDs, maintaining a higher concentration in the dissolution process. A metabolism study using everted sacs showed that two optimized ASDs reduced the concentration ratio of RES-G to RES to 51.66%-52.05% of crystalline RES on the serosal side of the rat everted intestinal sac at 2 h. Consequently, these two RES-polymer-surfactant ASDs achieved significantly higher exposure of RES in the plasma with significant enhancements in Cmax (2.33-2.35-fold higher than crystalline RES, and 1.72-2.04-fold higher than corresponding RES-polymer ASDs), and in AUC 0-∞ (3.51-3.56-fold higher than crystalline RES, and 1.38-1.41-fold higher than corresponding RES-polymer ASDs). These advantages of the RES-polymer-surfactant ASDs in oral absorption of RES were attributed to solubilization by ASDs and metabolic inhibition by UGT inhibitors. The introduction of surfactants including EL and Lab to ASDs plays an important role in inhibiting glucuronidation and further improving solubility. This study demonstrated that such surfactant-based amorphous solid dispersions may serve as a new approach to increase the oral absorption of BDDCS class II drugs.

Ligand engineering of Au44 nanoclusters for NIR-II luminescent and photoacoustic imaging-guided cancer photothermal therapy.

Developing a high-performance noninvasive probe for precise cancer theranostics is very challenging but urgently required. Herein, a novel Au nanoclusters (NCs)-based probe was designed for cancer theranostics via ligand engineering by conjugating photoluminescent (PL) Au44 NCs in the second near-infrared window (NIR-II, 1000-1700 nm) with aromatic photoacoustic (PA)/photothermal molecules through click chemistry. This design bypasses the incompatibility dilemma between photoluminescence (PL) attributes and PA/photothermal properties because the rigidity of the PA/photothermal molecules can lead to aggregation-induced emission (AIE) of the Au(i)-ligand shell of the Au NCs by constraining their nonradiative relaxation. Benefiting from strong NIR-II PL with emissions at 1080 and 1240 nm, high photothermal conversion efficiency (65.12%), low cytotoxicity, appropriate renal clearance, and enhanced permeability and retention (EPR) effect, the as-designed Au NC-based theranostic probe achieves ultradeep NIR-II PL/PA imaging-guided cancer photothermal therapy (PTT). Remarkably, 16 days after photothermal treatment guided by NIR-II PL/PA imaging, mice were all healed without tumor recurrence, while the average life span of the mice in the control groups was only 17-21 days. This study is interesting because it provides a paradigm for designing a metal NC-based theranostics probe, and it may add fundamentally and methodologically to noninvasive imaging-guided disease therapy.

Cu(I) complexes with aggregation-induced emission for enhanced photodynamic antibacterial application.

This communication reports the design of aggregation-induced emission (AIE)-featured PEG-condensed Cu(I)-p-MBA aggregates (PCuA). Benefiting from the AIE trait and intrinsic antibacterial property of Cu species, the as-developed PCuA exhibits enhanced photodynamic antibacterial activities against broad-spectrum bacteria, providing a paradigm in the design of novel antibacterial agents.

The effectiveness of a mHealth-based integrated hospital-community-home program for people with type 2 diabetes in transitional care: a protocol for a multicenter pragmatic randomized controlled trial.

BACKGROUND: Diabetes is a progressive condition requiring long-term medical care and self-management. The ineffective transition from hospital to community or home health care may result in poor glycemic control and increase the risk of serious diabetes-related complications. In China, the most common transitional care model is home visits or telephone interventions led by a single healthcare setting, with a lack of cooperation between specialists and primary care, which leads to inadequate service and discontinuous care. Thus, an integrated hospital-community-home (i-HCH) transitional care program was developed to promote hospital and community cooperation and provide comprehensive and continuous medical care for type 2 diabetes mellitus (T2DM) via mobile health (mHealth) technology. METHODS: This protocol is for a multicenter randomized controlled trial in T2DM patients. Hospitalized patients diagnosed with T2DM who meet the eligibility criteria will be recruited. The patients will be randomly allocated to either the intervention or the control group and receive the i-HCH transitional care or usual transitional care intervention. The change in glycated hemoglobin is the primary outcome. Secondary outcome measures are blood pressure, lipids (total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein), body mass index, self-management skills, quality of life, diabetes knowledge, transitional care satisfaction and the rate of readmission. The follow-up period of this study is six months. DISCUSSION: The study will enhance the cooperation between local hospitals and communities for diabetes transitional care. Research on the effectiveness of diabetes outcomes will have potentially significant implications for chronic disease patients, family members, health caregivers and policymakers. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900023861: June 15, 2019.

Effect of Baicalein on the Pharmacokinetics of Cilostazol and Its Two Metabolites in Rat Plasma Using UPLC-MS/MS Method.

This study aimed to explore the effect of baicalein on the pharmacokinetics of cilostazol (CLZ) and its two metabolites 3,4-dehydro cilostazol (3,4-CLZ) and 4'-trans-hydroxy cilostazol (4'-CLZ) in rats using a newly established ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. Ticagrelor was used as an internal standard (IS), then cilostazol and its two metabolites were separated by means of a UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 µm) using gradient elution method with 0.4 ml/min of flow rate. Acetonitrile as organic phase and water with 0.1% formic acid as aqueous phase constructed the mobile phase. Selective reaction monitoring (SRM) mode and positive ion mode were preferentially chosen to detect the analytes. Twelve SD rats were divided into two groups (n = 6) when CLZ was administered orally (10 mg/kg) with or without oral baicalein (80 mg/kg). The selectivity, linearity, recovery, accuracy, precision, matrix effect and stability of UPLC-MS/MS assay were satisfied with the standards of United States Food and Drug Administration guidelines. In control group, AUC0-∞ and Cmax of CLZ were 2,169.5 ± 363.1 ng/ml*h and 258.9 ± 82.6 ng/ml, respectively. The corresponding results were 3,767.6 ± 1,049.8 ng/ml*h and 308.6 ± 87.9 ng/ml for 3, 4-CLZ, 728.8 ± 189.9 ng/ml*h and 100.3 ± 51.3 ng/ml for 4'-CLZ, respectively. After combination with baicalein, AUC0-∞ and Cmax of CLZ were 1.48, 1.38 times higher than the controls. Additionally, AUC0-∞ and Cmax were separately decreased by 36.12 and 19.54% for 3,4-CLZ, 13.11 and 44.37% for 4'-CLZ. Baicalein obviously alters the pharmacokinetic parameters of CLZ, 3,4-CLZ and 4'-CLZ in rats. These results suggested that there was a potential drug-drug interaction between baicalein and CLZ. Therefore, it must raise the awareness when concomitant use of CLZ with baicalein, the dosage regimen of CLZ should be taken into consideration, if this result is confirmed in clinical studies.

Simulation of emergency evacuation from construction site of prefabricated buildings.

To ensure the safe construction of prefabricated buildings and improve the efficiency of the safe evacuation of construction personnel after a fire caused by improper operation during construction, this study used the PyroSim software to numerically simulate a fire situation based on the size and volume of a prefabricated building construction site. The variation rules of smoke visibility, CO concentration, and ambient temperature in the construction site of prefabricated buildings were analyzed and the available safe evacuation time was determined. Moreover, the Pathfinder software was used for simulation in combination with the physical attributes of personnel, evacuation speed, and personnel proportions. The time required for safe evacuation was determined and the factors influencing the evacuation time, such as the quantity and location of stacked prefabricated components, machinery, and appliances, and the number of on-site construction personnel, were analyzed. The data collected by the temperature sensor, CO concentration sensor, and visibility sensor reveal that the visibility and crash time are the key factors restricting the efficiency of personnel avoidance and evacuation. At 400 s, the visibility at the escape exit of the prefabricated apartment construction site was lower than 5 m. The crashing time of the building was 360 s, which is the critical point for casualties. The first emergency evacuation simulation took 398.7 s. The required safe evacuation time (TREST) > available safe evacuation time (TASET), and the original site layout cannot facilitate the safe evacuation of all construction workers. The evacuation time can be effectively reduced by re-planning the stacking positions of prefabricated construction site components, construction equipment, and other items, and reducing the number of personnel in the construction plane. The results of the second simulation reveal that the safe evacuation time (TREST) is 355.2 s. Because it is required that the safety evacuation time (TREST) < available safe evacuation time (TASET), the results are in line with the emergency evacuation requirements. The findings of this study can provide a theoretical basis for the rational planning of evacuation passages at the construction sites of prefabricated buildings and assist the management of construction site safety.

Adjunct therapy with probiotics for chronic urticaria in children: randomised placebo-controlled trial.

BACKGROUNDS: Chronic urticaria is a common disorder of the skin, characterised by recurrent skin wheals and angioedema. Recent reports have shown that altered diversity and composition of the gut microbiota may lead to imbalances in immune regulation, a causal factor in the occurrence of chronic urticaria. OBJECTIVE: This study aimed to evaluate the efficacy of the Yimingjia® probiotic formula in the adjuvant treatment of chronic urticaria in children. METHODS: We enrolled 206 children with confirmed diagnoses of chronic urticaria and randomly assigned them to the treatment (n = 104) or placebo group (n = 102). The children in each group were treated with desloratadine dry suspension, and those in the treatment group also received Yimingjia®. Clinical efficacy was evaluated at 1, 2 and 4 weeks. RESULTS: Clinical symptom scores did not differ significantly at weeks 1 and 2 (p > 0.05), but at 4 weeks, wheal size and attack frequency were significantly reduced in the treatment group (p = 0.049 and 0.03, respectively). The overall response rate (significant improvement + complete response) significantly differed between the treatment (80.8%) and placebo groups (62.5%) (χ2 = 4.20, p = 0.04). CONCLUSION: Adjunct therapy with Yimingjia® was safe and effective at 4 weeks in the treatment of chronic urticaria in children. The study was registered under trial number NCT03328897.

A flexible polyelectrolyte-based gel polymer electrolyte for high-performance all-solid-state supercapacitor application.

A simple polymerization process assisted with UV light for preparing a novel flexible polyelectrolyte-based gel polymer electrolyte (PGPE) is reported. Due to the existence of charged groups in the polyelectrolyte matrix, the PGPE exhibits favorable mechanical strength and excellent ionic conductivity (66.8 mS cm-1 at 25 °C). In addition, the all-solid-state supercapacitor fabricated with a PGPE membrane and activated carbon electrodes shows outstanding electrochemical performance. The specific capacitance of the PGPE supercapacitor is 64.92 F g-1 at 1 A g-1, and the device shows a maximum energy density of 13.26 W h kg-1 and a maximum power density of 2.26 kW kg-1. After 10 000 cycles at a current density of 2 A g-1, the all-solid-state supercapacitor with PGPE reveals a capacitance retention of 94.63%. Furthermore, the specific capacitance and charge-discharge behaviors of the flexible PGPE device hardly change with the bending states.

An empirical study on energy utilization efficiency, economic development, and sustainable management.

Based on the premise of sustainable development of the environment, how to achieve the balance of energy utilization, economic development, and sustainable management of the environment is becoming increasingly important in the process of stable economic development. This paper analyzes the concept of environmental Kuznets curve, taking 35 European countries as the research objects, first discusses the trend of energy utilization efficiency from 1990 to 2013, and then analyzes the relationship between energy efficiency and economic development. Empirical results show that labor has a significant negative impact on energy efficiency and the increase in labor input will reduce energy efficiency. If the added value of national manufacturing accounts for a higher percentage in GDP, it will have a negative impact on the effectiveness of energy utilization. In addition, when the national price level is high, price fluctuation will increase the price of energy utilization, or the cost of energy input in economic activities, which will further reduce the country's energy efficiency performance. Lastly, the empirical study also found that energy efficiency and economic development showed a quadratic U-shaped relationship, indicating that the long-term energy efficiency of the country will first decline and then rise during economic activities.

Downregulation of CD44v6 Enhances Chemosensitivity by Promoting Apoptosis and Inhibiting Autophagy in Colorectal Cancer HT29 Cells.

BACKGROUND: Chemotherapy resistance reduces the effectiveness of chemotherapeutic drugs greatly, resulting in treatment failure. Therefore, exploring chemoresistance-related genes and the corresponding mechanism is extremely important. The central role of CD44v6 in colorectal cancer has been previously reported. However, the effects of CD44v6 gene knockdown on the chemosensitivity of colorectal cancer cells are not conclusive. MATERIAL AND METHODS: A stable CD44v6 knockdown cell model in HT29 cells (HT29-KD) was established via lentiviral transduction. A quantitative real-time polymerase chain reaction (PCR) was carried out to confirm the knockdown efficiency. The chemosensitivity of cells to 5-fluorouracil (5-FU) was determined by a cell counting kit (CCK)-8 assay. Cell apoptosis and the cell cycle were assessed by flow cytometry. RESULTS: The CD44v6 knockdown cell model was successfully constructed by using lentiviral transduction. Upon treatment with 5-FU, the inhibitory rate for cell activity of HT29-KD cells was significantly higher than that of the control group (HT29-NC). CD44v6 gene knockdown did not significantly affect HT-29 cell proliferation, according to the CCK-8 assay and cell cycle analysis. The cell apoptosis assay revealed that CD44v6 gene knockdown promoted HT-29 cell apoptosis. Without 5-FU treatment, there was no significant difference in terms of the relative expression level of the autophagy-related gene BECN1 between the two groups. However, with 5-FU treatment, the relative expression level of BECN1 in HT29-KD cells was much lower than that in HT29-NC cells. CONCLUSION: Our study confirms that CD44v6 gene knockdown can enhance chemosensitivity in HT29 cells by promoting apoptosis and inhibiting autophagy, thus affirming the effects of CD44v6 on the chemosensitivity of colorectal cancer.

Effects of continuous care for patients with type 2 diabetes using mobile health application: A randomised controlled trial.

BACKGROUND: Type 2 diabetes is a worldwide disorder that affects millions of people and can exert negative clinical and social effects on the patients. In some previous studies, mobile health applications have been used as a means of clinical intervention. However, the therapeutic effect of continuous care through mobile phone applications for patients with type 2 diabetes remains unclear. OBJECTIVE: This study aimed to explore the clinical effect of continuous care for patients with type 2 diabetes using mobile health application by comparing traditional discharge nursing. METHODS: In total, 120 patients with type 2 diabetes were randomly divided into two groups: The test group received continuous care based on the mobile phone application (n = 60), and the control group received conventional care (n = 60). Primary clinical outcomes, such as Glycaemic Haemoglobin (GH) levels, blood glucose levels, self-care abilities, disease cognition abilities, and the number of readmissions, were examined in both groups. RESULTS: The results showed significant improvements pertaining to disease awareness levels (81.28 vs 71.34, P < .05), self-management abilities (9.14 vs 7.81, P < .05), GH (-1.50% vs -0.76%, P < .05), fast blood glucose (-3.23 vs -1.25 mmol/L, P < .05), postprandial blood glucose levels (-4.34 vs -2.34 mmol, P < .05), and control levels in the test group. Moreover, in the test group, the frequency of rehospitalisation was reduced during the intervention period, as was the average number of rehospitalisation within 6 months after discharge (-1.19 vs P < .05). CONCLUSIONS: Continuous care based on a mobile health application has potential as a management strategy for patients with type 2 diabetes.

Inhibition on acid-sensing ion channels and analgesic activities of flavonoids isolated from dragon's blood resin.

Acid-sensing ion channel (ASIC) serves important roles in the transmission of nociceptive information. To confirm the analgesic mechanism of dragon's blood resin, patch-clamp technique, in vivo animal experiments, and immunohistochemical staining were used to observe the effects of the three flavonoids (loureirin B, cochinchinemin A, and cochinchinemin B) isolated from dragon's blood resin on ASIC. Results showed that the three flavonoids exerted various inhibitory effects on ASIC currents in rat dorsal root ganglion (DRG) neurons. The combination of the three flavonoids with total concentration of 6.5 µM could decrease (53.8 ± 4.3%) of the peak amplitude and (45.8 ± 4.5%) of the sustained portion of ASIC currents. The combination of the three flavonoids was fully efficacious on complete Freud's adjuvant (CFA)-induced inflammatory thermal hyperalgesia at a dose of 6.5 mM similar with amiloride at 10 mM. The analgesic effects of the combination could be weakened by an ASIC activator 2-guanidine-4-methylquinazoline. CFA-induced hyperalgesia was accompanied by c-Fos up-regulation in DRG neurons, and the combination rescued thermal hyperalgesia through down-regulation of c-Fos and ASIC3 expression in CFA-induced inflammation. These collective results suggested that the flavonoids isolated from dragon's blood resin could be considered as the chemical compounds that exert analgesic effects on inflammatory thermal pain due to action on ASIC.

Environmental Tax Reform and the "Double Dividend" Hypothesis in a Small Open Economy.

In this paper, we build and analyze a general equilibrium model to evaluate the effects of environment tax reform on a small open economy in a "suboptimal environment" with existing tax distortions. We then use the macroeconomic data from the Chongqing Municipality in China to conduct simulations to empirically test our analytic results. Our main findings include the followings. First, an increase in environmental tax rate can effectively reduce the use of polluting consumer goods by households as well as investment in polluting factors by enterprises. Hence, an increase in environmental tax rate can improve environmental quality and obtain "environmental dividend". Second, an increase in environmental tax rate can negatively impact employment, family income and economic growth. Hence, there is no "non-environmental dividend" effect. Third, an increased environmental tax rate has both substitution effect and income effect on household consumption. On the one hand, it motivates households to substitute polluting consumer goods with clean consumer goods. On the other hand, it lowers the total consumption level of households. Fourth, we show that the "double dividend" hypothesis on environmental tax is invalid. And the optimal environmental tax under the suboptimal environment is lower than the Pigouvian tax rate. Finally, we discuss the policy implications of our results.

Characterization and immunomodulatory activity of polysaccharides from the stems and leaves of Abelmoschus manihot and a sulfated derivative.

BACKGROUND: Abelmoschus manihot (Linn.) Medicus is a traditional herbal medicine whose flowers, stems and leaves exhibit widely pharmacological activities. However, only the flowers have long been used as medicine while the stems and leaves were mainly discarded and burned, which undoubtedly caused enormous waste of these resources and serious environment pollution. Many researches have indicated that bioactivities of polysaccharides were significantly improved after sulfation. The aim of this study was to investigate the characterization and immunomodulatory activity of polysaccharides from stems and leaves of A. manihot and a sulfated derivative. RESULTS: A mixed neutral polysaccharide (SLAMP-a) and two acidic polysaccharides (SLAMP-c and SLAMP-d) were obtained from stems and leaves of A. manihot by DEAE-cellulose chromatography. SLAMP-a was a water-insoluble mixture while its sulfated derivative (S-SLAMP-a3), prepared with aminosulfonic acid, was a homogeneous polysaccharide with excellent solubility. The average molecular weights of S-SLAMP-a3, SLAMP-c and SLAMP-d were 1044.2kDa, 477.8kDa and 264.2kDa respectively. SLAMP-a and its sulfate mainly contained glucose, and SLAMP-c and SLAMP-d were both composed of mannose, rhamnose, glucuronic acid, glucose, galactose, and arabinose. In vitro study indicated that S-SLAMP-a3, SLAMP-c and SLAMP-d exhibited significant immunomodulatory activity, while SLAMP-a showed little effects. CONCLUSION: SLAMP-c and SLAMP-d from A. manihot stems and leaves could be explored as immunomodulatory agents, which would provide a way to utilize these enormously discarded resources and avoid massive waste. Additionally, the neutral polysaccharide, SLAMP-a, could also be developed after sulfation, suggesting that these disused resources would be further used effectively.

Inhibitive effect of loureirin B plus capsaicin on tetrodotoxin-resistant sodium channel.

OBJECTIVE: To investigate whether the effect of loureirin B plus capsaicin on tetrodotoxin-resistant (TTX-R) sodium channel. METHODS: By using whole-cell patch-clamp recordings, in acutely isolated dorsal root ganglion (DRG) neurons, the combined effects of loureirin B and capsaicin on TTX-R sodium channel were observed. Based on the data, the interaction between loureirin B and capsaicin in their modulation on TTX-R sodium channel was assessed. RESULTS: Loureirin B could not induce transient inward TRPV1 current. Capsazepine, a transient receptor potential vanilloid l (TRPV1) antagonist, could not attenuate the block of 0.64 mmol/L loureirin B on TTX-R sodium channel. There was no significant difference (P > 0.05) between IC50 of loureirin B (0.37 mmol/L) on TTX-R sodium channel in capsaicin-sensitive DRG neurons and that (0.38 mmol/L) in capsaicin-insensitive DRG neurons. However, there was a significant difference (P < 0.05) between the IC50 of capsaicin (0.28 ¦Ìmol/L) on TTX-R sodium channel in capsaicin-sensitive DRG neurons and that (52.24 ¦Ìmol/L) in capsaicin-insensitive DRG neurons. Four combinations composed of various concentrations of loureirin B and capsaicin could all inhibit TTX-R sodium currents but have different interactions between loureirin B and capsaicin. CONCLUSION: Loureirin B plus capsaicin could produce double blockage on TRPV1 and modulation on TTX-R sodium channel. The action of loureirin B on TTX-R sodium channel was independent of TRPV1 but similar with that of capsaicin on TTX-R sodium channel in capsaicin-insensitive DRG neurons.

Dynamic changes of flavonoids in Abelmoschus manihot different organs at different growth periods by UPLC-MS/MS.

Abelmoschus manihot (Linn.) Medicus has been clinically used to treat chronic kidney disease, oral ulcers, burns, and dysmenorrhea in China for many centuries. The major pharmacologically-active components of A. manihot are flavonoids. In this study, a rapid and highly sensitive UPLC-MS/MS analysis method was established and successfully applied to the simultaneous determination of five major flavonoids (rutin, hyperoside, isoquercitrin, quercetin, and myricetin) in different parts of A. manihot harvested at ten growth periods. Under the optimized chromatographic conditions, good separation for five target components was obtained on an Acquity UPLC BEH C18 column within 18min. The total contents of the five investigated flavonoids in A. manihot roots, stems, leaves and flowers ranged from 2.86 to 123.7µg/g, 46.39 to 141.0µg/g, 929.4 to 3096µg/g, and 10,150 to 19,390µg/g, respectively, indicating that the total flavonoids in the four parts could be mainly arranged in a decreasing order as flower>leaf>stem>root. The peak of total flavonoids in flowers and leaves appeared at G8 and G9, respectively. These results will be helpful for the determination of the suitable harvest time of A. manihot and the improvement of the utility value of the disused parts.

Effect of 5-aminolevulinic acid photodynamic therapy on keratinocyte proliferation and apoptosis in condyloma acuminatum.

BACKGROUND: The effect of 5-aminolevulinic acid photodynamic therapy on keratinocyte proliferation and apoptosis in condyloma acuminatum tissues was evaluated. METHODS: An immunohistochemical method and TdT-mediated dUTP nick end labeling were performed to detect the positive expression of the keratinocyte proliferation-related gene Ki-67 and apoptosis, respectively, in condyloma acuminatum tissues. RESULTS: Of 52 cases, 44 showed positive expression of Ki-67 in condyloma acuminatum keratinocytes before the treatment, with a positive expression rate of 84.62% (44/52), an expression strength of mostly ++ - +++, and a Ki-67 proliferation index of 80.26±5.07%. After treatment, 22 cases showed positive expression of Ki-67 in condyloma acuminatum keratinocytes, with a positive expression rate of 42.31% (22/52), an expression strength of mostly - - ++, and a proliferation index of 42.67±3.06%. The differences in the positive expression rate, expression strength, and proliferation index in the before- and after-treatment groups were statistically significant (χ2=20.070, P<0.001). For visible apoptotic cells in condyloma acuminatum keratinocytes before the 5-aminolevulinic acid photodynamic treatment, the expression strength was mostly + - ++, and the average apoptotic index was 13.94±2.35%; after treatment, the expression strength was mostly ++ - +++, and the average apoptotic index was 73.88±7.65%; the difference in the apoptotic index between the before and after treatment groups was statistically significant (P<0.001). CONCLUSION: 5-Aminolevulinic acid photodynamic therapy can inhibit the proliferation and promote the apoptosis of keratinocytes, and represents an effective mechanism for treating condyloma acuminatum.

Enzymatic synthesizing of phytosterol oleic esters.

A method of synthesizing the phytosterol esters from oleic acid and sterols was studied, using immobilized lipase Candida sp. 99-125 as catalyst. Molar ratio (oleic acid/phytosterols), temperature, reaction period, organic solvents, catalyst, and silica-gel drier were optimized, and the result showed that 93.4% of the sterols had been esterified under the optimal synthetic condition: the molar ratio of oleic acid/phytosterol is 1:1 in 10 mL iso-octane, immobilized lipase (w, 140% of the sterols), incubated in an orbital shaker (200 rpm) at a temperature of 45 °C for 24 h. The immobilized lipase could be reused for at least 13 times with limited loss of esterification activity. The conversion still maintained up to 86.6%. Hence, this developed process for synthesizing phytosterol esters could be considered as simple and low-energy consumption compared to existing chemical processes.