Baicalin, silver titanate, Bletilla striata polysaccharide and carboxymethyl chitosan in a porous sponge dressing for burn wound healing.

OBJECTIVE: This study tests the efficacy of Bletilla striata polysaccharide (BSP), carboxymethyl chitosan (CMC), baicalin (BA) and silver titanate (ST) in a wound dressings to fight infection, promote healing and provide superior biocompatibility. METHODS: The antibacterial activity of BA and ST was evaluated in vitro using the inhibition zone method. BA/ST/BSP/CMC porous sponge dressings were prepared and characterized. The biocompatibility of BA/ST/BSP/CMC was assessed using the cell counting kit-8 assay. The therapeutic effect of BA/ST/BSP/CMC was further investigated using the dorsal skin burn model in Sprague-Dawley rats. RESULTS: The wound dressing had good antibacterial activity against Escherichia coli and Staphylococcus aureus through BA and ST, while the combination of BSP and CMC played an important role in promoting wound healing. The BA/ST/BSP/CMC porous sponge dressings were prepared using a freeze-drying method with the concentrations of BA and ST at 20 and 0.83 mg/mL, respectively, and the optimal ratio of 5% BSP to 4% CMC was 1:3. The average porosity, water absorption and air permeability of BA/ST/BSP/CMC porous sponge dressings were measured to be 90.43%, 746.1% and 66.60%, respectively. After treatment for 3 and 7 days, the healing rates of the BA/ST/BSP/CMC group and BA/BSP/CMC group were significantly higher than those of the normal saline (NS) group and silver sulfadiazine (SSD) group (P < 0.05). Interleukin-1ß expression in the BA/ST/BSP/CMC group at 1 and 3 days was significantly lower than that in the other three groups (P < 0.05). After being treated for 3 days, vascular endothelial growth factor expression in the BA/BSP/CMC group and BA/ST/BSP/CMC group was significantly higher than that in the NS group and SSD group (P < 0.05). Inspection of histological sections showed that the BA/ST/BSP/CMC group and BA/BSP/CMC group began to develop scabbing and peeling of damaged skin after 3 days of treatment, indicating accelerated healing relative to the NS group and SSD group. CONCLUSION: The optimized concentration of BA/ST/BSP/CMC dressing was as follows: 6 mg BSP, 14.4 mg CMC, 0.5 mg ST and 12 mg BA. The BA/ST/BSP/CMC dressing, containing antibacterial constituents, was non-cytotoxic and effective in accelerating the healing of burn wounds, making it a promising candidate for wound healing. Please cite this article as: Gong YR, Zhang C, Xiang X, Wang ZB, Wang YQ, Su YH, Zhang HQ. Baicalin, silver titanate, Bletilla striata polysaccharide and carboxymethyl chitosan in a porous sponge dressing for burn wound healing. J Integr Med. 2023; 21(5): 487-495.

Ensemble Multi-Quantiles: Adaptively Flexible Distribution Prediction for Uncertainty Quantification.

We propose a novel, succinct, and effective approach for distribution prediction to quantify uncertainty in machine learning. It incorporates adaptively flexible distribution prediction of [Formula: see text] in regression tasks. This conditional distribution's quantiles of probability levels spreading the interval (0,1) are boosted by additive models which are designed by us with intuitions and interpretability. We seek an adaptive balance between the structural integrity and the flexibility for [Formula: see text], while Gaussian assumption results in a lack of flexibility for real data and highly flexible approaches (e.g., estimating the quantiles separately without a distribution structure) inevitably have drawbacks and may not lead to good generalization. This ensemble multi-quantiles approach called EMQ proposed by us is totally data-driven, and can gradually depart from Gaussian and discover the optimal conditional distribution in the boosting. On extensive regression tasks from UCI datasets, we show that EMQ achieves state-of-the-art performance comparing to many recent uncertainty quantification methods. Visualization results further illustrate the necessity and the merits of such an ensemble model.

Cu(I) Metal-Organic Framework Composites with AgCl/Ag Nanoparticles for Irradiation-Enhanced Antibacterial Activity against E. coli.

Metal-organic frameworks (MOFs) have emerged as prospective antibacterial agents or synergistic agents for their versatile chemical building components and structures. In this work, copper(I) halide MOFs of Cu(I)bpyCl (bpy = 4,4'-bipyridine) composited with AgCl/Ag nanoparticles were synthesized, and their antibacterial activities were measured against Escherichia coli and Staphylococcus aureus. The attached chlorine in Cu(I)2Cl2 nodes of the MOFs served as loading sites for silver ions, in which AgCl and concomitant metallic Ag nanoparticles were in situ generated. Exceptional antibacterial activity against E. coli was realized with a minimum inhibitory concentration (MIC) of ∼7.8 µg mL-1, while the MIC value was ∼16 µg mL-1 against S. aureus. Enhanced antibacterial activity against E. coli with light irradiation was measured by the disk diffusion method compared with that under dark conditions.

Effect of Different Types of Hypoglycemic Medications on Psoriasis: An Analysis of Current Evidence.

BACKGROUND: Psoriasis is a chronic recurrent inflammatory skin disease with a high risk of diabetes based on disease severity. OBJECTIVES: The aim of the study was to evaluate the efficacy of different hypoglycemic medications in patients with psoriasis. METHODS: A systematic review and meta-analysis of studies were conducted to evaluate the efficacy of hypoglycemic medications in patients with psoriasis. The primary outcome was of changes in the psoriasis area and severity index (PASI) score, and a 75% improvement in PASI from baseline (PASI75). Subgroup analysis was used to investigate associations among the types of hypoglycemic medicines, combination therapy, patient characteristics, course of treatment, and curative effect. RESULTS: We included 3,286 patients from 19 studies to explore the effects of hypoglycemic medications. Patients randomized to receive hypoglycemic medicines showed a more significant decrease in the PASI score (standard mean difference = -0.55, 95% confidence interval (CI): -0.87 to -0.23, p = 0.0007) and a higher PASI75 ratio (RR: 1.80, 95% CI: 1.20-2.71, p = 0.0046). Patients consuming thiazolidinediones (TZDs) were more likely to reach PASI75 than those consuming glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase 4 inhibitors. The combined use of hypoglycemic medicines had an add-on effect on the standard psoriasis treatment, and the proportion of PASI75 in the combination group was nearly four times that in the noncombination group (p = 0.0216). In addition, hypoglycemic medications can reduce body weight, waist circumference, triglyceride, total cholesterol, low-density lipoprotein, and systolic blood pressure. CONCLUSIONS: Certain hypoglycemic drugs, such as GLP-1 RAs and TZDs, are beneficial for treating psoriasis. Multidisciplinary collaboration is recommended for the management of systemic inflammation in patients with psoriasis and diabetes.

Psoriasis complicated with metabolic disorder is associated with traditional Chinese medicine syndrome types: a hospital-based retrospective case-control study.

OBJECTIVE: To explore the distribution law of traditional Chinese medicine (TCM) syndrome types in patients with psoriasis vulgaris complicated by metabolic disorders based on the same pathogenic factors as blood-heat and blood-stasis in the pathogenesis of psoriasis and metabolic disorders and to further analyze the correlation between adiponectin and the distribution law. METHODS: From 1 January 2018 to 31 December 2019, patients diagnosed with psoriasis in the inpatient or outpatient department of Dermatology Ward of Shanghai Yueyang Hospital and normal participants who underwent physical examination in the physical examination center over the same period were retrospectively reviewed. Demographic data, medical history, metabolic disorder indices, and TCM syndrome indices of psoriasis patients and healthy volunteers were evaluated. RESULTS: We included 307 patients with psoriasis and 613 healthy controls. On analyzing past medical history, the proportion of overweight and obesity and the comorbidity of diabetes in the psoriasis group (53.42 and 14.66%) were significantly higher than in the control group (43.88 and 7.67%, respectively; p < .05). The abnormal rates of triglyceride (34.20%), high-density lipoprotein cholesterol (50.49%), and HbA1c (18.57%) levels in the psoriasis group were higher than those in the normal control group (26.75, 17.13, and 12.56%, respectively). Overall, the incidence of metabolic disorders in psoriasis patients (267/307, 86.97%) was higher than that in the normal controls (484/613, 78.96%). Among the different syndrome types, the blood-stasis group had significantly higher rates of hypertension, diabetes, and abnormal glycosylated hemoglobin (46.07, 19.10, and 24.72%, respectively) than those of the control group (27.57, 7.67, and 12.56%; p < .05). Patients with blood stasis syndrome had the highest metabolic disorder comorbidity rate (93.26%) and lowest adiponectin level (p < .05). CONCLUSIONS: TCM syndrome differentiation of psoriasis, especially the diagnosis of blood-stasis syndrome, prompts the early screening of patients with metabolic comorbidities. For patients with psoriasis with metabolic disorder, TCM for promoting blood circulation and removing blood stasis can be compatibly applied without contraindications. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov (Trial ID: NCT03942185).

TM4SF19-AS1 facilitates the proliferation of lung squamous cell carcinoma by recruiting WDR5 to mediate TM4SF19.

BACKGROUND: As reported, long non-coding RNAs are a pivotal player in lung squamous cell carcinoma (LSCC) progression. We noticed the remarkably upregulated transmembrane-4-l-six-family-19 antisense RNA 1 (TM4SF19-AS1) in LSCC and further demonstrated the function it played in LSCC and the possible molecular mechanism. METHODS: Via bioinformatics approach, we evaluated TM4SF19-AS1 and TM4SF19 levels in LSCC tissue, and real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot revealed their mRNA and protein levels in LSCC cells. Cell Counting Kit-8 and colony formation assays analyzed the proliferation ability of LSCC cells, and cell adhesion ability was detected via cell adhesion assay. RNA immunoprecipitation and chromatin immunoprecipitation analyzed the underlying mechanism of TM4SF19-AS1 regulating its target, while methylation-specific PCR indicated the methylation level of TM4SF19-AS1. RESULTS: TM4SF19-AS1 was markedly upregulated in LSCC. Functional assays revealed that TM4SF19-AS1 could facilitate the proliferation and adhesion of LSCC. Besides, we revealed the mechanism of TM4SF19-AS1 regulation that it directly bound to WD repeat-containing protein 5 (WDR5), and was then recruited to TM4SF19 promoter region, which activated DNA demethylation, thereby suppressing malignant LSCC progression. CONCLUSION: Our research demonstrated that TM4SF19-AS1 affected LSCC cell proliferation by recruiting WDR5 to manipulate transmembrane-4-lsix-family-member-19 (TM4SF19), which offers a new observation on LSCC pathogenesis, indicating that TM4SF19-AS1 is able to be a promising target for LSCC treatment.

Experimental Investigation of Unconfined Compression Strength and Microstructure Characteristics of Slag and Fly Ash-Based Geopolymer Stabilized Riverside Soft Soil.

To solve the issues of insufficient early strength of cement stabilized soil and high resource cost, high reduction cost, and high environmental cost induced by the application of cement, the slag and fly ash-based geopolymer was adopted as the stabilizer to treat riverside soft soil. This study mainly investigated the effects of stabilizer content, slag-to-fly ash ratio, and alkaline activator content on the strength of geopolymer stabilized soils with different curing ages. Unconfined compressive strength (UCS), scanning electron microscope (SEM), and X-ray energy spectrum analysis (EDS) tests were carried out. The results show that the stabilizer content, slag-fly ash ratio, and alkaline activator content have a decisive influence on the UCS of geopolymer-stabilized soil. The mix-proportions scheme of geopolymer stabilized riverside soft soil, with a geopolymer content of 15%, a slag-fly ash ratio of 80:20, and an alkaline activator content of 30%, is considered optimum. It is proven by SEM that the uniformly distributed gelatinous products formed in the geopolymer-stabilized soil bind the soil particles tightly. Moreover, the EDS analysis confirms that the gelatinous products are mainly composed of C-S-H gel and sodium-based aluminosilicate (N-A-S-H).

Design of dual targeting immunomicelles loaded with bufalin and study of their anti-tumor effect on liver cancer.

OBJECTIVE: Bufalin is an effective drug for the treatment of liver cancer. But its high toxicity, poor water-solubility, fast metabolism and short elimination half-life limit its use in tumor treatment. How to make the drug accumulate in the tumor and reduce side effects while maintaining its efficacy are urgent problems to be solved. The goal of this study is to solve these problems. METHODS: A copolymer with tunable poly-N-isopropylacrylamide and polylactic acid was designed and synthesized. The corresponding dual targeting immunomicelles (DTIs) loaded with bufalin (DTIs-BF) were synthesized by copolymer self-assembly in an aqueous solution. The size and structure of DTIs-BF were determined by ZetaSizer Nano-ZS and transmission electron microscopy. Then, its temperature sensitivity, serum stability, critical micelle concentration (CMC), entrapment efficiency (EE), drug release and non-cytotoxicity of blank block copolymer micelles (BCMs) were evaluated. Next, the effects of DTIs-BF on cellular uptake, cytotoxicity, and tumor cell inhibition were evaluated. Finally, the accumulation of DTIs-fluorescein isothiocyanate (FITC) and the in vivo anti-tumor effect were observed using an interactive video information system. RESULTS: DTIs-BF had a small size, spherical shape, good temperature sensitivity, high serum stability, low CMC, high EE, and slow drug release. The blank BCMs had very low cytotoxicity. Compared with free bufalin, the in vitro cellular internalization and cytotoxicity of DTIs-BF against SMMC-7721 cells were significantly enhanced, and the effects were obviously better at 40 °C than 37 °C. In addition, the therapeutic effect on SMMC-7721 cells was further enhanced by the programmed cell death specifically caused by bufalin. When DTIs-FITC were injected intravenously in BALB/c nude mice bearing liver cancer, the accumulation of FITC was significantly increased in tumors. CONCLUSION: DTIs-BF is a potentially effective nano-formulation and has broad prospects in the clinical treatment of liver cancer.

Effect of Accelerators on the Workability, Strength, and Microstructure of Ultra-High-Performance Concrete.

The preparation of ultra-high-performance concrete (UHPC) with both high-early-strength and good workability contributes to further promotion of its development and application. This study investigated the effects of different accelerators (SM, alkaline powder accelerator; SF, alkaline powder accelerator containing fluorine; and AF, alkali-free liquid accelerator containing fluorine) on the workability and strength properties of UHPC. The microstructure of UHPC was also characterized by using XRD and SEM. Several dosage levels of accelerators (2%, 4%, 6%, and 8% by mass) were selected. The results indicate that the setting time and fluidity of UHPC are gradually decreased with an increase in accelerators dosage. Compared with fluorine-containing SF/AF, fluorine-free SM evidently facilitates UHPC early strength gain speed. However, the fluorine-containing accelerators have a higher 28 d strength ratio, especially AF. The maximum compressive and flexural strength ratios are obtained at a dosage of 6%, which are 95.5% and 98.3%, respectively. XRD and SEM tests further reveal the effect of different accelerators on the macroscopic properties of UHPC from the micro level.

Determination of Endogenous Bufalin in Serum of Patients With Hepatocellular Carcinoma Based on HPLC-MS/MS.

Bufalin is a cardiotonic steroid and a key active ingredient of the Chinese medicine ChanSu. It has significant anti-tumor activity against many malignancies, including hepatocellular carcinoma (HCC). Previous studies have shown that human bodies contain an endogenous bufalin-like substance. This study aimed to confirm whether the endogenous bufalin-like substances is bufalin and further detect the differences between HCC and control groups of endogenous bufalin concentration by the high-performance liquid chromatography coupled tandem mass spectrometry (HPLC-MS/MS). The results confirmed the endogenous bufalin-like substance is bufalin. Totally, 227 serum samples were collected: 54 from HCC patients and 173 from healthy volunteers constituting a control group. Both the test group and the control group contained bufalin in serum, revealing that bufalin is indeed an endogenous substance. The bufalin concentration was 1.3 nM in HCC patients and 5.7 nM in normal people (P < 0.0001). These results indicate that human bodies contain endogenous bufalin, and it may be negatively correlated with the incidence of HCC.

Regulatory effects of four ginsenoside monomers in humoral immunity of systemic lupus erythematosus.

Ginsenosides Rb1, Rh1, Rg1 and Rg3 are known as the main active components extracted from the roots of the Panax ginseng C.A. Meyer, and were reported to have immunoregulatory effects. Disruption of B-cell immune regulation during the pathogenesis of systemic lupus erythematosus (SLE) may lead to the production of large amounts of antibodies. The present study investigated the effects of the four ginsenoside monomers on B-cell immune regulation and observed that they inhibited the proliferation and secretion of B cells induced by LPS, caused an upregulation of the expression of apoptosis-associated proteins Fas/Fas ligand and caspase-3, the expression of FcγRIIB (CD32) as well as the proportion of inactive B cells (CD19+CD27-). These results indicate that Rb1, Rh1, Rg1 and Rg3 inhibit the humoral immunity of SLE, among which Rh1 exhibited the most obvious inhibitory effect.

Characteristic Analysis of Complementary and Alternative Medicine in Randomized Controlled Trials of Oncology: A Comparison of Published Studies.

BACKGROUND: Complementary and alternative medicine (CAM) has been widely used by cancer patients and oncologists in the past decades. The present study aimed to examine and compare the characteristics and registration status of published studies in a sample of recently published CAM randomized controlled trial (RCT) reports of oncology in leading journals of 3 categories: general and internal medicine (GIM), clinical oncology (CO), and CAM. METHODS: Articles published in the top 5 journals of the 3 categories from 2006 to 2015 were searched in PubMed. Basic characteristics, registration information, impact factor, and citations were identified and extracted from the included RCTs. Data were summarized by frequency, mean, and median and compared using χ2 test and Kruskal-Wallis H test. RESULTS: A total of 59 RCTs were included; among them, 34 (58%) could be identified with a registration number. GIM journals (15) enjoyed the highest average number of citations per article, followed by CO (12) and CAM (3) journals ( P < .0001). ClinicalTrials.gov was the most popular registry for these RCTs. Of the RCTs registered in ClinicalTrials.gov , 24% (4/17) of the published studies in CO journals put their results in the registry; however, no study in GIM and CAM journals put the result in the registry ( P = .372). CONCLUSION: The top GIM, CO, and CAM journals rarely published CAM RCTs of oncology from 2006 to 2015, and the CAM articles of oncology were less cited. However, there was a clear improvement in the trial registration rate over the past decades.

Bufalin-loaded bovine serum albumin nanoparticles demonstrated improved anti-tumor activity against hepatocellular carcinoma: preparation, characterization, pharmacokinetics and tissue distribution.

OBJECTIVE: To prepare and evaluate the liver-targeted drug delivery system of Bufalin with higher liver uptake and stronger antitumor activity against hepatocellular carcinoma. METHODS: Bufalin-loaded bovine serum albumin nanoparticle was prepared by desolvation method, to investigate the in vitro release performance and to evaluate the pharmacokinetic and tissue distribution. The antitumor activity against hepatocellular carcinoma was evaluated in vitro and in vivo, respectively. RESULTS: The Bufalin-loaded bovine serum albumin nanoparticle with an average particle size of 125.1 nm exhibited a sustained release behavior in vitro. The half-life, blood plasma area under the curve and apparent volume of distribution of Bufalin-loaded bovine serum albumin nanoparticle were significantly higher than that of Bufalin, whereas the clearance rate was lower than Bufalin group. The uptake of liver for Bufalin-loaded bovine serum albumin nanoparticle was 352.045 ± 35.665 ng/g while for Bufalin was 164.465 ± 48.080 ng/g (P < 0.01) at 5 min. The uptake of tumor for Bufalin-loaded bovine serum albumin nanoparticle was significantly higher than that of Bufalin both at 5 min (50.169 ± 11.708 ng/g, 93.415±13.828 ng/g, P < 0.01) and 15 min (43.683 ± 11.499 ng/g, 64.219 ± 17.684 ng/g, P > 0.05). Bufalin-loaded bovine serum albumin nanoparticle and Bufalin have similar antitumor activity in vitro. The tumor inhibition effect of Bufalin-loaded bovine serum albumin nanoparticle was stronger than that of Bufalin alone in vivo. CONCLUSION: Bufalin-loaded bovine serum albumin nanoparticle is a promising liver-targeted drug delivery system with higher liver uptake and stronger antitumor activity against hepatocellular carcinoma.

Successful in vivo hyperthermal therapy toward breast cancer by Chinese medicine shikonin-loaded thermosensitive micelle.

The Chinese traditional medicine Shikonin is an ideal drug due to its multiple targets to tumor cells. But in clinics, improving its aqueous solubility and tumor accumulation is still a challenge. Herein, a copolymer with tunable poly(N-isopropylacrymaide) and polylactic acid block lengths is designed, synthesized, and characterized in nuclear magnetic resonance. The corresponding thermosensitive nanomicelle (TN) with well-defined core-shell structure is then assembled in an aqueous solution. For promoting the therapeutic index, the physical-chemistry properties of TNs including narrow size, low critical micellar concentration, high serum stability, tunable volume phase transition temperature (VPTT), high drug-loading capacity, and temperature-controlled drug release are systematically investigated and regulated through the fine self-assembly. The shikonin is then entrapped in a degradable inner core resulting in a shikonin-loaded thermosensitive nanomicelle (STN) with a VPTT of ~40°C. Compared with small-molecular shikonin, the in vitro cellular internalization and cytotoxicity of STN against breast cancer cells (Michigan Cancer Foundation-7) are obviously enhanced. In addition, the therapeutic effect is further enhanced by the programmed cell death (PCD) specifically evoked by shikonin. Interestingly, both the proliferation inhibition and PCD are synergistically promoted as T > VPTT, namely the temperature-regulated passive targeting. Consequently, as intravenous injection is administered to the BALB/c nude mice bearing breast cancer, the intratumor accumulation of STNs is significantly increased as T > VPTT, which is regulated by the in-house developed heating device. The in vivo antitumor assays against breast cancer further confirm the synergistically enhanced therapeutic efficiency. The findings of this study indicate that STN is a potential effective nanoformulation in clinical cancer therapy.

Investigating the potential of Shikonin as a novel hypertrophic scar treatment.

BACKGROUND: Hypertrophic scarring is a highly prevalent condition clinically and results from a decreased number of apoptotic fibroblasts and over-abundant production of collagen during scar formation following wound healing. Our previous studies indicated that Shikonin, an active component extracted from Radix Arnebiae, induces apoptosis and reduces collagen production in hypertrophic scar-derived fibroblasts. In the study reported here, we further evaluate the potential use of Shikonin as a novel scar remediation therapy by examining the effects of Shikonin on both keratinocytes and fibroblasts using Transwell® co-culture techniques. The underlying mechanisms were also revealed. In addition, effects of Shikonin on the expression of cytokines in Transwell co-culture "conditioned" medium were investigated. RESULTS: Our results indicate that Shikonin preferentially inhibits cell proliferation and induces apoptosis in fibroblasts without affecting keratinocyte function. In addition, we found that the proliferation-inhibiting and apoptosis-inducing abilities of SHI might be triggered via MAPK and Bcl-2/Caspase 3 signalling pathways. Furthermore, SHI has been found to attenuate the expression of TGF-ß1 in Transwell co-cultured "conditioned" medium. CONCLUSIONS: The data generated from this study provides further evidence that supports the potential use of Shikonin as a novel scar remediation therapy.

Shikonin reduces TGF-ß1-induced collagen production and contraction in hypertrophic scar-derived human skin fibroblasts.

Hypertrophic scarring/hypertrophic scars (HS) is a highly prevalent condition following burns and trauma wounds. Numerous studies have demonstrated that transforming growth factor-ß1 (TGF­ß1) plays an essential role in the wound healing process by regulating cell differentiation, collagen production and extracellular matrix degradation. The increased expression of TGF-ß1 is believed to result in the formation of HS. Shikonin (SHI), an active component extracted from the Chinese herb, Radix Arnebiae, has previously been found to downregulate the expression of TGF-ß1 in keratinocyte/fibroblast co-culture conditioned medium. In view of this, in this study, we aimed to further investigate the effects of SHI on TGF-ß1-stimulated hypertrophic scar-derived human skin fibroblasts (HSFs) and examined the underlying mechanisms. Cell viability and proliferation were measured using alamarBlue and CyQUANT assays. The total amount of collagen and cell contraction were examined using Sirius red staining and the cell contraction assay kit. Gene expression and signalling pathway activation were detected using reverse transcription-quantitative polymerase chain reaction and western blot analysis. Our results revealed that SHI reduced TGF-ß1­induced collagen production through the ERK/Smad signalling pathway and attenuated TGF-ß1­induced cell contraction by downregulating α-smooth muscle actin (αSMA) expression in the HSFs. The data from this study provide evidence supporting the potential use of SHI as a novel treatment for HS.

Functional and mechanistic investigation of Shikonin in scarring.

Scarring is a significant medical burden; financially to the health care system and physically and psychologically for patients. Importantly, there have been numerous case reports describing the occurrence of cancer in burn scars. Currently available therapies are not satisfactory due to their undesirable side-effects, complex delivery routes, requirements for long-term use and/or expense. Radix Arnebiae (Zi Cao), a perennial herb, has been clinically applied to treat burns and manage scars for thousands of years in Asia. Shikonin, an active component extracted from Radix Arnebiae, has been demonstrated to induce apoptosis in cancer cells. Apoptosis is an essential process during scar tissue remodelling. It was therefore hypothesized that Shikonin may induce apoptosis in scar-associated cells. This investigation presents the first detailed in vitro study examining the functional responses of scar-associated cells to Shikonin, and investigates the mechanisms underlying these responses. The data obtained suggests that Shikonin inhibits cell viability and proliferation and reduces detectable collagen in scar-derived fibroblasts. Further investigation revealed that Shikonin induces apoptosis in scar fibroblasts by differentially regulating the expression of caspase 3, Bcl-2, phospho-Erk1/2 and phospho-p38. In addition, Shikonin down-regulates the expression of collagen I, collagen III and alpha-smooth muscle actin genes hence attenuating collagen synthesis in scar-derived fibroblasts. In summary, it is demonstrated that Shikonin induces apoptosis and decreases collagen production in scar-associated fibroblasts and may therefore hold potential as a novel scar remediation therapy.

A rapid and sensitive liquid chromatography-tandem mass spectrometric method for determination of actinoside E in rat plasma and application to a pharmacokinetic study.

A highly sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the determination of actinoside E in rat plasma. The analytes were extracted by ethyl acetate and an analogue of actinoside F was used as the internal standard. The mobile phase consisted of methanol-water (50: 50, V/V) containing 0.1% formic acid was delivered at a flow rate of 0.3 mL·min(-1) to a Zorbax SB-C18 column (100 mm × 2.1 mm, 3.5 µm). The detection was performed by electrospray ionization mass spectrometry in the negative multiple reaction monitoring mode with a chromatograph run time of 3.0 min. Calibration curves of actinoside E were linear in the range of 0.5-2 500 ng·mL(-1). In this range, intra- and inter-day precision ranged from 1.7% to 7.5% and 2.0% to 8.9%, respectively. The accuracy ranged from 95.7% to 108.6%, and extraction recovery from 83.2% to 85.5%. This method was successfully applied to a pharmacokinetic study of actinoside E in rats after intravenous (5 mg·kg(-1)) and oral (100 mg·kg(-1)) administration, and the results showed that actinoside E was poorly absorbed with an absolute bioavailability being approximately 0.27%.

Hepatoprotective Activity of the Total Saponins from Actinidia valvata Dunn Root against Carbon Tetrachloride-Induced Liver Damage in Mice.

The protective activity of the total saponins from Actinidia valvata Dunn root (TSAV) was studied against carbon-tetrachloride- (CCl(4)-) induced acute liver injury in mice. Mice were orally administered TSAV (50, 100, and 200 mg/kg) for five days and then given CCl(4). TSAV pretreatment significantly prevented the CCl(4)-induced hepatic damage as indicated by the serum marker enzymes (AST, ALT, and ALP). Parallel to these changes, TSAV also prevented CCl(4)-induced oxidative stress by inhibiting lipid peroxidation (MDA) and restoring the levels of antioxidant enzymes (SOD, CAT, GR, and GPX), GSH and GSSG. In addition, TSAV attenuated the serum TNF-α and IL-6 levels and inhibited the serum iNOS and NO levels. Liver histopathology indicated that TSAV alleviated CCl(4)-induced inflammatory infiltration and focal necrosis. TSAV (200 mg/kg) also significantly decreased Bak, Bax mRNA and Fas, FasL, p53, and NF-κB p65 protein expressions and increased Bcl-2 mRNA and protein expressions. Meanwhile, TSAV significantly downregulated caspase-3 and caspase-8 activities and prevented CCl(4)-induced hepatic cell apoptosis. In addition, TSAV exhibited antioxidant activity through scavenging hydroxyl and DPPH free radicals in vitro. These results indicated that TSAV could protect mice against CCl(4)-induced acute liver damage possibly through antioxidant, anti-inflammatory activities and regulating apoptotic-related genes.

New triterpenoids with cytotoxic activity from actinidia valvata.

Two new triterpenoids, 30-O-beta-D-glucopyranosyloxy-2alpha,3alpha,24-trihydroxyurs-12,18-diene-28-oic acid O-beta-D-glucopyranosyl ester (1) and 2alpha,3beta,3,30-tetrahydroxyurs-12,18-diene-28-oic acid O-beta-D-glucopyranosyl ester (2) were isolated from roots of Actinidia valvata Dunn. Their structures were elucidated by means of extensive spectroscopic studies. Both these two new compounds showed moderate cytotoxic activity in vitro against BEL-7402 and SMMC-7721 tumor cell line.