Antimicrobial efficacy of aloe-emodin mediated photodynamic therapy against antibiotic-resistant Pseudomonas aeruginosa in vitro.

Multidrug-resistant Pseudomonas aeruginosa is a common pathogen that causes topical infections following burn injuries. Antimicrobial photodynamic therapy (aPDT) has emerged as a promising approach for treating antibiotic-resistant bacterial infections. The objective of this study was to evaluate the aPDT efficacy of aloe-emodin (AE), which is a photosensitizer extracted from traditional Chinese herbs, on antibiotic-sensitive and antibiotic-resistant P. aeruginosa in vitro. In this study, we confirmed the effectiveness of AE-mediated aPDT against both standard and MDR P. aeruginosa, explored the effects of irradiation time and AE concentration on bacterial survival in AE-mediated aPDT, and observed the structural damage of P. aeruginosa by using transmission electron microscope. Our results showed that neither AE nor light irradiation alone caused cytotoxic effects on P. aeruginosa. However, AE-mediated aPDT effectively inactivated both antibiotic-sensitive and antibiotic-resistant P. aeruginosa. The transmission electron microscope investigation showed that aPDT mediated by AE primarily caused damage to the cytoplasm and cell membrane. Our findings suggest that AE is a photosensitizer in the aPDT of MDR P. aeruginosa-caused topical infections following burn injuries. Future investigations will concentrate on the safety and efficacy of AE-mediated aPDT in animal models and clinical trials.

[Cardiovascular complications in malaria: a review].

Malaria, one of the major global public health events, is a leading cause of mortality and morbidity among children and adults in tropical and subtropical regions(mainly in sub-Saharan Africa), threatening human health. It is well known that malaria can cause various complications including anemia, blackwater fever, cerebral malaria, and kidney damage. Conventionally, cardiac involvement has not been listed as a common reason affecting morbidity and mortality of malaria, which may be related to ignored cases or insufficient diagnosis. However, the serious clinical consequences such as acute coronary syndrome, heart failure, and malignant arrhythmia caused by malaria have aroused great concern. At present, antimalarials are commonly used for treating malaria in clinical practice. However, inappropriate medication can increase the risk of cardiovascular diseases and cause severe consequences. This review summarized the research advances in the cardiovascular complications including acute myocardial infarction, arrhythmia, hypertension, heart failure, and myocarditis in malaria. The possible mechanisms of cardiovascular diseases caused by malaria were systematically expounded from the hypotheses of cell adhesion, inflammation and cytokines, myocardial apoptosis induced by plasmodium toxin, cardiac injury secondary to acute renal failure, and thrombosis. Furthermore, the effects of quinolines, nucleoprotein synthesis inhibitors, and artemisinin and its derivatives on cardiac structure and function were summarized. Compared with the cardiac toxicity of quinolines in antimalarial therapy, the adverse effects of artemisinin-derived drugs on heart have not been reported in clinical studies. More importantly, the artemisinin-derived drugs demonstrate favorable application prospects in the prevention and treatment of cardiovascular diseases, and are expected to play a role in the treatment of malaria patients with cardiovascular diseases. This review provides reference for the prevention and treatment of malaria-related cardiovascular complications as well as the safe application of antimalarials.

Proximal tubular Bmal1 protects against chronic kidney injury and renal fibrosis by maintaining of cellular metabolic homeostasis.

Recent studies suggest that deletion of the core clock gene Bmal1 in the kidney has a significant influence on renal physiological functions. However, the role of renal Bmal1 in chronic kidney disease (CKD) remains poorly understood. Here by generating mice lacking Bmal1 in proximal tubule (Bmal1flox/flox-KAP-Cre+, ptKO) and inducing CKD with the adenine diet model, we found that lack of Bmal1 in proximal tubule did not alter renal water and electrolyte homeostasis. However, adenine-induced renal injury indexes, including blood urea nitrogen, serum creatinine, and proteinuria, were markedly augmented in the ptKO mice. The ptKO kidneys also developed aggravated tubulointerstitial fibrosis and epithelial-mesenchymal transformation. Mechanistically, RNAseq analysis revealed significant downregulation of the expression of genes related to energy and substance metabolism, in particular fatty acid oxidation and glutathione/homocysteine metabolism, in the ptKO kidneys. Consistently, the renal contents of ATP and glutathione were markedly reduced in the ptKO mice, suggesting the disruption of cellular metabolic homeostasis. Moreover, we demonstrated that Bmal1 can activate the transcription of cystathionine ß-synthase (CBS), a key enzyme for homocysteine metabolism and glutathione biosynthesis, through direct recruitment to the E-box motifs of its promoter. Supporting the in vivo findings, knockdown of Bmal1 in cultured proximal tubular cells inhibited CBS expression and amplified albumin-induced cell injury and fibrogenesis, while glutathione supplementation remarkably reversed these changes. Taken together, we concluded that deletion of Bmal1 in proximal tubule may aggravate chronic kidney injury and exacerbate renal fibrosis, the mechanism is related to suppressing CBS transcription and disturbing glutathione related metabolic homeostasis. These findings suggest a protective role of Bmal1 in chronic tubular injury and offer a novel target for treating CKD.

Comparative Study of Biochar Modified with Different Functional Groups for Efficient Removal of Pb(II) and Ni(II).

The potential application of biochar in water treatment is attracting interest due to its sustainability and low production cost. In the present study, H3PO4-modified porous biochar (H-PBC), ethylenediaminetetraacetic acid-modified porous biochar (E-PBC), and NaOH-modified porous biochar (O-PBC) were prepared for Ni(II) and Pb(II) adsorption in an aqueous solution. Scanning electron microscopy (SEM), X-ray diffraction analysis (XRD), Brunauer-Emmett-Teller analysis (BET), and Fourier-transform infrared (FT-IR) spectroscopy were employed to characterize the as-obtained samples, and their capacities for Ni(II) and Pb(II) adsorption were determined. SEM showed that H-PBC retained the hierarchical porous structure of pristine biochar. FT-IR showed that H-PBC possessed abundant oxygen-containing and phosphorus-containing functional groups on the surface. BET analysis demonstrated that the surface areas of H-PBC (344.17 m2/g) was higher than O-PBC (3.66 m2/g), and E-PBC (1.64 m2/g), respectively. H-PBC, E-PBC, and O-PBC all exhibited excellent performance at Ni(II) and Pb(II) adsorption with maximum adsorption capacity of 64.94 mg/g, 47.17 mg/g, and 60.24 mg/g, and 243.90 mg/g, 156.25 mg/g, and 192.31 mg/g, respectively, which were significantly higher than the adsorption capacity (19.80 mg/g and 38.31 mg/g) of porous biochar (PBC). Pseudo-second order models suggested that the adsorption process was controlled by chemical adsorption. After three regeneration cycles, the Ni(II) and Pb(II) removal efficiency with H-PBC were still 49.8% and 56.3%. The results obtained in this study suggest that H-PBC is a promising adsorbent for the removal of heavy metals from aqueous solutions.

Shikonin Attenuates Cochlear Spiral Ganglion Neuron Degeneration by Activating Nrf2-ARE Signaling Pathway.

The molecular mechanisms that regulate the proliferation and differentiation of inner ear spiral ganglion cells (SGCs) remain largely unknown. Shikonin (a naphthoquinone pigment isolated from the traditional Chinese herbal medicine comfrey root) has anti-oxidation, anti-apoptosis and promoting proliferation and differentiation effects on neural progenitor cells. To study the protective effect of shikonin on auditory nerve damage, we isolated spiral ganglion neuron cells (SGNs) and spiral ganglion Schwann cells (SGSs) that provide nutrients in vitro and pretreated them with shikonin. We found that shikonin can reduce ouabain, a drug that can selectively destroy SGNs and induce auditory nerve damage, caused SGNs proliferation decreased, neurite outgrowth inhibition, cells apoptosis and mitochondrial depolarization. In addition, we found that shikonin can increase the expression of Nrf2 and its downstream molecules HO-1 and NQO1, thereby enhancing the antioxidant capacity of SGNs and SGSs, promoting cells proliferation, and inhibiting cells apoptosis by activating the Nrf2/antioxidant response elements (ARE) signal pathway. However, knockdown of Nrf2 rescued the protective effect of shikonin on SGNs and SGSs damage. In addition, we injected shikonin pretreatment into mouse that ouabain-induced hearing loss and found that shikonin pretreatment has a defensive effect on auditory nerve damage. In summary, the results of this study indicate that shikonin could attenuate the level of oxidative stress in SGNs and SGSs through the Nrf2-ARE signaling pathway activated, induce the proliferation and differentiation of SGNs, and thereby improve the neurological hearing damage in mice. Therefore, shikonin may be a candidate therapeutic drug for endogenous antioxidants that can be used to treat neurological deafness.

Aloe-emodin-mediated antimicrobial photodynamic therapy against dermatophytosis caused by Trichophyton rubrum.

Trichophyton rubrum is responsible for the majority of dermatophytosis. Current systemic and topical antifungals against dermatophytosis are often tedious and sometimes unsatisfactory. Antimicrobial photodynamic therapy (aPDT) is a non-invasive alternative suitable for the treatment of superficial fungal infections. This work investigated the photodynamic inactivation efficacy and effects of aloe-emodin (AE), a natural photosensitizer (PS) against T. rubrum microconidia in vitro, and evaluated the treatment effects of AE-mediated aPDT for T. rubrum-caused tinea corporis in vivo and tinea unguium ex vivo. The photodynamic antimicrobial efficacy of AE on T. rubrum microconidia was evaluated by MTT assay. The inhibition effect of AE-mediated aPDT on growth of T. rubrum was studied. Intracellular location of AE, damage induced by AE-mediated aPDT on cellular structure and surface of microconidia and generation of intracellular ROS were investigated by microscopy and flow cytometry. The therapeutic effects of AE-mediated aPDT against dermatophytosis were assessed in T. rubrum-caused tinea corporis guinea pig model and tinea unguium ex vivo model. AE-mediated aPDT effectively inactivated T. rubrum microconidia in a light energy dose-dependent manner and exhibited strong inhibitory effect on growth of T. rubrum. Microscope images indicated that AE is mainly targeted to the organelles and caused damage to the cytoplasm of microconidia after irradiation through generation of abundant intracellular ROS. AE-mediated aPDT demonstrated effective therapeutic effects for T. rubrum-caused tinea corporis on guinea pig model and tinea unguium in ex vivo model. The results obtained suggest that AE is a potential PS for the photodynamic treatment of dermatophytosis caused by T. rubrum, but its permeability in skin and nails needs to be improved.

Front-Line Therapy in EGFR Exon 19 Deletion and 21 Leu858Arg Mutations in Advanced Non-Small Cell Lung Cancer: A Network Meta-Analysis.

OBJECTIVE: This study aimed to compare the efficacy of different first-line strategies based on different EGFR mutation types (19 deletion and 21 Leu858Arg mutations). METHODS: We conducted a systematic review and network meta-analysis (NMA) by searching and analyzing RCTs on PubMed, Embase, Cochrane Library, ASCO.org, and ESMO.org, from inception to September 30th, 2020. RESULTS: Nineteen RCTs involving 5450 patients were finally included in this study, covering 10 different treatment strategies. The Bayesian ranking results suggested that, in terms of PFS, in the overall population and in patients with 19del mutation, osimertinib was most likely to rank the first, with the cumulative probabilities of 41.89% and 45.73%, respectively, while for patients with 21 Leu858Arg mutation, standard of care (SoC, represents first-generation EGFR-TKIs in this NMA) + chemotherapy was most likely to rank the first, with the cumulative probabilities of 30.81% in PFS. Moreover, SoC + chemotherapy provided the best overall survival benefit for the overall population and patients with 19del, with the cumulative probabilities of 57.85% and 33.51%, respectively. In contrast, for patients with 21 Leu858Arg mutation, dacomitinib showed the most favorable overall survival, with the cumulative probabilities of 36.73%. CONCLUSIONS: In this NMA, osimertinib and SoC combined with chemotherapy would be the optimal first-line treatment options for advanced NSCLC patients harboring EGFR 19 deletion mutation and 21 Leu858Arg mutation, respectively. This finding is likely to be adopted in clinical practice and provide guidance for future clinical study design. Systematic review registration: INPLASY2020100059.

Aloe-emodin-mediated antimicrobial photodynamic therapy against multidrug-resistant Acinetobacter baumannii: An in vivo study.

BACKGROUND AND AIM: Antimicrobial photodynamic therapy (aPDT) has shown great potential for treatment of superficial or localized multidrug-resistant (MDR) Acinetobacter baumannii infections. The purpose of this study was to investigate the cytotoxicity and in vivo safety of aloe-emodin (AE), and its photodynamic treatment efficacy against MDR A. baumannii infections. METHODS: The cytotoxicity (dark toxicity) and phototoxicity of AE to human immortalized keratinocytes and mice fibroblasts were detected by CCK-8 kit. Low and high doses of AE were intravenously injected into mice to evaluate the safety of AE in vivo. Bioluminescent MDR A. baumannii strain was employed to establish the infection model on BALB/c mice after skin scald, and infection status and therapeutic effect of AE-mediated aPDT were assessed by animal imaging system. The peripheral blood of mice was analyzed by flow cytometer. RESULTS: AE had low cytotoxicity to human immortalized keratinocytes and mice fibroblasts, and had certain phototoxicity to these cells under light irradiation. The in vivo experiments demonstrated that AE caused no obvious effects on the weight and pathological changes of mice. AE-mediated aPDT was effective in the treatment of MDR A. baumannii caused infections in mice after skin scald. CONCLUSIONS: AE has potential to be used in the photodynamic treatment of MDR A. baumannii caused superficial infections after scald.

Sinomenine inhibits hypoxia induced breast cancer side population cells metastasis by PI3K/Akt/mTOR pathway.

Sinomenine is an alkaloid derived from Chinese medicinal plant Sinomenium acutum. Our previous studies suggested that sinomenine can inhibit the metastasis of breast cancer. However, whether sinomenine can inhibit the metastasis characteristics of breast cancer side population (SP) cells is still unknown. In present study, we isolated the side population (SP) cells from MDA-MB-231 cells by fluorescence-activated cell sorting (FACS). MDA-MB-231 SP cells were treated with different concentrations of sinomenine at the absence or presence of hypoxia, and cell viability were measured by CCK-8 assay. The transwell invasive assay were conducted to assess of the effect of sinomenine on the invasion of hypoxic MDA-MB-231 SP cells. The protein expression was detected by Western blot assay. Sinomenine inhibited the cell viability and invasion of hypoxic MDA-MB-231 SP cells. Western blot assay results showed that the upregulation of MMP-2 and MMP-9 by hypoxia was inversed by sinomenine. Additionally, it was found that sinomenine suppressed the activation of PI3K/Akt/mTOR pathway under hypoxia in MDA-MB-231 SP cells. Moreover, the inhibiton of sinomenine on metastasis of hypoxic MDA-MB-231SP cells and PI3K/Akt/mTOR pathway could be rescued by PI3K activator IGF-1. Our study suggested that sinomenine inhibits invasion of breast cancer SP cells under hypoxia through PI3K/Akt/mTOR pathway.

The effects of aloe emodin-mediated antimicrobial photodynamic therapy on drug-sensitive and resistant Candida albicans.

The extensive and repetitive use of antifungal drugs has led to the development of drug-resistant Candida albicans. Antimicrobial photodynamic therapy (aPDT) has received considerable attention as an emerging and promising approach to combat drug-resistant microbes. This study evaluated the photodynamic effects mediated by aloe emodin (AE), a natural compound isolated from Aloe vera and Rheum palmatum, on azole-sensitive and azole-resistant C. albicans in vitro. AE exhibited no significant dark toxicity, but in the presence of light, effectively inactivated C. albicans cells in a concentration-dependent manner. The uptake of AE by fungal cells was investigated by confocal laser scanning microscopy (CLSM), and the results showed that AE possessed stronger ability to enter into C. albicans cells following light irradiation. Transmission electron microscopy analysis suggested that AE-mediated aPDT could induce damage to the cell wall, cytoplasm, and nucleus. Damage to the surface of C. albicans was observed by scanning electron microscopy. These results suggest that AE is a potential PS for use in aPDT of drug-resistant C. albicans strains, and AE-mediated aPDT shows promise as an antifungal treatment.

CD13-specific ligand facilitates Xanthatin nanomedicine targeting dendritic cells for therapy of refractory allergic rhinitis.

Relapse in Allergic Rhinitis (AR) is triggered by various unclear mechanisms. Xanthium strumarium L. as a traditional folk medicine can inhibit inflammatory responses through multiple mechanisms. Xanthatin (XT) is a bioactive compound derived from Xanthium strumarium L, and we developed a polymeric micelle (PM) that is dendritic cells (DCs)-specific targeting delivery system loading XT (NGR-XT-PM) based on a cyclic peptide moiety (NGR) to render DCs maturation-resistant for therapy of refractory AR. A murine model of AR was employed to investigate the in vivo therapeutic efficiency and relapse rate compared with the commercial product Budesonide. The results showed intranasal administration of NGR-XT-PM presented significant anti-allergy effect with no recurrence, in contrast, all mice treatment with Budesonide relapsed. NGR-XT-PM could effectively reverse the Th1/Th2 imbalance by depleting the serum inflammatory levels (IgE, histamine and IL-4) and DCs surface costimulatory molecules (CD80, CD86 and I-A/I-E), and promote immune tolerance by upregulating the level of Treg cells and reducing the levels of Th2, Th9 and Th17 cells. Furthermore, we appealed to virtual screening of inflammatory targets and found XT blocking the COX-2/PGE2 signaling pathway, which is a key effector in immune responses. These indicated CD13-specific NGR could facilitate XT selectively targeting DCs for efficiently ameliorating refractory rhinitis, and NGR-XT-PM should be a potential anti-AR drug.

Antimicrobial photodynamic therapy against multidrug-resistant Acinetobacter baumannii clinical isolates mediated by aloe-emodin: An in vitro study.

BACKGROUND AND AIM: Antimicrobial photodynamic therapy (aPDT) has received considerable attention as an emerging and promising approach for treating superficial infections. The aim of this study was to investigate aPDT mediated by aloe emodin (AE), a natural compound isolated from Aloe vera and Rheum palmatum, against multidrug-resistant (MDR) Acinetobacter baumannii clinical isolates in vitro. METHODS: The photodynamic inactivation (PDI) efficacies of AE on three MDR A. baumannii isolates were assessed by colony forming units (CFU) assay. The aPDT effects mediated by AE on the genomic DNA, membrane integrity, and cellular structure of MDR A. baumannii were also investigated. RESULTS: AE showed no obvious dark toxicity, but inactivated the MDR A. baumannii isolates in an AE concentration and light energy dose-dependent manner. Agarose gel electrophoresis and LIVE/DEAD BacLight Bacterial Viability kit assay indicated that the genomic DNA and membrane integrity of MDR A. baumannii were damaged after AE-mediated aPDT treatment. Transmission electron microscopy (TEM) images demonstrated that AE-mediated aPDT could induce rupture of bacterial cell wall and membrane, and condensation of ribosomes in the cytoplasm. CONCLUSIONS: The results obtained in this study suggested that AE could serve as a potential antibacterial photosensitizer in the treatment of superficial infections caused by MDR A. baumannii.

[Effect of Influent C/N Ratio on the Nutrient Removal Characteristics of SNEDPR Systems].

To determine the performance of nitrogen and phosphorus removal within a simultaneous nitrification endogenous denitrification system (SNEDPR), an extended anaerobic/low aerobic (dissolved oxygen:0.5-2.0 mg·L-1)-operated sequencing batch reactor (SBR) was fed with simulation wastewater. The SBR was initiated under a constant influent C/N ratio of 10, with the simultaneous enrichment of polyphosphate-accumulating organisms (PAOs). It was then investigated at different influent C/N ratios of 10, 7.5, 5, and 2.5. The experimental results indicated that, when the influent C/N ratio was 10, SNEDPR could be successfully started up. The effluent PO43--P and total nitrogen (TN) concentrations were 0.1 mg·L-1 and 8.1 mg·L-1. PO43--P efficiency, TN efficiency, and SNED efficiency were 99.79%, 89.38%, and 58.0%, respectively. When the influent C/N ratio increased from 5 to 10, the nitrogen and phosphorus removal performance of the system improved with PRA, and SNED efficiency increased from 16.0 m·L-1 and 48.0% to 24.4 mg·L-1 and 69.2%, respectively. When the C/N ratio was 10, the TN and PO43--P removal efficiencies increased to 94.5% and 100%, respectfully. When the C/N ratio was decreased to 2.5, the nitrogen and phosphorus removal performance of the system decreased. The PRA and SNED efficiencies were only 1.36 mg·L-1 and 10%, respectively. During the stable phase of the system (C/N ratio were 10, 7.5 and 5), SNED efficiency reached to 85.9%, with the average effluent concentration of NH4+-N, x--N, and PO43--P being 0.0, 8.1, and 0.1 mg·L-1, respectively.

Injectable hydrogel encapsulating Cu2MnS2 nanoplates for photothermal therapy against breast cancer.

BACKGROUND: In order to explore the possibility of treating breast cancer by local photo-therapy, a photothermal agents loaded in situ hydrogel was established. In detail, The Cu2MnS2 nanoplates were prepared by one-pot synthesis and, the thermosensitive Pluronic F127 was used as the hydrogel matrix. The Cu2MnS2 nanoplates and the hydrogel were characterized by morphous, particle size, serum stability, photothermal performance upon repeated 808 nm laser irradiation as well as the rheology features. The therapeutic effects of the Cu2MnS2 nanoplates and the hydrogel were evaluated qualitatively and quantitatively in 4T1 mouse breast cancer cells. The retention, photothermal efficacy, therapeutic effects and systemic toxicity of the hydrogel were assessed in tumor bearing mouse model. RESULTS: The Cu2MnS2 nanoplates with a diameter of about 35 nm exhibited satisfying serum stability, photo-heat conversion ability and repeated laser exposure stability. The hydrogel encapsulation did not negatively influence the above features of the photothermal agent. The nanoplates loaded in situ hydrogel shows a phase transition at body temperature and, as a result, a long retention in vivo. CONCLUSIONS: The photothermal agent embedded hydrogel played a promising photothermal therapeutic effects in tumor bearing mouse model with low systemic toxicity after peritumoral administration.

Yolk-structured multifunctional up-conversion nanoparticles for synergistic photodynamic-sonodynamic antibacterial resistance therapy.

The worldwide increase in bacterial antibiotic resistance has led to a search for alternative antibacterial therapies. The present study reports the development of yolk-structured multifunctional up-conversion nanoparticles (UCNPs) that combine photodynamic and sonodynamic therapy for effective killing of antibiotic-resistant bacteria. The multifunctional nanoparticles (NPs) were achieved by enclosing hematoporphyrin monomethyl ether (HMME) into its yolk-structured up-conversion core and covalently linked rose bengal (RB) on its silica (SiO2) shell. Excitation of UCNPs with near-infrared (NIR) light that has improved penetration depth for photodynamic therapy (PDT) enabled the activation of HMME and RB and thus the generation of singlet oxygen (1O2). The SiO2 layer, which improved the biocompatibility of the UCNPs, surrounded the yolk structure, with a cavity space which had a high efficiency of loading photosensitizers. Synergistic PDT and sonodynamic therapy (SDT) improved the photosensitizer utilization rate. As a result, a greater inhibition rate was observed when antibiotic-resistant bacteria were treated with a combined therapy (100%) compared with either the PDT (74.2%) or SDT (70%) alone. Our data indicate that the multifunctional NPs developed in this study have the potential for use in the clinical synergistic PDT-SDT treatment of infectious diseases caused by antibiotic-resistant bacteria.

Correlation between the combination of apparent integrated backscatter-spectral centroid shift and bone mineral density.

PURPOSE: To introduce a new diagnostic parameter: the linear combination of apparent integrated backscatter and spectral centroid shift. METHODS: Ultrasonic backscatter measurements were performed at the calcanei of 1262 volunteers in vivo. The hip and spine bone mineral densities of the volunteers were measured using dual X-ray absorptiometry. The apparent integrated backscatter and spectral centroid shift were calculated. A new diagnostic parameter, i.e., the linear combination of apparent integrated backscatter and spectral centroid shift, was introduced and its correlation to bone mineral density was analyzed. RESULTS: The results show that the combination of apparent integrated backscatter and spectral centroid shift is significantly correlated to bone mineral density (R = 0.73-0.84, n = 1262, p < 0.05), and that this correlation is more significant than the correlation between the apparent integrated backscatter and bone mineral density or the correlation between spectral centroid shift and bone mineral density (R = 0.48-0.69, p < 0.05). CONCLUSION: The combination of apparent integrated backscatter and spectral centroid shift can provide the complementary information of attenuation of the two parameters and predict more information about cancellous bone, and may be employed to assess cancellous bone status.

Resveratrol-4-O-D-(2'-galloyl)-glucopyranoside isolated from Polygonum cuspidatum exhibits anti-hepatocellular carcinoma viability by inducing apoptosis via the JNK and ERK pathway.

Resveratrol-4-O-D-(2'-galloyl)-glucopyranoside (RESG) is one of the active compounds isolated from Polygonum cuspidatum. The purpose of our present study was to investigate the anti-hepatocellular carcinoma effect of RESG in vitro and in vivo, and the possible mechanisms in vitro. In vitro, our results showed that RESG could significantly inhibit the human hepatocellular carcinoma viability in the MTT assay, in a dose- and time-dependent manner. Furthermore, our results demonstrated that RESG could induce SMMC-7721 cell apoptosis and activate caspases 3 and caspases 9 by using Annexin V-FITC staining and western blot, respectively. In vivo, RESG also showed efficacy in SMMC-7721 xenograft model in nude mice, and further molecule mechanisms were investigated in vitro. The results showed that RESG up-regulated the p-JNK expressions, whereas it down-regulated the p-ERK expressions. Above results demonstrated that RESG is a potential therapeutic agent for hepatocellular carcinoma via JNK and ERK pathway to induce apoptosis. Our finding provided a basis for further development of RESG as an anticancer agent.

Evaluation of actual vs expected photodynamic therapy spot size.

PURPOSE: To determine the accuracy of the photodynamic therapy (PDT) laser spot size on the retina as generated by 2 Food and Drug Administration (FDA)-approved lasers. DESIGN: Prospective observational case series. METHODS: Fundus photographs were taken of 1 eye of each of 10 subjects with the WinStation 4000 fundus photography system (OIS; Ophthalmic Imaging Systems, Sacramento, California, USA); disc size was calculated using OIS software. Slit-lamp photographs were taken of the PDT laser spot focused on the retina adjacent to the optic disc, using various spot sizes in combination with 3 different contact lenses and 2 different lasers. Spot size at the retina was determined by measuring the ratio of disc diameter to spot diameter in Adobe Photoshop (San Jose, California, USA) and applying this ratio to the OIS disc measurements. RESULTS: Spot size at the retina averaged 87% of expected spot size for the Coherent Opal laser (Coherent Inc, Santa Clara, California, USA) and 104% of expected spot size for the Zeiss Visulas laser (Carl Zeiss Meditec Inc, Dublin, California, USA)(P = .002). Multivariate analysis demonstrated that percentage of expected spot size decreased with larger spot diameter (P = .01 for Coherent laser; P = .02 for Zeiss laser). CONCLUSIONS: PDT spot size at the retina appears to be consistently smaller than expected for the Coherent laser while the spot size was consistently within 10% of expected size for the Zeiss laser. The deviation from expected size increased with larger spot size using the Coherent laser.

Determination of brazilein in rat plasma after intravenous administration by HPLC.

Quantification of brazilein in rat plasma following intravenous administration was achieved by reversed-phase high-performance liquid chromatography using a mobile phase of acetonitrile-0.05 m potassium dihydrogen phosphate water (containing 0.5% triethylamine, pH 3.0; 20:80 v/v) and UV detection at 445 nm. The method was linear (determination coefficient, r(2) = 0.9992) within the tested range (0.313-5.0 microg/mL). Intra- and inter-day precision coefficients of variation and accuracy bias were acceptable (maximal CV value was 2.06% for intra-day and 1.71% for inter-day) over the entire range. The recoveries were 81.48, 84.61 and 82.83% for concentrations of 0.313, 1.25 and 5.0 microg/mL, respectively. The concentration-time curve of brazilein after intravenous administration was fitted to the two-compartment model. This is the first time that brazilein in rat plasma was detected by HPLC-UV method and its pharmacokinetic characteristic was comprehensively studied.