Treatment of telangiectasias with a 595-nm pulsed dye laser following hemangioma involution: a retrospective analysis.

Telangiectasias are the most frequent type of sequelae of infantile hemangiomas after involution. Few studies have reported the treatment of telangiectasias with 595-nm pulsed dye lasers. Therefore, the objective of this study was to assess the efficacy and safety of a 595-nm pulsed dye laser for treating residual telangiectasias following hemangioma involution. This is a retrospective case series that analyzes the medical records and reviews the charts of 22 patients who had undergone 595-nm pulsed dye laser treatment for residual telangiectasias. Pre- and post-treatment digital images were independently assessed, and the changes were scored to ascertain the efficacy of the treatment (0 = no change, 4 = complete improvement). Of the 22 patients, 59.1% experienced complete resolution of telangiectasias following treatment. No serious complications or side effects were reported. The observations indicate that the 595-nm pulsed dye laser is effective and safe for treating residual telangiectasias following hemangioma involution.

A new abietane diterpenoid from Lycopodium complanatum.

A new abietane diterpenoid, 1ß, 11-epoxyabieta-12-hydroxy-8, 11, 13-triene-7-one (1), along with three known compounds (2-4), was isolated from Lycopodium complanatum. Their structures were confirmed by the analysis of 1D, 2D NMR and HRESIMS data, and comparison with previous spectral data. All compounds were tested for inhibitory activities against A549, HepG2 and MCF-7 tumor cell lines. [Figure: see text].

Treatment of pyogenic granuloma in children with a 595 nm pulsed dye laser: A retrospective study of 212 patients.

BACKGROUND: Pyogenic granuloma (PG) is a common vascular neoplasm in children. Data on 595 nm pulsed dye lasers for the treatment of PG in children remain scarce. OBJECTIVE: To summarize the clinical characteristics and to evaluate the effectiveness and safety of the 595 nm pulsed dye laser for the treatment of PG in children. STUDY DESIGN: Retrospective case series. METHODS: A retrospective study was performed on 212 patients treated for PG with a 595 nm pulsed dye laser. SPSS version 19.0 was used for statistical analysis. RESULTS: Among all 212 patients treated, 208 showed complete resolution of the lesion, and 4 dropped out after one treatment due to bleeding. A single treatment was sufficient in 139 (66.8%) patients, while two or three treatments were sufficient in 69 (33.2%) patients. Male patients responded better than female patients (χ2 = 7.603, p =0.006). Lesions in the nonorbital region responded better than those in the orbital region (χ2 = 7.445, p =0.006). The size of the lesion affected the effectiveness, and lesions with smaller diameters (t = -5.776, p <0.01) and heights (t = -10.368, p <0.01) showed better results. COMPLICATIONS AND SIDE EFFECTS: Twelve patients (5.8%) were reported to have local complications and side effects, including edematous erythema, slight bleeding, hyperpigmentation, and hypopigmentation. The edematous erythema and slight bleeding disappeared gradually after several days. The localized pigment changes usually resolved spontaneously and disappeared completely after 6 months. CONCLUSIONS: Our experience confirmed the efficacy and safety of the 595 nm pulsed dye laser for the treatment of PG in children.

Two New C21 Steroidal Glycosides from Selaginella Braunii Baker.

Two new C21 steroidal glycosides, brapreguanes A and B (1-2) were isolated from 75 % aqueous ethanol extract of Selaginella braunii Baker. Their structures were established by spectroscopic analyses (1D/2D NMR spectra and HR-ESI-MS). The absolute configurations of sugar were elucidated by enzymatic hydrolysis and GCMS analysis. In addition, all compounds were evaluated for the anti-proliferative activities against various human cancer cells in vitro. Compounds exhibited no inhibition to various human cancer cells.

[Nur77 inhibits the proliferation of prostate cancer cells].

OBJECTIVE: To study the effects of Nur77 on prostate cancer (PCa) cell growth and its potential value in the treatment of PCa. METHODS: We detected the expression of the NUR77 protein in human PCa tissues and cells by Western blot and determined the effects of Nur77 on the proliferation and apoptosis of the PCa cells by flow cytometry. RESULTS: Nur77 and AR were expressed in the human PCa tissue and cells, and overexpressed NUR77 inhibited the proliferation and cell cycle progression of the PCa LNCaP cells. The small-molecule receptor agonists cytosporone B and DIMC of Nur7 significantly suppressed the growth and induced the apoptosis of the PCa LNCaP cells. CONCLUSIONS: Nur77 inhibits the proliferation and induces the apoptosis of PCa cells, and is expected to be a potential molecular target for the treatment of PCa.

New prenylflavonol glycosides with xanthine oxidase inhibitory activity from the leaves of Cyclocarya paliurus.

Eight new prenylflavonol glycosides (1-8), along with five known analogues (9-13) were isolated from the n-butanol extract of the dried leaves of Cyclocarya paliurus (family Juglandaceae) for the first time. The structures of these compounds were characterized by comprehensive analysis of 1D, 2D NMR, HRESIMS, UV data and acid hydrolysis. In bioassay, all these thirteen prenylflavonol glycosides exhibited inhibitory effects on xanthine oxidase (XOD) activity. Especially compounds 2 and 7, showed outstanding IC50 values of 31.81 ± 2.20 and 29.71 ± 3.69 µM, respectively.

IL-25 protects against high-fat diet-induced hepatic steatosis in mice by inducing IL-25 and M2a macrophage production.

Interleukin (IL)-25 is a cytokine that has previously been shown to have a protective role against nonalcoholic fatty liver disease (NAFLD), which is associated with the induction of M2 macrophage differentiation. However, the direct relationships between IL-25 expression regulation, M2 induction and NAFLD remain unknown. In this study, we demonstrate that IL-25 promotes hepatic macrophage differentiation into M2a macrophages both in vivo and in vitro via the IL-13/STAT6 pathway. M2 macrophages that were differentiated in vitro were able to ameliorate high-fat diet HFD-induced hepatic steatosis. Furthermore, we found that IL-25 treatment, both in vitro and in vivo, promotes direct binding of STAT6 to the IL-25 gene promoter region. This binding of STAT6 in response to IL-25 treatment also resulted in the increase of IL-25 expression in hepatocytes. Together, these findings identify IL-25 as a protective factor against HFD-induced hepatic steatosis by inducing an increase of IL-25 expression in hepatocytes and through promotion of M2a macrophage production.

An Ammonium-Formate-Driven Trienzymatic Cascade for ω-Transaminase-Catalyzed (R)-Selective Amination.

(R)-Amination mediated by (R)-specific ω-transaminases generally requires costly d-alanine in excess to obtain the desired chiral amines in high yield. Herein, a one-pot, trienzymatic cascade comprising an (R)-specific ω-transaminase, an amine dehydrogenase, and a formate dehydrogenase was developed for the economical and eco-friendly synthesis of (R)-chiral amines. Using inexpensive ammonium formate as the sole sacrificial agent, the established cascade system enabled efficient ω-transaminase-mediated (R)-amination of various ketones, with high conversions and excellent ee (>99%); water and CO2 were the only waste products.

The C-Reactive Protein/Albumin Ratio as a Predictor of Mortality in Patients with HBV-Related Decompensated Cirrhosis.

BACKGROUND: The C-reactive protein to albumin ratio (CAR) is a novel inflammation index that has recently been used as a marker for poor prognosis or mortality in various patient groups. This study aimed to evaluate the association between the CAR and 30-day mortality in patients with hepatitis B virus-related decompensated cirrhosis (HBV-DeCi). METHODS: This was a retrospective cohort study of 113 patients who had been diagnosed with HBV-DeCi. Univariate and multivariate regression models were used to determine risk factors for mortality. RESULTS: The CAR was observed to be significantly higher in the non-surviving patients compared to the surviving patients. Moreover, the CAR was positively correlated with the model for end-stage liver disease (MELD) score and Child-Pugh score. In multivariate analysis, the CAR and the MELD score were independent prognostic factors for HBV-DeCi patients. CONCLUSIONS: A high CAR value at admission can serve as an independent predictor of 1-month mortality in patients with HBV-DeCi.

Image-guided vibrometry system integrated with spectral- and time-domain optical coherence tomography.

Vibrometry using optical coherence tomography (OCT) can provide valuable information for investigating either the mechanical properties or the physiological function of biological tissues, especially the hearing organs. Real-time imaging of the measured tissues provides structure imaging and spatial guidance for and is thus highly demanded by such vibrometry. However, the traditional time-domain OCT (TD-OCT) systems, although capable of subnanometric vibrometry at large ranges of frequencies, are unable to offer an imaging speed that is high enough to acquire depth-resolved images for guidance. The spectral-domain OCT (SD-OCT) systems, although allowing image-guided vibrometry, are challenged in measuring vibration at high frequencies, particularly for scattering tissue specimens that require longer exposure time to ensure imaging and vibrometry performance. This is because of their limit in the line-scan rate of the CCD, in which the maximum resolvable frequency measured by the SD-OCT is about 1/4 of the CCD line-scan rate in practice. In the present study, we have developed a dual-mode OCT system combining both SD-OCT and TD-OCT modalities for image-guided vibrometry, as the SD-OCT can provide guiding structural images in real-time and, moreover, the TD-OCT can guarantee vibrometry at large ranges of frequencies, including high frequencies. The efficacy of the developed system in image-guided vibrometry has been experimentally demonstrated using both piezoelectric ceramic transducer (PZT) and ex vivo middle-ear samples from guinea pigs. For the vibrometry of PZT, the minimum detectable vibration amplitude was reached at ∼0.01 nm. For the vibrometry of the sound-evoked biological samples, both real-time two-dimensional imaging and subnanometric vibrometry were performed at the frequency ranging from 1 to 40 kHz. These results indicate that our dual-mode OCT system is able to act as an excellent vibrometer enabling image-guided high-frequency measurement.

Relationship Between Modic Changes and Sagittal Balance Parameters in the Cervical Spine.

BACKGROUND We explored the possible relationship between Modic changes (MCs) and sagittal parameters of the cervical spine. MATERIAL AND METHODS We enrolled 150 patients with cervical MC on the magnetic resonance imaging (MRI) scans in the MC (+) group and divided them into 3 sub-groups with 50 patients each: the MC1 sub-group, the MC2 sub-group, and the MC3 sub-group. Another 150 healthy subjects receiving routine health examinations were also enrolled in the study as the MC (-) group. The sagittal parameters in the cervical spine were measured and compared and multiple logistic regression analysis was performed to analyze the risk factor for the occurrence of MC. RESULTS Four cervical sagittal parameters were measured and compared between all the enrolled groups, including neck tilt (NT), T1 slope (T1s), thoracic inlet angle (TIA), and Cobb C2-C7. The results confirmed that the parameter of Cobb C2-C7 was much smaller in the MC(+) group when compared with that in the MC(-) group (P<0.05), while no significant differences were detected between the MC(+) and MC(-) groups for the parameters of NT, T1 T1s, and TIA (P>0.05). Multiple logistic regression analysis showed that Cobb C2-C7 (less than 8.5°) could be regarded as the risk factor for the occurrence of MC, and the receiver operating characteristic (ROC) curve showed that moderate diagnostic significance was obtained with an area under curve (AUC) of 0.82. CONCLUSIONS The present study demonstrated that Cobb C2-C7 (less than 8.5°) is a potential risk factor for the development of MC.

Negative Pressure Therapy in the Regeneration of the Sciatic Nerve Using Vacuum - Assisted Closure in a Rabbit Model.

BACKGROUND The aim of this study was to investigate the effects of negative pressure therapy in the regeneration of the rabbit sciatic nerve using vacuum assisted closure (VAC). MATERIAL AND METHODS Thirty male New Zealand white rabbits underwent surgical injury of the sciatic nerve, followed by negative pressure therapy using vacuum assisted closure (VAC), in three treatment groups: Group A: 0 kPa; Group B: -20 kPa; Group C: -40 kPa. At 12 weeks following surgery, the following factors were studied: motor nerve conduction velocity (MNCV); the number of myelinated nerve fibers; the wet weight of the gastrocnemius muscle. Gastrocnemius muscle and sciatic nerve tissue samples were studied for the expression of S100, and brain-derived neurotrophic factor (BDNF) using Western blot. RESULTS At 12 weeks following VAC treatment, the MNCV, number of myelinated nerve fibers, and wet weight of the gastrocnemius muscle showed significant differences between the groups (p<0.05), in the following order: Group B >Group A >Group C. The sciatic nerve at 12 weeks following VAC in Group B and Group C showed a significant increase in expression of S100 and BDNF when compared with Group A; no significant differences were detected between Group B and Group C results from Western blot at 12 weeks. CONCLUSIONS The findings of this study, using negative pressure therapy in VAC in a rabbit model of sciatic nerve damage, have shown that moderate negative pressure was beneficial, but high values did not benefit sciatic nerve repair.

A Fluidic Biosensor Based on a Phase-Sensitive Low-Coherence Spectral-Domain Interferometer.

A phase-sensitive fluidic biosensor based on a spectral-domain low-coherence interferometer is presented in this paper. With a fiber optic probe employing the common-path interferometric configuration, subnanometric changes in thickness of the molecular layers can be detected through phase analysis of the acquired interference signal from the sensor surface. Advantages of this biosensor include its picometer-scale thickness sensitivity, 13.9-ms time response, and tolerance to the fluctuation in concentration of the target solution. The capabilities of this biosensor in monitoring specific molecular binding and recognizing specific molecular was successfully demonstrated by using the reactions between the molecules of protein A and IgG. The calculated minimum detectable concentration of IgG is 0.11 µg/mL.

High-resolution study of the 3D collagen fibrillary matrix of Achilles tendons without tissue labelling and dehydrating.

Knowledge of the collagen structure of an Achilles tendon is critical to comprehend the physiology, biomechanics, homeostasis and remodelling of the tissue. Despite intensive studies, there are still uncertainties regarding the microstructure. The majority of studies have examined the longitudinally arranged collagen fibrils as they are primarily attributed to the principal tensile strength of the tendon. Few studies have considered the structural integrity of the entire three-dimensional (3D) collagen meshwork, and how the longitudinal collagen fibrils are integrated as a strong unit in a 3D domain to provide the tendons with the essential tensile properties. Using second harmonic generation imaging, a 3D imaging technique was developed and used to study the 3D collagen matrix in the midportion of Achilles tendons without tissue labelling and dehydration. Therefore, the 3D collagen structure is presented in a condition closely representative of the in vivo status. Atomic force microscopy studies have confirmed that second harmonic generation reveals the internal collagen matrix of tendons in 3D at a fibril level. Achilles tendons primarily contain longitudinal collagen fibrils that braid spatially into a dense rope-like collagen meshwork and are encapsulated or wound tightly by the oblique collagen fibrils emanating from the epitenon region. The arrangement of the collagen fibrils provides the longitudinal fibrils with essential structural integrity and endows the tendon with the unique mechanical function for withstanding tensile stresses. A novel 3D microscopic method has been developed to examine the 3D collagen microstructure of tendons without tissue dehydrating and labelling. The study also provides new knowledge about the collagen microstructure in an Achilles tendon, which enables understanding of the function of the tissue. The knowledge may be important for applying surgical and tissue engineering techniques to tendon reconstruction.

Electroconvulsive Therapy Under General Anesthesia With Cisatracurium, Laryngeal Mask Airways, and Bispectral Index.

OBJECTIVES: Electroconvulsive therapy (ECT) has dramatically reduced musculoskeletal complications when carried out with muscle relaxants under general anesthesia. However, seizure quality can be affected by the depth of anesthesia and choice of anesthetic agent. The purpose of this study was to describe a general anesthetic technique for ECT by using laryngeal mask, bispectral index (BIS), and muscle relaxant monitoring. METHODS: Twenty-one patients, between ages 18 and 70 years (American Society of Anesthesiologists physical status I-III), who underwent a total of 89 sessions of ECT were examined in a retrospective study. Anesthesia was induced by use of propofol (1.0 mg/kg) followed by cisatracurium (0.2 mg/kg). The BIS, train-of-four, and end-tidal carbon dioxide were all monitored continuously. A laryngeal mask airway was used to maintain and protect the airway during the procedure. Electroconvulsive therapy stimuli were applied bilaterally when the train-of-four was assessed as being zero and BIS scores were 70. All patients then received 5 µg sufentanil and 2 mg midazolam, while titrated to maintain the BIS value at 40 to 50, before the muscle relaxation exhibited complete recovery. RESULTS: The mean duration of treatment process takes approximately 82.5 minutes. Mean (SD) seizure length was 58.8 (28.3) seconds, with 4.5% incidence of restimulation per treatment. Incidence of awareness was 0%. No patients exhibited delirium, nausea, vomiting, or myalgia in the postseizure phase. CONCLUSIONS: Bispectral index monitoring of the depth of anesthesia may have improved seizure quality, and awareness did not occur.

An improved flurogenic probe for high-throughput screening of 2-deoxyribose aldolases.

2-Deoxyribose aldolase-catalyzed C-C bond-forming reactions have become 1 more and more important in synthesis of statins and other drug intermediates. Many methods have focused on improving the aldolase properties and harvesting new aldolases, but a good outcome depends on the efficiency of the high-throughput screening system. We have developed a visible green fluorescence probe based on a coumarin derivative, which can be reversibly modulated by a retro-aldol reaction catalyzed by 2-deoxyribose aldolase for selecting aldolase mutants with high activity. This assay system provides a convenient and effective way for high-throughput screening aldolases as the green fluorescence is sensitively detected and daylight-viewable without the need for specialist equipment. We used our probe to successfully harvest aldolase mutants with higher activities than the parent from a random mutagenesis library.

Highly efficient enzymatic synthesis of tert-butyl (S)-6-chloro-5-hydroxy-3-oxohexanoate with a mutant alcohol dehydrogenase of Lactobacillus kefir.

tert-Butyl (S)-6-chloro-5-hydroxy-3-oxohexanoate ((S)-CHOH) is a valuable chiral synthon, which is used for the synthesis of the cholesterol-lowering drugs atorvastatin and rosuvastatin. To date, only the alcohol dehydrogenases from Lactobacillus brevis (LbADH) and Lactobacillus kefir (LkADH) have demonstrated catalytic activity toward the asymmetric reduction of tert-butyl 6-chloro-3,5-dioxohexanoate (CDOH) to (S)-CHOH. Herein, a tetrad mutant of LkADH (LkTADH), A94T/F147L/L199H/A202L, was screened to be more efficient in this bioreduction process, exhibiting a 3.7- and 42-fold improvement in specific activity toward CDOH (1.27 U/mg) over LbADH (0.34 U/mg) and wild-type LkADH (0.03 U/mg), respectively. The molecular basis for the improved catalytic activity of LkTADH toward CDOH was investigated using homology modeling and docking analysis. Two major issues had a significant impact on the biocatalytic efficiency of this process, including (i) the poor aqueous stability of the substrate and (ii) partial substrate inhibition. A fed-batch strategy was successfully developed to address these issues and maintain a suitably low substrate concentration throughout the entire process. Several other parameters were also optimized, including the pH, temperature, NADP(+) concentration and cell loading. A final CDOH concentration of 427 mM (100 g/L) gave (S)-CHOH in 94 % yield and 99.5 % e.e. after a reaction time of 38 h with whole cells expressing LkTADH. The space-time yield and turnover number of NADP(+) in this process were 10.6 mmol/L/h and 16,060 mol/mol, respectively, which were the highest values ever reported. This new approach therefore represents a promising alternative for the efficient synthesis of (S)-CHOH.

Introducing a salt bridge into the lipase of Stenotrophomonas maltophilia results in a very large increase in thermal stability.

High thermostability of enzymes is a prerequisite for their biotechnological applications. An organic solvent-tolerant and cold-active lipase, from the Stenotrophomonas maltophilia, was unstable above 40 °C in previous studies. To increase the enzyme stability, possible hydrogen-bond networks were simulated by the introduction of a salt bridge in a highly flexible region of the protein. Compared with the wild-type lipase, a mutant lipase (G165D and F73R) showed a >900-fold improvement in half-life at 50 °C, with the optimal activity-temperature increasing from 35 to 90 °C. Therefore, the hydrogen-bond strategy is a powerful approach for improving enzyme stability through the introduction of a salt bridge.

Modification and simulation of Rhizomucor miehei lipase: the influence of surficial electrostatic interaction on enantioselectivity.

Surface residues have a significant impact on the enantioselectivity of lipases. But the molecular basis of this has never been explained. In this work, transition state complexes of Rhizomucor miehei lipase (RmL) and (R)- or (S)-n-butyl 2-phenxypropinate were studied using molecular dynamics. According to comparison between B-factor of the two simulated complexes, the ß 1-ß 2 loop and α 2 helix were considered the enantioselectivity-determining domains of RmL. Interaction analysis of these domains suggested an Asp(61)-Arg(86) electrostatic interaction linking the loop and helix strongly impacting enantioselectivity of RmL. Modification of Arg(86) by 1, 2-cyclohexanedione weakening this interaction decreased the E ratio from 6 to 1, modification by 1-iodo-2, 3-butanedione covalently bonding Asp(61) and Arg(86) strengthening the interaction increased the E ratio to 45. Dynamics simulation and energy calculation of the modified lipases also displayed corresponding decreases or increases of enantioselectivity.

Identification and significance of mobilized endothelial progenitor cells in tumor neovascularization of renal cell carcinoma.

Neovascularization is a key role of renal cell carcinoma (RCC) and the status of neovascularization in RCC is closely correlated with the tumor development and patient prognosis. Endothelial progenitor cells (EPCs) are considered as important building blocks for neovascularization. However, the role of mobilized EPCs in RCC remains unknown. In this study, the orthotopic RCC model was established to investigate the distribution, frequency, and significance of mobilized EPCs. We found that circulating endothelial progenitor cell (CEPC) levels and plasma angiogenic factors (vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1 (SDF-1) were higher in peripheral blood (PB) of the RCC than those in the normal group and positively correlated with each other. EPC levels in adjacent nonmalignant kidney tissue (AT) were significantly higher than those in tumor tissue (TT) and normal kidney tissue (NT), which were positively correlated with CEPC levels. VEGF, VEGF receptor-2 (Flk), and SDF-1 and its SDF-1 receptor (CXCR4) expression in AT was significantly higher than that in TT and NT. Levels of these angiogenic factors in AT were positively correlated with those in PB. Mean microvessel density (MVD) was higher in AT than in TT, and that in TT was slightly lower than that in NT. Our findings propose that mobilized EPCs play an important role in RCC neovascularization. EPCs in PB and AT can be used as a biomarker for predicting RCC progression.