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Purpose: Sodium taurocholate cotransporting polypeptide (NTCP) is a transmembrane protein responsible for delivering indocyanine green (ICG), an ideal infrared fluorescent dye, from extracellular space into the cytoplasm. Additionally, NTCP located in the hepatocyte membrane is the portal for hepatitis B and D virus (HBV/HDV) infections. This study verified the feasibility of NTCP as a reporter and further established a drug-screening platform for HBV/HDV infections.Procedures: NTCP was transduced into HT-29, a colorectal cancer cell line. To examine the use of NTCP as a reporter, NTCP-expressing cells were treated with ICG and examined through flow cytometry, an in vivo imaging system (IVIS), and confocal microscopy. Furthermore, ICG was administrated to NTCP-expressing tumor-bearing nude mice and examined using the IVIS. To study the drug-screening platform, NTCP-expressing cells were treated with cyclosporin A, an NTCP inhibitor, and ICG, and examined using a multimode detection platform. Moreover, nude mice were injected with NTCP inhibitors and ICG, and subsequently, their ICG signal was examined in vivo and in the blood.Results: In the reporter study, the ICG signal was higher in NTCP-expressing cells/tumors than in control cells/tumors after ICG treatment. In the drug-screening platform study, NTCP-expressing cells had decreased ICG intensity after treatment with NTCP inhibitors and ICG. Nude mice that were administered cyclosporin A had lower ICG intensity in the liver and higher intensity in the peripheral tissue and blood.Conclusions: NTCP and ICG form an ideal reporter system with extensive applications in cancer biology, robust drug-drug interactions, and drug screening in HBV/HDV infections. [ABSTRACT FROM AUTHOR]

Acute post-operative pain can remain untreated if patients cannot express themselves. The perfusion index (PI) may decrease when pain activates sympathetic tone and may increase after analgesics are administered. We evaluated if the perfusion index is a feasible indicator for objectively assessing pain relief in the postanesthesia care unit (PACU) and calculated the changes in PI measurements at the time of discharge from the PACU relative to baseline PI measurements to examine if the PI is a useful criterion for discharging patients from the postanesthesia care unit. This retrospective observational study enrolled female patients who were admitted for gynecological or general surgery. The patients received general anesthesia and were admitted to the postanesthesia care unit. The PI, visual analogue scale (VAS) score, heart rate, and blood pressure were recorded before and after administration of intravenous morphine. Changes in these parameters before and after analgesics were administered and the difference of these parameters between age and BMI subgroups were compared. The correlation between the PI and VAS score, ΔPI and ΔVAS, and %ΔPI and %ΔVAS were also evaluated. The percentage change in ΔPI (P9-T0/T0) of the patients at the time of discharge from the postanesthesia care unit relative to baseline PI measurements was calculated. Eighty patients were enrolled, and there were 123 instances during which analgesia was required. Heart rate, PI, and VAS score were significantly different before and after analgesics were administered (p < 0.0001). The difference of parameters between age and BMI subgroups were not significant. The correlation between the PI and VAS score, ΔPI and ΔVAS, and the percentage change in ΔPI and ΔVAS showed weak correlations in age, BMI subgroups, and all measurements. The baseline PI and the PI when arriving at and when being discharged from the postanesthesia care unit were significantly different (p < 0.01). The mean percentage change in Δ PI at the time of discharge from the PACU was 66.2%, and the 99% confidence interval was 12.2%~120.3%. The perfusion index was increased, and the VAS score was decreased significantly after analgesics were administered, but the correlation was weak in each subgroup. The VAS score is a subjective and psychometric parameter. The PI increased when partial pain relief was achieved after morphine was administered but did not reflect pain intensity or changes in the VAS score regardless of age or BMI. A percentage change in ΔPI at the time of discharge from the PACU relative to baseline PI measurements of greater than 12% can be used as a supplemental objective discharge criterion for pain assessment in the postanesthesia care unit. [ABSTRACT FROM AUTHOR]

The ethanolic extract of Aloe barbadensis Miller leaf skin showed inhibitory activity against phosphodiesterase-4D (PDE4D), which is a therapeutic target of inflammatory disease. Subsequent bioassay-guided fractionation led to the isolation of two new anthrones, 6′- O -acetyl-aloin B ( 9 ) and 6′- O -acetyl-aloin A ( 11 ), one new chromone, aloeresin K ( 8 ), together with thirteen known compounds. Their chemical structures were elucidated by spectroscopic methods including UV, IR, 1D and 2D NMR, and HRMS. All of the isolates were screened for their inhibitory activity against PDE4D using tritium-labeled adenosine 3′,5′-cyclic monophosphate ( 3 H-cAMP) as substrate. Compounds 13 and 14 were identified as PDE4D inhibitors, with their IC 50 values of 9.25 and 4.42 μM, respectively. These achievements can provide evidences for the use of A. barbadensis leaf skin as functional feed additives for anti-inflammatory purpose. [ABSTRACT FROM AUTHOR]

Endo‐microscopy is crucial for real‐time 3D visualization of internal tissues and subcellular structures. Conventional methods rely on axial movement of optical components for precise focus adjustment, limiting miniaturization and complicating procedures. Meta‐device, composed of artificial nanostructures, is an emerging optical flat device that can freely manipulate the phase and amplitude of light. Here, an intelligent fluorescence endo‐microscope is developed based on varifocal meta‐lens and deep learning (DL). The breakthrough enables in vivo 3D imaging of mouse brains, where varifocal meta‐lens focal length adjusts through relative rotation angle. The system offers key advantages such as invariant magnification, a large field‐of‐view, and optical sectioning at a maximum focal length tuning range of ≈2 mm with 3 µm lateral resolution. Using a DL network, image acquisition time and system complexity are significantly reduced, and in vivo high‐resolution brain images of detailed vessels and surrounding perivascular space are clearly observed within 0.1 s (≈50 times faster). The approach will benefit various surgical procedures, such as gastrointestinal biopsies, neural imaging, brain surgery, etc. [ABSTRACT FROM AUTHOR]

Abstract: Bioassay-guided fractionation of the ethanol extract of the Chinese folk medicine Crotalaria ferruginea led to the isolation of a new isoflavonoid, 4′-hydroxy-2′-methylalpinum-isoflavone (1), and eight known analogs (2–9). Their structures were elucidated by spectroscopic analysis. Compounds 1, 2, 5, and 8 showed inhibitory activities against phosphodiesterase-4 (PDE4), a therapeutic target of asthma, with IC50 values ranging from 2.57 to 8.94μM. The possible action mechanism and the structure–activity relationship (SAR) of the active isoflavonoids were explored by using molecular docking and molecular dynamics (MD) simulation methods. Our study herein may explain the anti-inflammatory function of this plant in Chinese folk medicine. [Copyright &y& Elsevier]

Abstract: Surface plasmon resonance (SPR) can detect molecules bound to a surface by subtle changes in the SPR angle. By immobilizing probes onto the surface and passing analyte solution through the surface, changes in SPR angle indicate the binding between analyte and probes. Detection of analyte from solution can be achieved easily. By using rolling circle amplification (RCA) and nanogold-modified tags, the signals of analyte binding are greatly amplified, and the sensitivity of this technique is significantly improved. Furthermore, this technique has potentials for ultra-sensitive detection and microarray analysis. In this paper, this detection technique is introduced and shown to have great amplification capability. Using 5nm nanogold with 30min of RCA development time, this proposed protein detection technique shows over 60 times amplification of the original signal. [Copyright &y& Elsevier]

Abstract: Growing attention has been given to the potential of a pulmonary route as a non-invasive administration for systemic delivery of therapeutic agents (mainly peptides and proteins). The lungs provide a large absorptive surface area, extremely thin absorptive mucosal membrane, and good blood supply. The non-invasive nature of this pathway makes it especially valuable for the delivery of large molecular protein. However, pulmonary delivery of peptides and proteins is complicated by the complexity of the anatomic structure of the human respiratory system and the effect of disposition exerted by the respiration process. In this study, novel nebulizer-compatible liposomal carrier for aerosol pulmonary drug delivery of insulin was developed and characterized. Experimental results showed that insulin could be efficiently encapsulated into liposomes by preformed vesicles and detergent dialyzing method. The optimal encapsulation efficiency was achieved when 40% ethanol was used. The particle size of liposomal aerosols from ultrasonic nebulizer approximated to 1 μm. Insulin was stable in the liposomal solution. Animal studies showed that plasma glucose level was effectively reduced when liposomal insulin was delivered by inhalation route of using aerosolized insulin-encapsulated liposomes. Including fluorescent probe (phosphatidylethanolamine-rhodamine) into liposome, we found that the liposomal carriers were effectively and homogeneously distributed in the lung aveolar. Liposome-mediated pulmonary drug delivery promotes an increase in drug retention-time in the lungs, and more importantly, a reduction in extrapulmonary side-effects which invariably results in enhanced therapeutic efficacies. [Copyright &y& Elsevier]

Developing a readily available biosensor with excellent performances is the main focus of many research groups. Recently, major breakthroughs in miniaturization of molecular analysis have produced DNA and protein microarrays. The aim of our group is to develop a sensitive technique for analyzing signals on protein microarray by applying the surface plasmon resonance (SPR) method. This new detection technique for specific molecular binding utilizes rolling circles amplification (RCA) post-signal processing method [Nat. Genet. 19 (1998) 225–232] and optical visualization by nanogold particle-labeled molecules on a micro-structured chip surface. By covalent bonding of the RCA primer to the detection antibody guarantees that the linkage between the analyte and the amplified RCA product is maintained during the assay. Experimental results show that RCA has significantly enhanced sensitivity compared to conventional methods. This combination of an easily detectable signal with chip technology should have the potential to become a successful commercial application. [Copyright &y& Elsevier]

This study describes a highly efficient method for encapsulating protein drugs into liposomes without using toxic solvents such as chloroform. Large unilamellar vesicles (LUVs) were formed by the ethanol injection method. The effects of composition of phospholipid, buffer concentration, incubation time, incubation temperature, drug loading, ethanol content, and the presence of poly(ethylene) glycol (PEG) lipids on the entrapment efficiency of protein were investigated. It was shown that these preformed LUVs could be induced to entrap protein drugs in the presence of ethanol. Protein could be efficiently encapsulated into liposomes. The interaction of the liposomes with proteins leads to the formation of multilamellar liposomes ranging in size from 70 to 120 nm, only slightly bigger than the parent LUVs from which they originated. Protein drugs were stable in the liposomal solution. There is no significant activity loss during the encapsulation process. The optimal encapsulation efficiency was achieved when 30% ∼ 40% ethanol was used in encapsulating protein drugs. Due to the steric hindrance, LUVs containing a PEG coating will dramatically reduce the encapsulation efficiency, even in liposomes containing very low amount of PEG. [ABSTRACT FROM AUTHOR]

Purpose: To compare ChatGPT-4 and ChatGPT-3.5's performance on Taiwan urology board examination (TUBE), focusing on answer accuracy, explanation consistency, and uncertainty management tactics to minimize score penalties from incorrect responses across 12 urology domains. Methods: 450 multiple-choice questions from TUBE(2020–2022) were presented to two models. Three urologists assessed correctness and consistency of each response. Accuracy quantifies correct answers; consistency assesses logic and coherence in explanations out of total responses, alongside a penalty reduction experiment with prompt variations. Univariate logistic regression was applied for subgroup comparison. Results: ChatGPT-4 showed strengths in urology, achieved an overall accuracy of 57.8%, with annual accuracies of 64.7% (2020), 58.0% (2021), and 50.7% (2022), significantly surpassing ChatGPT-3.5 (33.8%, OR = 2.68, 95% CI [2.05–3.52]). It could have passed the TUBE written exams if solely based on accuracy but failed in the final score due to penalties. ChatGPT-4 displayed a declining accuracy trend over time. Variability in accuracy across 12 urological domains was noted, with more frequently updated knowledge domains showing lower accuracy (53.2% vs. 62.2%, OR = 0.69, p = 0.05). A high consistency rate of 91.6% in explanations across all domains indicates reliable delivery of coherent and logical information. The simple prompt outperformed strategy-based prompts in accuracy (60% vs. 40%, p = 0.016), highlighting ChatGPT's limitations in its inability to accurately self-assess uncertainty and a tendency towards overconfidence, which may hinder medical decision-making. Conclusions: ChatGPT-4's high accuracy and consistent explanations in urology board examination demonstrate its potential in medical information processing. However, its limitations in self-assessment and overconfidence necessitate caution in its application, especially for inexperienced users. These insights call for ongoing advancements of urology-specific AI tools. [ABSTRACT FROM AUTHOR]

Molecular and cellular imaging in living organisms have ushered in an era of comprehensive understanding of intracellular and intercellular events. Currently, more efforts have been focused on the infrared fluorescent dyes that facilitate deeper tissue visualization. Both sodium taurocholate cotransporting polypeptide (NTCP) and organic-anion-transporting polypeptide 1B3 (OATP1B3) are capable of carrying indocyanine green (ICG) into the cytoplasm. We compared the feasibility of NTCP and OATP1B3 as reporter genes in combination with ICG. NTCP and OATP1B3 were transduced into HT-29 cells. Genetically modified HT-29 cells were inoculated into nude mice. ICG was administered in vitro and in vivo and the signals were observed under confocal microscopy, flow cytometry, multimode microplate reader, and an in vivo imaging system. Both NTCP- and OATP1B3-expressing cells and xenografts had higher ICG intensities. The OATP1B3-expressing xenograft has a higher ICG uptake than the NTCP-expressing xenograft. NTCP or OATP1B3 combined with ICG could serve as a noninvasive imaging modality for molecular and cellular imaging. OATP1B3 outperforms NTCP in terms of in vivo imaging. [ABSTRACT FROM AUTHOR]

Highlights • A novel categorization of Cushing response is proposed: pathological, physiological and negative. • Physiological signals processed by wavelet transform and decision tree establish a predictive model. • The warning system identifies the real-time condition and predicts the outcome. Abstract Objective Cushing response (CR) is categorized. Wavelet transform (WT) and decision tree (DT) are utilized to analyze physiological signals from neurocritical patients. A warning model is built for recognition of CR, real-time evaluation of intracranial condition and prediction of neurological outcome. Methods Physiological signals of neurocritical patients are preprocessed by WT and compressed by linear regression. An algorithm labels each segment as pathological, physiological, negative or uncertain CR. The DT identifies CR. Continuous data input to the established DT predicts condition at that moment and following outcome. Results From 33 neurocritical patients, 422,524 sets of physiological signals were collected. The cross-validation scores of DT ranged from 0.562 to 0.579 with averaged accuracy rate 60.6% (3.5–98.1%). The model correctly predicted the outcome of the training group, 87.9% in accuracy. The ratios of pathological CR were 9.3 ± 16.6%, 74.2 ± 29.7% and 99.7 ± 0.3% in patients of good, coma and death groups, respectively. The prediction accuracy for a test set of 103 patients reached 81.6%. Conclusions Cushing response categorization helps in identifying critical conditions and predicting outcome. Significance A novel concept of four categories of Cushing response is proposed to represent broader ranges of intracranial change. [ABSTRACT FROM AUTHOR]

Background: The spinal hybrid elastic (SHE) rod dynamic stabilization system can provide sufficient spine support and less adjacent segment stress. This study aimed to investigate the biomechanical effects after the internal fracture of SHE rods using finite element analysis.Methods: A three-dimensional nonlinear finite element model was developed. The SHE rod comprises an inner nitinol stick (NS) and an outer polycarbonate urethane (PCU) shell (PS). The fracture was set at the caudal third portion of the NS, where the maximum stress occurred. The resultant intervertebral range of motion (ROM), intervertebral disc stress, facet joint contact force, screw stress, NS stress, and PCU stress were analyzed.Results: When compared with the intact spine model, the overall trend was that the ROM, intervertebral disc stress, and facet joint force decreased in the implanted level and increased in the adjacent level. When compared with the Ns-I, the trend in the Ns-F decreased and remained nearly half effect. Except for torsion, the PS stress of the Ns-F increased because of the sharing of NS stress after the NS fracture.Conclusions: The study concluded the biomechanical effects still afford nearly sufficient spine support and gentle adjacent segment stress after rod fracture in a worst-case scenario of the thinnest PS of the SHE rod system. [ABSTRACT FROM AUTHOR]

Background: The spinal hybrid elastic (SHE) rod dynamic stabilization system can provide sufficient spine support and less adjacent segment stress. This study aimed to investigate the biomechanical effects after the internal fracture of SHE rods using finite element analysis. Methods: A three-dimensional nonlinear finite element model was developed. The SHE rod comprises an inner nitinol stick (NS) and an outer polycarbonate urethane (PCU) shell (PS). The fracture was set at the caudal third portion of the NS, where the maximum stress occurred. The resultant intervertebral range of motion (ROM), intervertebral disc stress, facet joint contact force, screw stress, NS stress, and PCU stress were analyzed. Results: When compared with the intact spine model, the overall trend was that the ROM, intervertebral disc stress, and facet joint force decreased in the implanted level and increased in the adjacent level. When compared with the Ns-I, the trend in the Ns-F decreased and remained nearly half effect. Except for torsion, the PS stress of the Ns-F increased because of the sharing of NS stress after the NS fracture. Conclusions: The study concluded the biomechanical effects still afford nearly sufficient spine support and gentle adjacent segment stress after rod fracture in a worst-case scenario of the thinnest PS of the SHE rod system. [ABSTRACT FROM AUTHOR]

[Display omitted] • Structural optimizations of Moracin M resulted in several potent PDE4 inhibitors. • Lead L13 has an IC 50 of 36 ± 7 nM with remarkable selectivity. • L13 exhibits considerable drug-like profile. • L13 ·citrate displayed more significant anti-IPF effect than the marketed drug pirfenidone in vivo. • Docking studies on PDE4- L13 interactions mainly agree with the experimental results. Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and high mortality lung disease. Although the antifibrotic drugs pirfenidone and nintedanib could slow the rate of lung function decline, the usual course of the condition is inexorably to respiratory failure and death. Therefore, new approaches and novel therapeutic drugs for the treatment of IPF are urgently needed. And the selective PDE4 inhibitor has in vivo and in vitro anti-fibrotic effects in IPF models. But the clinical application of most PDE4 inhibitors are limited by their unexpected and severe side effects such as nausea, vomiting, and diarrhea. Herein, structure-based optimizations of the natural product Moracin M resulted in a novel a novel series of 2-arylbenzofurans as potent PDE4 inhibitors. The most potent inhibitor L13 has an IC 50 of 36 ± 7 nM with remarkable selectivity across the PDE families and administration of L13 ·citrate (10.0 mg/kg) exhibited comparable anti-pulmonary fibrosis effects to pirfenidone (300 mg/kg) in a bleomycin-induced IPF mice model, indicate that L13 is a potential lead for the treatment of IPF. [ABSTRACT FROM AUTHOR]

Quantitative differential phase-contrast (qDPC) imaging is a label-free phase retrieval method for weak phase objects using asymmetric illumination. However, qDPC imaging with fewer intensity measurements leads to anisotropic phase distribution in reconstructed images. In order to obtain isotropic phase transfer function, multiple measurements are required; thus, it is a time-consuming process. Here, we propose the feasibility of using deep learning (DL) method for isotropic qDPC microscopy from the least number of measurements. We utilize a commonly used convolutional neural network namely U-net architecture, trained to generate 12-axis isotropic reconstructed cell images (i.e. output) from 1-axis anisotropic cell images (i.e. input). To further extend the number of images for training, the U-net model is trained with a patch-wise approach. In this work, seven different types of living cell images were used for training, validation, and testing datasets. The results obtained from testing datasets show that our proposed DL-based method generates 1-axis qDPC images of similar accuracy to 12-axis measurements. The quantitative phase value in the region of interest is recovered from 66% up to 97%, compared to ground-truth values, providing solid evidence for improved phase uniformity, as well as retrieved missing spatial frequencies in 1-axis reconstructed images. In addition, results from our model are compared with paired and unpaired CycleGANs. Higher PSNR and SSIM values show the advantage of using the U-net model for isotropic qDPC microscopy. The proposed DL-based method may help in performing high-resolution quantitative studies for cell biology. [ABSTRACT FROM AUTHOR]

SelaginpulvilinsA–D (1–4), four new phenolswith an unprecedented 9,9-diphenyl-1-(phenylethynyl)-9H-fluorene skeleton, together with four known selaginellins(5–8) were isolated from Selaginella pulvinata. Their structures were elucidatedby spectroscopic analysis and chemical correlation. The structureof 1was confirmed by single-crystal X-ray diffraction.Compounds 1–8exhibited remarkableinhibitory activities (IC50values in the range of 0.11–5.13μM) against phosphodiesterase-4 (PDE4), a drug target for thetreatment of asthma and chronic obstructive pulmonary disease. [ABSTRACT FROM AUTHOR]

Abstract: The major role of disaster recovery management is to rapidly restore the chaotic condition to normal, which includes mitigation, preparedness, response, and recovery. To reduce secondary damage and loss, the recovery process must be facilitated. Information technologies (including network, web-based, computer, and related software tools) speed up the work process to rapidly deliver disaster information to the related department. In this paper, we share an experience that used a framework of emergency response, including a simple pre-operating process and a web-based information system, to effectively manage and control damaged medical equipment after a fire accident in a hospital operating room. This web-based information system was built in only 2weeks and was used to manage a large amount of medical equipment affected by the fire. Since then, it effectively prevented the interruption of clinical work at 22 clinical units by supporting the reconstruction activities. [Copyright &y& Elsevier]

Abstract: The tissue injury and the organization of collagen during cryosurgery are poorly characterized because of the lack of appropriate methodologies. In this study, we use multimodal multiphoton microscopy to assess the change of extracellular matrix after cryotreatment of skin. The cellular matrix transformations and the intercellular interactions during the wound healing process after cryolesion for mice were measured in vivo and in real-time through the dorsal skinfold chamber (DSC). Intrinsic second-harmonic generation (SHG) signals from fibrillar collagen and two-photon excited (TPE) autofluorescence from cell were collected to investigate the cryosurgical response in vivo. The TPE and SHG signals are significantly different between normal and cryotreated mice, and correlates with the wound healing process. The results suggest that this approach may be applied in real-time to noninvasively monitor the cryosurgery process and could potentially be applied to clinical evaluation. [Copyright &y& Elsevier]

In vivo and in vitro studies have confirmed that liquiritigenin (LQ), the primary active component of licorice, acts as an antitumor agent. However, how LQ diminishes or inhibits tumor growth is not fully understood. Here, we report the enzymatic inhibition of LQ and six other flavanone analogues towards AKR1Cs (AKR1C1, AKR1C2 and AKR1C3), which are involved in prostate cancer, breast cancer, and resistance of anticancer drugs. Crystallographic studies revealed AKR1C3 inhibition of LQ is related to its complementarity with the active site and the hydrogen bonds net in the catalytic site formed through C 7 –OH, aided by its nonplanar and compact structure due to the saturation of the C 2 C 3 double bond. Comparison of the LQ conformations in the structures of AKR1C1 and AKR1C3 revealed the induced-fit conformation changes, which explains the lack of isoform selectivity of LQ. Our findings will be helpful for better understanding the antitumor effects of LQ on hormonally dependent cancers and the rational design of selective AKR1Cs inhibitors. [Display omitted] • Liquiritigenin (LQ) was firstly found to inhibit AKR1Cs which are involved in hormonally dependent cancers. • Crystallographic study revealed LQ is complementary with AKR1C3 active site and forms H-bonds with the catalytic residues. • Comparison of LQ in the crystal structures of AKR1Cs showed a good example of induced-fit ligand conformation changes. [ABSTRACT FROM AUTHOR]

In recent decades, the decellularized extracellular matrix (ECM) has shown potential as a promising scaffold for tissue regeneration. In this study, an organic acid decellularized lymph node (dLN) was developed as a carrier for dendritic cells (DCs) to induce antitumor immunity. The dLNs were prepared by formic acid, acetic acid, or citric acid treatment. The results showed highly efficient removal of cell debris from the lymph node and great preservation of ECM architecture and biomolecules. In addition, bone marrow dendritic cells (BMDCs) grown preferably inside the dLN displayed the maturation markers CD80, CD86, and major histocompatibility complex (MHC)-II, and they produced high levels of interleukin (IL)-1β, IL-6, and IL-12 cytokines when stimulated with ovalbumin (OVA) and CpG oligodeoxynucleotides (CPG-ODN). In an animal model, the BMDC-dLN completely rejected the E.G7-OVA tumor. Furthermore, the splenocytes from BMDC-dLN-immunized mice produced more interferon gamma, IL-4, IL-6, and IL-2, and they had a higher proliferation rate than other groups when re-stimulated with OVA. Hence, BMDC-dLN could be a promising DC-based scaffold for in vivo delivery to induce potent antitumor immunity. [ABSTRACT FROM AUTHOR]

In the present study, we attempted to develop a lecithin-stabilized micellar drug delivery system (L sb MDDs) for loading docetaxel (DTX) to enhance its therapeutic efficacy and minimize systemic toxicity. A novel DTX-loaded L sb MDDs was optimally prepared by a thin-film hydration method and then hydrated with a lecithin nanosuspension while being subjected to ultrasonication. Physical characteristics of the optimized DTX-loaded L sb MDDs formulations were examined and found to have a mean size of <200 nm, an encapsulation efficiency of >90%, and drug loading of >6% with stability at room temperature and at 4 °C being longer than 2 and 7 days, respectively. The in vitro release of DTX from the DTX-loaded L sb MDDs was slower than that from the generic product of DTX (Tynen®). A cell viability assay demonstrated that the L sb MDDs showed better cytotoxicity than Tynen® against CT26 cancer cells. The in vivo antitumor efficacy of the DTX-loaded L sb MDDs was observed to be better than that of Tynen® in a CT26 tumor-bearing mice model. A high-dose regimen of the DTX-loaded L sb MDDs formulation showed greater inhibition of DU145 tumor growth than did Tynen®, but with less to similar systemic toxicity. An in vivo study also showed that a greater amount of drug was able to accumulate in the tumor site with the DTX-loaded L sb MDDs, and its maximal tolerable doses for single and repeated injections were 2–2.5-fold higher than those of Tynen®. In conclusion, the L sb MDDs could be a promising high drug-loaded nanocarrier for delivering hydrophobic chemotherapeutic agents that can enhance the efficacy of chemotherapy and reduce systemic toxicity. [ABSTRACT FROM AUTHOR]

Intracellular protein delivery may provide a safe and non-genome integrated strategy for targeting abnormal or specific cells for applications in cell reprogramming therapy. Thus, highly efficient intracellular functional protein delivery would be beneficial for protein drug discovery. In this study, we generated a cationic polyethyleneimine (PEI)-modified gelatin nanoparticle and evaluated its intracellular protein delivery ability in vitro and in vivo. The experimental results showed that the PEI-modified gelatin nanoparticle had a zeta potential of approximately +60 mV and the particle size was approximately 135 nm. The particle was stable at different biological pH values and temperatures and high protein loading efficiency was observed. The fluorescent image results revealed that large numbers of particles were taken up into the mammalian cells and escaped from the endosomes into the cytoplasm. In a mouse C26 cell-xenograft cancer model, particles accumulated in cancer cells. In conclusion, the PEI-modified gelatin particle may provide a biodegradable and highly efficient protein delivery system for use in regenerative medicine and cancer therapy. [ABSTRACT FROM AUTHOR]

Cavitation plays a substantial role in the clinical effects of extracorporeal shock wave therapy (ESWT). It is also generally accepted as a major mechanism in sonophoresis. To identify the enhancing effect of extracorporeal shock wave-mediated transdermal drug delivery, 24 Wistar rats were randomly assigned to four groups: (i) topical application of a eutectic mixture of local anesthetics (EMLA); (ii) 1-MHz ultrasound; (iii) ESWT pre-treatment combined with EMLA application; (iv) ESWT concurrent with EMLA application on rat tails. The degree of anesthesia was assessed using the amplitude and latency of sensory nerve action potentials within 5 min after a 60-min EMLA application. The results indicated that ESWT pre-treatment and concurrent ESWT accelerated the anesthetic effects of the EMLA cream on the tail nerve (p < 0.05). This finding might indicate that shock wave-mediated transdermal drug delivery is possible during the ESWT period. [ABSTRACT FROM AUTHOR]

The pathophysiology of cardio-renal syndrome (CRS) is complex. Hydronephrosis caused by urolithiasis may cause cytokine release and lead to cardiac dysfunction. The aim of this study was to evaluate cardiac function changes observed in patients who received double J placement using feasible biomarkers and echocardiography. This was a prospective, single-center study. Eighty-seven patients who presented with acute unilateral hydronephrosis and received ureteroscope stone manipulation were enrolled. Echocardiography and cytokines were measured on the day of the operation and 24 hours after the procedure. Changes before and after surgery were assessed by the paired t-test and Wilcoxon test. Correlation analyses between echocardiographic diastolic indices and cytokine levels were performed using Pearson’s correlation coefficients. Patients with hydronephrosis showed a higher left atrium volume index (LAVI), decreased E', and increased E/ E' ratio, which indicated diastolic dysfunction. Patients with hydronephrosis also exhibited decreased global strain rates during isovolumetric relaxation (SRIVR) and E/ SRIVR, which confirmed the diastolic dysfunction. Significant reductions in LAVI, increases in SRIVR and decreases in E/ SRIVR were observed after the operation. Biomarkers, such as TGF-β and serum NT-proBNP, were significantly decreased after surgery. In addition, a significant correlation was observed between the post-surgical decrease in TGF-β1 and increase in SRIVR. Unilateral hydronephrosis causes cardiac diastolic dysfunction, and relieving hydronephrosis could improve diastolic function. Improvements in cardiac dysfunction can be evaluated by echocardiography and measuring cytokine levels. The results of this study will inform efforts to improve the early diagnosis of CRS and prevent further deterioration of cardiac function when treating patients with hydronephrosis. [ABSTRACT FROM AUTHOR]

Inflammatory Bowel Diseases (IBDs) are chronic disorders with iterative intestinal mucosal inflammation which remain unmet medical needs. PDE4 inhibitors were reported to be novel anti-IBD agents, but their clinical use was hampered by side effects such as emesis and nausea. Herein, structure-based discovery of natural mangostanin (1) targeting the M-pocket resulted in the novel and potent PDE4 inhibitor 22d (IC 50 = 3.5 nM) and favorable physico-chemical properties. X-Ray study revealed that 22d interacted tightly with the M-pocket and maintained the key interactions between PDE4 and roflumilast. Worthy to note that compounds 22d and our previously reported 4e and 18a , originating from mangostanin, all caused no emesis on beagle dogs at the oral dose of 10 mg/kg, confirming the safety superiority of scaffold in mangostanin derivatives over that in positive roflumilast. Finally, administration of 22d (5.0 mg/kg, twice-daily) exhibited comparable anti-IBD effects to the positive control dipyridamole (25.0 mg/kg, twice-daily) in the dextran sulfate sodium (DSS)-induced IBD mice model, indicating its potential as a novel anti-IBD agent. [Display omitted] • Lead 22d had maintained the safety superiority of the mangostanin scaffold (emetic dose >10 mg/kg) and simulated the key interactions between PDE4 and highly potent roflumilast (inhibitory IC 50 of 3.5 nM). • Lead 22d was a potential novel agent for treatment of Inflammatory Bowel Diseases. • Their co-crystal structures revealed that interacting with the M pocket was an effective strategy to improve the potencies of PDE4 inhibitors. [ABSTRACT FROM AUTHOR]

[Display omitted] Phosphodiesterase-4 (PDE4) is an important drug target for inflammatory diseases. Previously, we identified a series of novel PDE4 inhibitors derived from the natural Toddacoumalone, among which the hit compound 2 with a naphthyridine scaffold showed moderate potency with the IC 50 value of 400 nM. Based on the co-crystal structure of PDE4D- 2 , further structural optimizations and structure–activity relationship studies led to a highly potent PDE4 inhibitor 23a with the IC 50 value of 0.25 nM and excellent selectivity profiles over other PDEs (>4000-fold). The co-crystal structure of PDE4D- 23a elucidated that 23a has strong interactions with the M and Q pocket of PDE4D. Importantly, compound 23a significantly inhibits the release of inflammatory cytokines TNF- α and IL-6 in lipopolysaccharide-stimulated RAW264.7 cells. Thus, compound 23a with a naphthyridine scaffold is a promising PDE4 inhibitor for the treatment of inflammatory diseases. [ABSTRACT FROM AUTHOR]

Background: Reconstruction of a segmental fracture with massive bone loss is still a challenge for orthopaedic surgeons. The aim of our study was to develop a suitable biodegradable thermosensitive hydrogel system as a carrier for bone morphogenetic protein (BMP)-2 delivery in the treatment of critical-sized femoral defects.Methods: A block copolymer composed of monomethoxypoly(ethylene glycol) (mPEG), poly(lactic-co-glycolic acid) (PLGA) and 2, 2'-Bis (2-oxazolin) (Box) was synthesized by ring opening polymerization. The synthesized block copolymer was characterized by (1)H-NMR spectroscopy and gel permeation chromatography (GPC). Different biophysical and biochemical properties of the synthesized copolymer, including temperature-induced structure changes, degradation rate, pH changes during hydrolytic degradation, cell toxicity, and the release profile of BMP-2, were also evaluated and/or were compared with those of a well-characterized mPEG-PLGA copolymer. In animal testing, rabbits (n = 36) that received critically sized (10 mm) femoral defects were divided into 6 groups. These experimental groups included an untreated group, autograft, and groups treated with the synthesized copolymer carrying different concentrations of BMP-2 (0, 5, 10, and 20 μg/ml). Bone repair was evaluated using X-ray radiography, histological staining, micro-computed tomography (μCT), biomarker examination and biomechanical testing in a 12-week treatment period.Results: A new thermosensitive mPEG-PLGA/Box/mPEG-PLGA block copolymer, or named as BOX copolymer, was successfully prepared. Compared to the reported mPEG-PLGA in vitro, the prepared BOX copolymer at the same weight percent concentrations exhibited wider temperature ranges of gelation, slower degradation rates, higher the pH values, as well as less cytotoxicity. Furthermore, the BMP-2 release from BOX hydrogel exhibited a near-linear release profile in vitro. In animal experiments, treatment of critical-sized bony defects with 25 wt% BOX hydrogel carrying BMP-2 effectively promoted fracture healing during the 12-week trial period and higher concentrations of BMP-2 treatment correlated with better bone quality. Most importantly, clinical outcome and bone healing in the BOX-hydrogel group with 20 μg/ml BMP-2 were nearly equivalent to those in the autograft group in a 12-week treatment course.Conclusion: These data support that the use of BOX hydrogel (25 wt%) as a drug delivery system is a promising method in the treatment of large bone defects. [ABSTRACT FROM AUTHOR]

Abstract: In this study, plasma deposition methods were used to immobilize Au electrode of a quartz crystal microbalance (QCM) to create different microenvironments for mass measurement of various modified Au nanoparticles (AuNPs). AuNPs were modified by 11-mercaptoundecanoic acid (MUA) and 1-decanethiol (DCT) for potential applications to drug release, protective coatings, and immunosensors. We aimed to develop a highly sensitive and reliable method to quantify the mass of various modified AuNPs. The surface of AuNPs and Au electrode was coated with polymer films, as determined by Fourier transform infrared spectroscopy and atomic force microscopy. Measurements obtained for various AuNPs and the plasma-treated surface of the Au electrode were compared with those obtained for an untreated Au electrode. According to the resonant frequency shift of QCM, a linear relationship was observed that significantly differed for AuNPs, MUA-AuNPs, and DCT-AuNPs (R 2 range, 0.94–0.965, 0.934–0.972, and 0.874–0.9514, respectively). Compared to inductively coupled plasma and micro-computerized tomography, the QCM method with plasma treatment has advantages of real-time monitoring, greater sensitivity, and lower cost. Our results demonstrate that surface modifications measured by a QCM system for various modified AuNPs were reliable. [Copyright &y& Elsevier]

The article presents a chemical formula related to the article "Selaginpulvilins A-D, New Phosphodiesterase-4 Inhibitors with an Unprecedented Skeleton from Selaginella pulvinata" by X. Liu and others, published in the periodical "Organic Letters" in 2014.

Abstract: Spinal cord injury (SCI) can trigger inhibitory signal cascades that promote the expression of chondroitin sulfate proteoglycans (CSPGs), which are the main structures in scar tissue. The digestion of CSPGs by chondroitinase ABC (ChABC) can promote axonal re-growth after SCI. However, ChABC cannot effectively digest CSPGs because it is unstable; therefore, stable ChABC must be released in a controlled manner in the repair of SCIs. Two methods of maintaining ChABC stability and bioactivity were examined. They were the immobilization of ChABC on nerve conduits (NCs) and the encapsulation of ChABC in poly(d,l-lactic acid) (PDLLA) microspheres. Nerve conduits with variously sized pores were fabricated from chitosan and gelatin. The pore diameters of chitosan NCs were 100–160μm, and those of chitosan/gelatin NCs were 20–40μm. The ChABC in NCs was immobilized by ionic or covalent bonding. The experimental results reveal that immobilizing ChABC in NCs markedly improved its stability. The activity of ChABC that was immobilized in chitosan NCs by ionic bonding was 0.07U/mg; 48% of this activity was retained at 48h after immobilization. PDLLA microspheres, fabricated by the double emulsion method, were applied as carriers in the controlled release of ChABC. Stabilizers, including nanogold (10nm), polylysine (Mw: 500–2000) and polylysine (Mw: 20,000–30,000), were added to microspheres to maintain the activity of ChABC. Polylysine (Mw: 500–2000) stabilized ChABC most effectively. The ChABC activity was 0.0162U/ml after seven days of release. Experimental results indicate that ChABC activity can be preserved during release by immobilizing ChABC in chitosan NCs and encapsulating ChABC in PDLLA microspheres using an appropriate stabilizer. [Copyright &y& Elsevier]

Abstract: Poly(ε-caprolactone) (PCL) scaffolds were modified by grafting nerve growth factor (NGF) and Tirofiban (TF), a clinical anti-thrombosis drug, as a new biomaterial for producing nerve conduits to promote the regeneration of sciatic nerves. The successful grafting of NGF and TF onto PCL scaffolds was confirmed by FTIR and ESCA spectra. In-vitro growths of the PC12 cells in PCL-NGF and PCL-NGF/TF scaffolds, determined by MTS, were significantly higher (P < 0.05, n = 4) than those in the PCL scaffolds following three days of cultivation. Interestingly, this study evaluation of the PCL, PCL-NGF, and PCL-NGF/TF nerve conduits in a 12 mm long gap of the rat sciatic nerve defect model that the gastrocnemius muscle mass of the tested rats in the PCL-NGF/TF groups significantly exceeded those in the PCL-NGF and PCL group. In the rats that had been implanted with PCL-NGF/TF conduits, the generated nerves passed through those conduits, expressing beta-III tubulin (TB), growth association protein-43 (GAP-43) and myelin basic protein (MBP) along their longitudinal axis, and the proximal and distal nerve ends of the rats were successfully connected. Those that had been implanted with PCL and PCL-NGF conduits did not exhibit these effects, as revealed by an immunochemical study of the expressions of the proteins in the conduits. Moreover, counting within the dorsal horn of the spinal cord (C5) demonstrated that the numbers of CTB-HRP-labeled neurons in the rats that had been implanted with PCL-NGF/TF conduits were significantly higher than those in the other groups. In this study, in-vivo examinations of the use of newly designed PCL-NGF/TF conduits to promote the generation of nerves in a defective rat model significantly increased the gastrocnemius muscle mass, and led to the successful regeneration of nerves that bridged a 12 mm long defected gap of nerves in rats. However, more rats must be tested to confirm the efficacy the newly designed nerve conduits. [Copyright &y& Elsevier]

Abstract: Using excitation polarization-resolved second harmonic generation (SHG) microscopy, we measured SHG intensity as a function of the excitation polarization angle for type I and type II collagens. We determined the second order susceptibility (χ(2)) tensor ratios of type I and II collagens at each pixel, and displayed the results as images. We found that the χ(2) tensor ratios can be used to distinguish the two types of collagen. In particular, we obtained χ zzz/χ zxx = 1.40 ± 0.04 and χ xzx/χ zxx = 0.53 ± 0.10 for type I collagen from rat tail tendon, and χ zzz/χ zxx = 1.14 ± 0.09 and χ xzx/χ zxx = 0.29 ± 0.11 for type II collagen from rat trachea cartilage. We also applied this methodology on the label-free imaging of engineered cartilage tissue which produces type I and II collagen simultaneously. By displaying the χ(2) tensor ratios in the image format, the variation in the χ(2) tensor ratios can be used as a contrast mechanism for distinguishing type I and II collagens. [Copyright &y& Elsevier]

Abstract: Since MSCs contain an abundant of CD44 surface markers, it is of interesting to investigate whether CD44 on rat MSC (rMSCs) influenced cell growth, fibronectin expression and cardiomyogenic differentiation on new SF/HA cardiac patches. For this investigation, we examined the influences of rMSCs with or without a CD44-blockage treatment on the aforementioned issues after they were cultivated, and further induced by 5-aza on SF and SF/HA patches. The results showed that the relative growth rates of rMSCs cultured on cultural wells, SF/HA patches without or with a CD44-blockage treatment were 100%, 208.9±7.1 (%) or 48.4±6.0 (%) (n =3, for all), respectively, after five days of cultivations. Moreover, rMSCs cultivated on SF/HA patches highly promoted fibronectin expressions (e.g., 1.8×105/cell, in fluorescent intensity) while cells with a CD44-blockage treatment markedly diminished the expressions (e.g., 1.1×104/cell, in fluorescent intensity) on same patches. For investigating possible influences of CD44 surface markers of rMSCs on their cardiomyogenic differentiation, the expressions of specific cardiac genes of cells were examined by using real-time PCR analysis. The results indicated that 5-aza inducing rMSCs significantly promoted the expressions of Gata4, Nkx2.5, Tnnt2 and Actc1 genes (all, P <0.01 or better, n =3) on SF/HA patches compared with those expressions on SF patches and for cells with a CD44-blockage treatment on SF/HA patches. Furthermore, the intensity of the expressions of cardiotin and connexin 43 of 5-aza inducing rMSCs were markedly higher than those of cells with a CD44-blockage treatment after they were cultured on SF/HA patches. Through this study, we reported that CD44 surface markers of rMSCs highly influenced the proliferations, fibronectin expressions and cardiomyogenic differentiation of rMSCs cultivated on cardiac SF/HA patches. [Copyright &y& Elsevier]

Abstract: In order to potentiate the low immunogenicity of the inactivated Newcastle disease virus immunized into chickens by mucosal route, liposomes as a drug delivery system and LPS (lipopolysaccharide) as an immuno-stimulator were evaluated. Here, we report a new nasal delivery system of inactivated Newcastle disease virus (NDV) vaccine. The intranasal vaccine was based on different lipids to form MLV (multi-lamellar vehicles) liposomes. The liposomes had combined carrier and adjuvant activities, which induced strong systemic (serum) and local (lung and nasal) humoral responses in SPF (specific-pathogen-free) chickens, and provided protective immunity. PC-Lip (phosphatidylcholine-liposome) elicited significant mucosal secretary immunoglobulin A (s-IgA) levels (p <0.05) in tracheal lavage fluid and serum IgG levels (p <0.05). In response to virulent viral challenge, birds treated with PBS (phosphate buffered saline) as control group died, whereas 80% of chickens which received PC-Lip, PC-Lip-LPS, PS-Lip (phosphatidylserine-liposome), and PS-Lip-LPS survived. HAI titers were 1:2560 in the PS-Lip-LPS group and 1:1280 in the PC-Lip, PC-Lip-LPS, and PS-Lip groups after two vaccinations. The results suggest that PC-Lip or PS-Lip might thus be suitable as a potential adjuvant for mucosal vaccination against NDV in chickens. [Copyright &y& Elsevier]

Abstract: The aim of this study was to characterize a nasally delivered bioadhesive liposome using an inactivated H5N3 virus as a model antigen. Bioadhesive liposomes were developed using tremella (T) or xanthan gum (XG) as the bioadhesive polysaccharide. Using chickens as the target animal, we evaluated whether delivery of a bioadhesive liposomal influenza vaccine via a mucosal site of infection could improve vaccine effectiveness. 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) cytotoxicity assays demonstrated that T, XG and liposomes were non toxic to chicken spleen macrophages. Enzyme-linked immunosorbent assay (ELISA) was used to determine the adjuvant effect of the bioadhesive liposomal-vaccines. Chickens immunized with a low dose (200μL) of bioadhesive liposomal influenza vaccine had significantly higher mucosal and serum antibody levels (P <0.05). In addition, liposomes mixed with a low-viscosity bioadhesive gel used for nasal delivery resulted in superior antibody responses compared with liposomes mixed with a high-viscosity gel (P <0.05). This suggest that a low-viscosity gel mixed with liposomes is more suitable for nasal delivery, and that chickens elicit higher mucosal secretory immunoglobulin A (s-IgA) and serum IgG after two vaccinations. [Copyright &y& Elsevier]

Abstract: Polysaccharides and proteins profoundly impact the development and growth of tissues in the natural extra-cellular matrix (ECM). To mimic a natural ECM, polysaccharides were incorporated to/or co-sprayed with silk fibroin (SF) to produce SF/chitosan (CS) or SF/CS–hyaluronic acid (SF/CS–HA) microparticles that were further processed by mechanical pressing and genipin cross-linking to produce hybrid cardiac patches. The ATR–FTIR spectra confirm the co-existence of CS or CS–HA and SF in microparticles and patches. For evaluating the cellular responses of rMSCs to the SF/CS and SF/CS–HA cardiac patches, the growth of rMSCs and cardiomyogenic differentiation of 5-aza inducing rMSCs cultured on patches was examined. First, the isolated rMSCs were identified with various positive and negative surface markers such as CD 44 and CD 31 by a flow cytometric technique, respectively. For examining the growth of rMSCs on the patches, MTT viability assay was performed, and the results demonstrated that the growth of rMSCs on SF and SF-hybrid patches significantly exceeded (P <0.001) that on culture wells after seven days of cultivation. Additionally, the relative growth rates of rMSCs on SF/CS and SF/CS–HA hybrid patches were significantly better (P <0.01) than that on SF patches that were also observed by using vimentin stain to the cells. For instance, the relative cell growth rates (%) in cell culture wells, SF, SF/CS and SF/CS–HA patches were 100%, 282.9±6.5%, 337.0±8.0% and 332.6±6.6% (n =6, for all), respectively. For investigating the effects of the hybrid patches on cardiomyogenic differentiation of 5-aza inducing rMSCs, the expressions of specific cardiac genes of cells such as Gata4 and Nkx2.5 were examined by real-time quantitative polymerase chain reaction (real-time PCR) analysis. The results of cardiomyogenic differentiation of induced rMSCs on SF/CS and SF/CS–HA hybrid patches significantly improved the expressions of cardiac genes of Gata4, Nkx2.5, Tnnt2 and Actc1 genes (all, P <0.01 or better, n =3) than those on SF patches and culture wells. Interestingly, the results of cardiac gene expressions of the cells on the SF/CS–HA hybrid patches were the most pronounced in promoting cardiomyogenic differentiations in this investigation. Furthermore, immunofluorescence staining of cardiac proteins such as cardiotin and connexin 43 for induced rMSCs cultured on SF/CS and SF/CS–HA hybrid patches were much pronounced compared with SF patches, indicating the improvements of cardiomyogenic differentiation on the hybrid patches. The results of this study demonstrate that the SF/CS and SF/CS–HA hybrid patches may be promising biomaterials for regenerating infarcted cardiac tissues. [Copyright &y& Elsevier]

Autologous chondrocyte implantation (ACI) has been recently used to treat cartilage defects. Partly because of the success of mosaicplasty, a procedure that involves the implantation of native osteochondral plugs, it is of potential significance to consider the application of ACI in the form of biphasic osteochondral composites. To test the clinical applicability of such composite construct, we repaired osteochondral defect with ACI at low cell-seeding density on a biphasic scaffold, and combined graft harvest and implantation in a single surgery. We fabricated a biphasic cylindrical porous plug of DL-poly-lactide-co-glycolide, with its lower body impregnated with β-tricalcium phosphate as the osseous phase. Osteochondral defects were surgically created at the weight-bearing surface of femoral condyles of Lee-Sung mini-pigs. Autologous chondrocytes isolated from the cartilage were seeded into the upper, chondral phase of the plug, which was inserted by press-fitting to fill the defect. Defects treated with cell-free plugs served as control. Outcome of repair was examined 6 months after surgery. In the osseous phase, the biomaterial retained in the center and cancellous bone formed in the periphery, integrating well with native subchondral bone with extensive remodeling, as depicted on X-ray roentgenography by higher radiolucency. In the chondral phase, collagen type II immunohistochemistry and Safranin O histological staining showed hyaline cartilage regeneration in the experimental group, whereas only fibrous tissue formed in the control group. On the International Cartilage Repair Society Scale, the experimental group had higher mean scores in surface, matrix, cell distribution, and cell viability than control, but was comparable with the control group in subchondral bone and mineralization. Tensile stress-relaxation behavior determined by uni-axial indentation test revealed similar creep property between the surface of the experimental specimen and native cartilage, but not the control specimen. Implanted autologous chondrocytes could survive and could yield hyaline-like cartilage in vivo in the biphasic biomaterial construct. Pre-seeding of osteogenic cells did not appear to be necessary to regenerate subchondral bone. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1277-1290, 2007 [ABSTRACT FROM AUTHOR]

Abstract: To better direct the repair of damaged axons following spinal cord injury (SCI), we designed a nerve conduit (NC) modeled after the intact spinal cord, which would enable the axons to cross the lesioned area to rejoin on the other side. The NC consisted of a porous chitosan scaffold and was incorporated with laminin (LN) on the inner surface through oxygen plasma treatment. According to the BBB, CBS, and treadmill analyses, we found that following the implantation of the laminin-coated NC (LN-NC) the rats showed a tendency towards behavior improvement and functional recovery. Histology and immunocytochemical analyses indicated that the NC groups were capable of leading the damaged axons through the lesioned area without triggering inflammation or apoptosis. Together with the significantly enhanced expression of local GAP-43 in the LN-NC groups, as evidenced by western blot analysis, axon re-growth mediated by LN-NC was found to compare better than that by NC group. These results suggest a new possible approach to repairing SCI and, in general, a model which will be useful for other multidisciplinary procedures for complex neurological situations. [Copyright &y& Elsevier]

Abstract: Articular cartilage is known to have poor healing capacity after injury. Autologous chondral grafting remains the mainstay to treat well-defined, full-thickness, symptomatic cartilage defects. We demonstrated the utilization of gelatin microbeads to deliver autologous chondrocytes for in vivo cartilage generation. Chondrocytes were harvested from the left forelimbs of 12 Lee-Sung pigs. The cells were expanded in monolayer culture and then seeded onto gelatin microbeads or left in monolayer. Shortly before implantation, the cell-laden beads were mixed with collagen type I gel, while the cells in monolayer culture were collected and re-suspended in culture medium. Full-thickness cartilage defects were surgically created in the weight-bearing surface of the femoral condyles of both knees, covered by periosteal patches taken from proximal tibia, and sealed with a porcine fibrin glue. In total, 48 condyles were equally allotted to experimental, control, and null groups that were filled beneath the patch with chondrocyte-laden beads in gel, chondrocytes in plain medium solution, or nothing, respectively. The repair was examined 6 months post-surgery on the basis of macroscopic appearance, histological scores based on the International Cartilage Repair Society Scale, and the proportion of characteristic chondrocytes. Tensile stress-relaxation behavior was determined from uniaxial indentation tests. The experimental group scored higher than the control group in the categories of matrix nature, cell distribution pattern, and absence of mineralization, with similar surface smoothness. Both the experimental and control groups were superior to the null group in the above-mentioned categories. Viable cell populations were equal in all groups, but the proportion of characteristic chondrocytes was highest in the experimental group. Matrix stiffness was ranked as null>native cartilage>control>experimental group. Transplanted autologous chondrocytes survive and could yield hyaline-like cartilage. The application of beads and gel for transplantation helped to retain the transferred cells in situ and maintain a better chondrocyte phenotype. [Copyright &y& Elsevier]

Intravitreal injections are clinically established procedures in the treatment of posterior eye diseases, such as wet age-related macular degeneration (wet AMD) which requires monthly intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) protein drugs that can lead to complications due to frequent dosing. In this study, we designed a composite drug delivery system (DDS) consisting of drug-loaded poly (lactide–co–glycolide) (PLGA) nanoparticles and a chemically crosslinked hyaluronan hydrogel to reduce the dosing frequency. The morphology, size, composition, and drug loading efficiency of the prepared nanoparticles were characterized. The properties of the modified hyaluronan polymers used were also examined. The degree of swelling/degradation and controlled release ability of the hyaluronan hydrogel and the composite DDS were identified using bovine serum albumin (BSA) as a model drug. The results show that this system can retain 75% of its wet weight without losing its integrity and release the model drug at the rate of 0.4 μg/day for more than two months under physiological conditions. In addition, the nanoparticulate formulation of the system can further improve bioavailability of the drugs by penetrating deep into the retinal layers. In conclusion, the proposed composite DDS is easily prepared with biocompatible materials and is promising for providing the sustained release of the protein drugs as a better treatment for ocular neovascular diseases like wet AMD. [ABSTRACT FROM AUTHOR]

Significance: Differential phase contrast (DPC) is a well-known imaging technique for phase imaging. However, simultaneously acquiring multidepth DPC images is a non-trivial task. We propose simultaneous multiplane DPC imaging using volume holographic microscopy (VHM). Aim: To design and implement a new configuration of DPC-VHM for multiplane imaging. Approach: The angularly multiplexed volume holographic gratings (AMVHGs) and the wavelength-coded volume holographic gratings (WC-VHGs) are used for this purpose. To obtain asymmetric illumination for DPC images, a dynamic illumination system is designed by modifying the regular Köhler illumination using a thin film transistor panel (TFT-panel). Results: Multidepth DPC images of standard resolution chart and biosamples were used to compare imaging performance with the corresponding bright-field images. An average contrast enhancement of around three times is observed for target resolution chart by DPC-VHM. Imaging performance of our system is studied by modulation transfer function analysis, which suggests that DPC-VHM not only suppresses the DC component but also enhances high-frequency information. Conclusions: Proposed DPC-VHM can acquire multidepth-resolved DPC images without axial scanning. The illumination part of the system is adjustable so that the system can be adapted to bright-field mode, phase contrast mode, and DPC mode by controlling the pattern on the TFT-panel. [ABSTRACT FROM AUTHOR]