Tacrolimus and paclitaxel co-loaded O/O ointment without surfactant: Synergistic combinations for the treatment of psoriasis.

Psoriasis is an autoimmune disorder disease with abnormally activated T lymphocytes and thickening of the epidermis. The mechanism of the action of tacrolimus and paclitaxel are matched with the two only known pathogenesis of psoriasis. However, there has been no report on tacrolimus combined with paclitaxel in the treatment of psoriasis until now. The O/O ointment was prepared for the topical application to overcome poor solubility, poor skin penetration, and erratic absorption of the two drugs. A high-speed shearing method was adopted to prepare the ointment, in which propylene carbonate was used to solve tacrolimus and paclitaxel completely. The ointment showed excellent stability, slow release of the drugs, better retention in psoriatic skin, and good skin tolerance. The therapeutic efficacy of ointment was evaluated with imiquimod induced psoriatic model, and the level of expression of psoriatic biochemical markers was evaluated using the PASI score and immunohistochemistry. The cumulative PASI score was 10.8 for the imiquimod induced group, 7.8 for the tacrolimus ointment group, 8.3 for the paclitaxel ointment and 5.3 for the tacrolimus-paclitaxel (1:1) ointment group, respectively. Ointment group with tacrolimus and paclitaxel indicated a significant improvement in the phenotypic features of the psoriatic skin treated. Compared with the imiquimod group, tacrolimus-paclitaxel (1:1) ointment group was significantly reduced the level of IL-17. The results confirm that tacrolimus and paclitaxel co-loaded ointment can be an effective strategy for the treatment of psoriasis.

Solid-in-oil nanodispersion as a novel topical transdermal delivery to enhance stability and skin permeation and retention of hydrophilic drugs l-ascorbic acid.

l-ascorbic acid （Vitamin C, VC） is the most abundant antioxidant in human skin. But its poor penetration into the skin and unstability limit the application. The aim of the study was to promote the topical skin permeation and retention of VC, increase the stability as well as effectiveness by a novel solid in oil nanodispersion. In the nanodispersions system, nano-sized particles of hydrophilic molecules are dispersed in an oil vehicle with the assistance of hydrophobic surfactants. The optimized formula composed of O170 and S1570 (12.5:1, w/w) showed high EE% of 98% and good stability. FTIR analysis confirmed that there may be hydrogen bond between VC and surfactants. The results of DSC, and XRD revealed that the drug was successfully encapsulated in the surfactants, which maintained the stability of drug. By analyzing and fitting the release data in vitro, the drug release mechanism of SONDs was predicted as a multi-dynamic model. Skin permeation of VC was improved 3.43-fold for SONDs compared with VC aqueous solution, highlighting that the lipophilicity and nano size of the carrier more easily penetrated into the skin. Finally, the photoaging study revealed that topical application of VC-SONDs provided the highest skin protection compared UV and VC aqueous solution treated group which was evident by the normal thick epidermal morphology, no obvious melanocytes and the densely arranged dermal elastic fibers. These results demonstrated that the solid-in-oil nanodispersions may be a potential transdermal delivery system for hydrophilic bioactive ingredients.

Pharmacological Mechanisms Underlying the Hepatoprotective Effects of Ecliptae herba on Hepatocellular Carcinoma.

BACKGROUND: The number of hepatocellular carcinoma (HCC) cases worldwide has increased significantly. As a traditional Chinese medicine (TCM) with a long history, Ecliptae herba (EH) has been widely used in HCC patients in China, but its hepatoprotective mechanism is still unclear. METHODS: In this study, we applied a network pharmacology-based strategy and experimental verification to systematically unravel the underlying mechanisms of EH against HCC. First, six active ingredients of EH were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) by the ADME method. Subsequently, 52 potential targets of 6 active ingredients acting on HCC were screened from various databases, including TCMSP, DGIdb, SwissTargetPrediction, CTD, and GeneCards. Then, by constructing protein-protein interaction (PPI) network from STRING, we displayed the intricate connections among these 52 targets through Cytoscape software. We also applied enrichment analysis, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, to provide an outline and set of concepts for describing gene functions and the advanced functions of biological systems of these 52 targets from genomic and molecular level information. Finally, molecular docking and biological experiments were used to reconfirm these results. RESULTS: We hypothesized that EH might exert anti-HCC activity by acting on hub genes, including RELA, MMP9, PTGS2, ESR1, EGFR, AR, AKT1, HIF1A, AHR, CYP3A4, ABCG2, and MMP2. Moreover, based on GO and KEGG analysis, we speculated that EH may exert hepatoprotective effects on HCC through the following mechanisms: regulation of the PI3K-AKT signaling pathway to promote apoptosis and inhibit the abnormal proliferation of HCC, downregulation of HIF-1A expression by activating the HIF-1 signaling pathway, prevention of HCC by regulating lipid metabolism, and inhibition of nonalcoholic fatty liver disease (NAFLD) by the cytochrome P450 subfamily. Subsequent biological experiments verified that EH inhibits the PI3K-AKT signaling pathway through its active ingredients, quercetin, and wedelolactone, thereby inhibiting the proliferation of HCC cells and promoting the apoptosis of HCC cells. CONCLUSIONS: The network pharmacological strategy provides an efficient method to systematically explore the pharmacological mechanism of EH in HCC. Our study demonstrated that the anti-HCC proliferation activity of EH is mainly exerted by two active ingredients (quercetin and wedelolactone), which inhibit the proliferation of HCC cells (HepG2 and Huh-7) by inhibiting PI3K-AKT signaling.

Repetitive Transcranial Magnetic Stimulation on the Affected Hemisphere Enhances Hand Functional Recovery in Subacute Adult Stroke Patients: A Randomized Trial.

Objectives: Either motor training or repetitive transcranial magnetic stimulation (rTMS) could modulate the neural plasticity after stroke. Therefore, synchronizing the two interventions may optimize the efficiency of recovery. In the present study, we aim to investigate the effect of rTMS along with hand grip training on the neurobehavioral and hand functional recovery in one cohort of subacute stroke patients. Methods: Thirty-nine stroke patients were enrolled in a single-center, single-blinded, randomized clinical trial. We tested different intervention effects of rTMS and hand grip training (group A), rTMS alone (group B), and hand grip training alone (group C). For the rTMS-treated groups, patients received 10 consecutive sessions of 5-Hz stimulation over the affected hemisphere with 750 pulses. Jebsen-Taylor Hand Function Test (JTHFT), Fugl-Meyer assessment of upper extremity (FMA-UE), grip strength, modified Barthel index (mBI), and ipsilesional motor evoked potential (iMEP) latency were assessed and compared across the groups. Results: We found that only rTMS along with hand grip training group all improved in JTHFT, FMA-UE, grip strength, and mBI (p ≤ 0.01) compared with the baseline among the three groups. Furthermore, this study demonstrated that rTMS plus hand grip training had much better results in improvement of neurobehavioral outcomes compared to the rTMS alone- and hand grip training alone-treated patients (p < 0.05). However, no significant differences were detected in neurophysiologic outcome between intra-groups and inter-groups (p > 0.05). Conclusion: These proof-of-concept results suggested that rTMS alone with hand grip training was a unique approach to promote hand functional recovery in stroke patients. It provided important information to design a large-scale multi-center clinical trial to further demonstrate the efficiency of the combination of central and peripheral stimulation. Clinical Trial Registration: http://www.chictr.org.cn (#ChiCTR1900023443).

Combined effect of repetitive transcranial magnetic stimulation and physical exercise on cortical plasticity.

Physical exercise can minimize dysfunction and optimize functional motor recovery after stroke by modulating cortical plasticity. However, the limitation of physical exercise is that large amounts of time and effort are necessary to significantly improve motor function, and even then, substantial exercise may not be sufficient to normalize the observed improvements. Thus, interventions that could be used to strengthen physical exercise-induced neuroplasticity may be valuable in treating hemiplegia after stroke. Repetitive transcranial magnetic stimulation seems to be a viable strategy for enhancing such plasticity. As a non-invasive cortical stimulation technique, repetitive transcranial magnetic stimulation is able to induce long-term plastic changes in the motor system. Recently, repetitive transcranial magnetic stimulation was found to optimize the plastic changes caused by motor training, thereby enhancing the long-term effects of physical exercise in stroke patients. Therefore, it is believed that the combination of repetitive transcranial magnetic stimulation and physical exercise may represent a superior method for restoring motor function after stroke.

The Effects of Combined Low Frequency Repetitive Transcranial Magnetic Stimulation and Motor Imagery on Upper Extremity Motor Recovery Following Stroke.

Objective: To investigate the effects of low frequency transcranial magnetic stimulation (LF-rTMS) combined with motor imagery (MI) on upper limb motor function during stroke rehabilitation. Background: Hemiplegic upper extremity activity obstacle is a common movement disorder after stroke. Compared with a single intervention, sequential protocol or combination of several techniques has been proven to be better for alleviating motor function disorder. Non-invasive neuromodulation techniques such as repetitive transcranial magnetic stimulation (rTMS) and motor imagery (MI) have been verified to augment the efficacy of rehabilitation. Methods:Participants were randomly assigned to 2 intervention cohorts: (1) experimental group (rTMS+MI group) was applied at 1 Hz rTMS over the primary motor cortex of the contralesional hemisphere combined with audio-based MI; (2) control group (rTMS group) received the same therapeutic parameters of rTMS combined with audiotape-led relaxation. LF-rTMS protocol was conducted in 10 sessions over 2 weeks for 30 min. Functional measurements include Wolf Motor Function Test (WMFT), the Fugl-Meyer Assessment Upper Extremity (UE-FMA) subscore, the Box and Block Test (BBT), and the Modified Barthel index (MBI) were conducted at baseline, the second week (week 2) and the fourth week (week 4). Results: All assessments of upper limb function improved in both groups at weeks 2 and 4. In particular, significant differences were observed between two groups at end-intervention and after intervention (p < 0.05). In these findings, we saw greater changes of WMFT (p < 0.01), UE-FMA (p < 0.01), BBT (p < 0.01), and MBI (p < 0.001) scores in the experimental group. Conclusions: LF-rTMS combined with MI had a positive effect on motor function of upper limb and can be used for the rehabilitation of upper extremity motor recovery in stroke patients.

Feasibility study on nondestructively sensing meat's freshness using light scattering imaging technique.

Rich nutrient matrix meat is the first-choice source of animal protein for many people all over the world, but it is also highly susceptible to spoilage due to chemical and microbiological activities. In this work, we attempted the feasibility study of rapidly and nondestructively sensing meat's freshness using a light scattering technique. First, we developed the light scattering system for image acquisition. Next, texture analysis was used for extracting characteristic variables from the region of interest (ROI) of a scattering image. Finally, a novel classification algorithm adaptive boosting orthogonal linear discriminant analysis (AdaBoost-OLDA) was proposed for modeling, and compared with two classical classification algorithms linear discriminant analysis (LDA) and support vector machine (SVM). Experimental results showed that classification results by AdaBoost-OLDA algorithm are superior to LDA and SVM algorithms, and eventually achieved 100% classification rate in the calibration and prediction sets. This work demonstrates that the developed light scattering technique has the potential in noninvasively sensing meat's freshness.

Real-time monitoring of process parameters in rice wine fermentation by a portable spectral analytical system combined with multivariate analysis.

A portable and low-cost spectral analytical system was developed and used to monitor real-time process parameters, i.e. total sugar content (TSC), alcohol content (AC) and pH during rice wine fermentation. Various partial least square (PLS) algorithms were implemented to construct models. The performance of a model was evaluated by the correlation coefficient (Rp) and the root mean square error (RMSEP) in the prediction set. Among the models used, the synergy interval PLS (Si-PLS) was found to be superior. The optimal performance by the Si-PLS model for the TSC was Rp = 0.8694, RMSEP = 0.438; the AC was Rp = 0.8097, RMSEP = 0.617; and the pH was Rp = 0.9039, RMSEP = 0.0805. The stability and reliability of the system, as well as the optimal models, were verified using coefficients of variation, most of which were found to be less than 5%. The results suggest this portable system is a promising tool that could be used as an alternative method for rapid monitoring of process parameters during rice wine fermentation.

Fabricating Upconversion Fluorescent Probes for Rapidly Sensing Foodborne Pathogens.

Rare earth-doped upconversion nanoparticles (UCNPs) have promising potential in the field of food safety because of their unique frequency upconverting capability and high detection sensitivity. Here, we report a rapid and sensitive UCNP-based bacterium-sensing strategy using Escherichia coli. Highly fluorescent and water-soluble UCNPs were fabricated and conjugated with antibodies against E. coli for use as fluorescent probes. The E. coli were successively captured by the fluorescent probes. After the captured cell samples were pelleted, the differences in the fluorescence intensities between sample supernatants and the control were observed to increase linearly with E. coli concentration from 42 to 42 × 10(6) colony-forming units (cfu)/mL (R(2) = 0.9802), resulting in a relatively low limit of detection of 10 cfu/mL. Furthermore, the ability of the bioassay to detect E. coli was also confirmed in adulterated meat and milk samples.

Classification of foodborne pathogens using near infrared (NIR) laser scatter imaging system with multivariate calibration.

An optical sensor system, namely NIR laser scatter imaging system, was developed for rapid and noninvasive classification of foodborne pathogens. This developed system was used for images acquisition. The current study is focused on exploring the potential of this system combined with multivariate calibrations in classifying three categories of popular bacteria. Initially, normalization and Zernike moments extraction were performed, and the resultant translation, scale and rotation invariances were applied as the characteristic variables for subsequent discriminant analysis. Both linear (LDA, KNN and PLSDA) and nonlinear (BPANN, SVM and OSELM) pattern recognition methods were employed comparatively for modeling, and optimized by cross validation. Experimental results showed that the performances of nonlinear tools were superior to those of linear tools, especially for OSELM model with 95% discrimination rate in the prediction set. The overall results showed that it is extremely feasible for rapid and noninvasive classifying foodborne pathogens using this developed system combined with appropriate multivariate calibration.