Hyaluronic acid-functionalized DDAB/PLGA nanoparticles for improved oral delivery of magnolol in the treatment of ulcerative colitis.

Dysfunction of the mucosal barrier as well as local inflammation are major challenges in the treatment of ulcerative colitis (UC). Mag, a natural compound derived from traditional Chinese medicine, has been shown to have anti-inflammatory and mucosal protection properties. However, its poor gastrointestinal stability as well as its insufficient accumulation in inflamed colonic lesions limit its potential use as an alternative therapeutic drug in UC. The present research involved the design and preparation of a hybrid nanoparticle system (LPNs) specifically targeting macrophages at the colonic site. This was achieved by electrostatically adsorbing HA onto positively charged lipid-polymer hybrid nanoparticles (HA-LPNs). The prepared HA-LPNs exhibited a rounded morphology and a narrow size distribution. In vitro, the anti-inflammatory efficacy of Mag-HA-LPNs (which control levels of the pro-inflammatory cytokines NO, IL-6 and TNF-α) was assessed in RAW 264.7 cells. Analysis by flow cytometry and fluorescence microscopy demonstrated increased cellular uptake through HA/CD44 interaction. As expected, Mag-HA-LPNs was found to effectively increased colon length and reduced DAI scores in DSS-treated mice. This effect was achieved by regulating the inflammatory cytokines level and promoting the restoration of the colonic mucosal barrier through increased expression of Claudin-1, ZO-1 and Occludin. In this study, we developed an efficient and user-friendly delivery method for the preparation of HA-functionalized PLGA nanoparticles, which are intended for oral delivery of Mag. The findings suggest that these HA-LPNs possess the potential to serve as a promising approach for direct drug delivery to the colon for effective treatment of UC.

Amphotericin B-loaded natural latex dressing for treating Candida albicans wound infections using Galleria mellonella model.

Amphotericin B (AmB) is the gold standard for antifungal drugs. However, AmB systemic administration is restricted because of its side effects. Here, we report AmB loaded in natural rubber latex (NRL), a sustained delivery system with low toxicity, which stimulates angiogenesis, cell adhesion and accelerates wound healing. Physicochemical characterizations showed that AmB did not bind chemically to the polymeric matrix. Electronic and topographical images showed small crystalline aggregates from AmB crystals on the polymer surface. About 56.6% of AmB was released by the NRL in 120 h. However, 33.6% of this antifungal was delivered in the first 24 h due to the presence of AmB on the polymer surface. The biomaterial's excellent hemo- and cytocompatibility with erythrocytes and human dermal fibroblasts (HDF) confirmed its safety for dermal wound application. Antifungal assay against Candida albicans showed that AmB-NRL presented a dose-dependent behavior with an inhibition halo of 30.0 ± 1.0 mm. Galleria mellonella was employed as an in vivo model for C. albicans infection. Survival rates of 60% were observed following the injection of AmB (0.5 mg.mL-1) in G. mellonella larvae infected by C. albicans. Likewise, AmB-NRL (0.5 mg.mL-1) presented survival rates of 40%, inferring antifungal activity against fungus. Thus, NRL adequately acts as an AmB-sustained release matrix, which is an exciting approach, since this antifungal is toxic at high concentrations. Our findings suggest that AmB-NRL is an efficient, safe, and reasonably priced ($0.15) dressing for the treatment of cutaneous fungal infections.

Eco-sustainable coatings based on chitosan, pectin, and lemon essential oil nanoemulsion and their effect on strawberry preservation.

Films and coatings manufactured with bio-based renewable materials, such as biopolymers and essential oils, could be a sustainable and eco-friendly alternative for protecting and preserving agricultural products. In this work, we developed films and coatings from pectin and chitosan to protect strawberries (Fragaria x ananassa Duch.) from spoilage and microbial contamination. We developed three coatings containing equal amounts of glycerol and Sicilian lemon essential oil (LEO) nanoemulsion. We identified seventeen chemicals from LEO by GC-MS chromatogram, including d-limonene, α-Pinene, ß-Pinene, and γ-Terpinene. The pectin and chitosan coatings were further characterized using different physicochemical, mechanical, and biological methods. The films demonstrated satisfactory results in strength and elongation at the perforation as fruit packaging. In addition, the coatings did not influence the weight and firmness of the strawberry pulps. We observed that 100 % essential oil was released in 1440 min resulting from the erosion process. Also, the oil preserved the chemical stability of the films. Antioxidant activity (AA), measured by Electron Paramagnetic Resonance (EPR), showed that the coatings loaded with 2 % LEO nanoemulsion (PC + oil) showed that almost 50 % of AA from LEO nanoemulsion was preserved. The chitosan and the pectin-chitosan coatings (PC + oil) inhibited filamentous fungi and yeast contaminations in strawberries for at least 14 days, showing a relationship between the AA and antimicrobial results.

Efficacy of glucocorticoids, chloroquine and vitamin A on cytokine release syndrome: a network pharmacology study.

OBJECTIVE: To verify the efficacy of glucocorticoids, chloroquine and vitamin A in the treatment of cytokine release syndrome (CRS), and to investigate the underlying mechanisms, based on network pharmacology. METHODS: We used network pharmacology analysis and found 20 co-targeted genes of glucocorticoids, chloroquine, vitamin A and CRS. The pharmacological functions and therapeutic pathways of the genes were analyzed by gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. The candidate naturally bioactive compounds against the key genes were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The anti-inflammatory activity of luteolin was assessed by real-time polymerase chain reaction. RESULTS: Among the 20 co-targeted genes of glucocorticoids, chloroquine and vitamin A, interleukin 10 (IL-10), interleukin 2 (IL-2), interleukin 4 (IL-4) and tumor necrosis factor-α (TNF-α) were the key cytokines against CRS. The key pathway involved in the pharmacological mechanism could be cytokine-cytokine receptor interaction pathway, T cell receptor signaling pathway, Janus Kinase-signal transducer and activator of transcription signaling pathway and phosphatidylinositol 3-kinase-protein kinase B signaling pathway. Luteolin targeted by IL-10, IL-4, IL-2 and TNF-α could be one candidate drug for the treatment of CRS. CONCLUSION: This study comprehensively elucidates the pharmacological mechanism for the treatment of CRS and provides a new method for the discovery of drugs for this disease.

Comparison of guidelines on rectal cancer: exception proves the rule?

The standard of care for early or locally advanced rectal cancer is promoted by multiple clinical practice guidelines globally, but the considerable differences between the guidelines may cause confusion. We compared the latest updated clinical practice guidelines from five professional societies/authorities: National Comprehensive Cancer Network, American Society of Colorectal Surgeons, European Society of Medical Oncology, Chinese National Health Commission, and Chinese Society of Clinical Oncology. Key evidence is discussed for a better understanding of some seemingly contradictory recommendations.

Residue and dissipation kinetics of toosendanin in cabbage, tobacco and soil using IC-ELISA detection.

Toosendanin (TSN), as an important Chinese traditional insecticide, has been registered and commercialized in China. In this report, the residual analytical methods, residue dynamics and final residues of TSN in tobacco, cabbage and soil under field condition were studied by IC-ELISA and HPLC. The sensitivity, precision and repeatability of IC-ELISA method were more suitable in comparison with HPLC for the demand of TSN residue analysis. Using IC-ELISA, the half-lives (t1/2) of TSN were found to be 1.30 days in cabbage, 1.70 days in tabacco and 0.71 days in soil, respectively. At the recommended dose, the final residues of TSN detection by IC-ELISA was 0.009 mg·kg-1 in cabbage and 0.043 mg·kg-1 in tobacco, as well as was not detected in soil. Therefore, TSN is easily degradable, and IC-ELISA could be a convenient and supplemental analytical tool for monitoring TSN residue in crops and environment.

Assessment of sediment capping with zirconium-modified bentonite to intercept phosphorus release from sediments.

Three different types of zirconium-modified bentonites (ZrMBs) including zirconium-modified original bentonite (ZrMOB), zirconium-modified magnesium-pretreated bentonite (ZrMMgB), and zirconium-modified calcium-pretreated bentonite (ZrMCaB) were synthesized and used as active covering materials to suppress the release of phosphorus (P) from sediments. To assess the covering efficiency of ZrMBs to inhibit P release from sediments, we examined the impact of ZrMB covering layer on P mobilization in sediments at different depths as well as the release of P through the interface between sediment and overlying water (SWI) by use of simulating P release control experiments and diffusive gradients in thin films (DGT) technology. The results showed that the amount of soluble reactive P (SRP) in the overlying water greatly decreased after covering with ZrMBs. Moreover, both pore water SRP and DGT-liable P (DGT-P) in the top sediments decreased after capping with ZrMBs. An obvious stratification of DGT-P was observed along the vertical direction after covering with ZrMBs, and static and active layers were found in the top sediment and in the lower sediment directly below the static layer, respectively. Furthermore, ZrMB covering led to the change of P species from easily released P to relatively or very stable P, making P in the top sediment more stable compared to that without ZrMB covering. Besides, an overwhelming majority of P immobilized by ZrMBs is hard to be re-released into the water column in a common environment. Overall, the above results demonstrate that sediment covering with ZrMBs could effectively prevent the transport of SRP from sediments into the overlying water through the SWI, and the control of P transport into the overlying water by ZrMB covering could be mostly due to the immobilization of pore water SRP, DGT-P, and mobile P in the top sediment by ZrMBs.

Analysis of Antineutrophil Cytoplasm Antibody from 118 730 Patients in Tertiary Hospitals in Jiangxi Province, China.

BACKGROUND The discovery of antineutrophil cytoplasm antibody (ANCA) makes the early diagnosis of primary vasculitis possible, and also has important guiding significance for the diagnosis and treatment of secondary vasculitis. This study aimed to investigate the clinical significance of ANCA. MATERIAL AND METHODS ANCA was detected by indirect immunofluorescence assay (IIF), and anti-myeloperoxidase (MPO) antibody, and anti-proteinase 3 (PR3) antibody were detected by ELISA. The results were analyzed retrospectively. RESULTS Among 118 730 patients, a total of 5853 (4.93%) were positive for ANCA. In the positive cases, 3.98% were male and 6.33% were female, with significant differences (χ²=123.38, P<0.01). For ANCA, the department with the highest positive rate (15.06%) was the Department of Rheumatology, followed by 7.78% in the Department of Dermatology, 6.79% in the Department of Nephrology, and 5.72% in the Department of Traditional Chinese Medicine (TCM). Anti-PR3 and cANCA were highly specific in primary vasculitis (P<0.01). Anti-MPO and pANCA had high specificity for other autoimmune diseases (P<0.01). CONCLUSIONS ANCA has important guiding significance for vasculitis-related diseases. Therefore, it is important in the diagnosis and treatment of this disease and has value in clinical practice.

A Prevalence Study of Psychosocial Distress in Adolescents and Young Adults With Cancer.

BACKGROUND: Psychosocial distress is common among cancer patients. Significant associations between coping and social support with distress and quality of life in adult cancer patients have been identified before, but little is known about the interrelationships between distress, medical coping, and social support in adolescents and young adults (AYAs). OBJECTIVE: The aims of this study are to investigate the prevalence of psychological distress in Chinese AYAs with cancer and examine the associations among distress, anxiety and depression, medical coping, and social support in the same population. METHODS: A total of 610 AYA patients were recruited for this study; 551 patients completed the Chinese version of the National Comprehensive Cancer Network Distress Thermometer (DT), the Hospital Anxiety and Depression Scale, the Medical Coping Modes Questionnaire, and the Social Support Rating Scale. RESULTS: The prevalence of psychological distress was 89.1% in Chinese AYAs with cancer. The DT scores were the highest in the 21- to 25-year-old patients; the DT scores were positively correlated with anxiety and depression (P < .01) but negatively correlated with medical coping and social support (P < .01). CONCLUSION: The prevalence of psychological distress in AYA cancer patients was higher than that in the general cancer population. Medical coping and social support can lower the prevalence of psychological distress in AYA cancer patients. IMPLICATIONS FOR PRACTICE: Findings suggest the need for evidence-based intervention strategies to enhance medical coping and social support in AYA cancer patients. Nurses are crucial to implementing psychological interventions in AYA cancer patients.

Glycyrrhizic acid inhibits leukemia cell growth and migration via blocking AKT/mTOR/STAT3 signaling.

Glycyrrhizic acid (GA) is the bioactive compound of licorice and has been used as an herbal medicine because of its anti-viral, anti-cancer, and anti-inflammatory properties. This study was designed to investigate the effects of GA on leukemia cells growth, migration, and the mechanisms underlying the anti-cancer activities of GA. MTT test was used to detect the effect of GA on TF-1 leukemia cell growth. Wound closure assay and Transwell were adopted to assess the effect of GA on TF-1 migration and invasion. Migration and invasion related proteins including AKT and mTOR were detected by western blot assay. We further used western blot and immunofluorescence assay to evaluate the effect of GA on STAT3 phosphorylation in vitro. We also evaluated the anti-tumor effect of GA in TF-1 tumor bearing BALB/c mice model. The present study showed GA significant inhibit of TF-1 proliferation in a dose and time-dependent manner. GA could remarkably inhibit TF-1 cell migration and invasion; meanwhile effectively suppress AKT, mTOR, and STAT3 phosphorylation in TF-1 cells. GA in 100 mg/kg/ could inhibit the tumor growth in vivo and down-regulated AKT, mTOR, and STAT3 phosphorylation in TF-1 tumor tissues. Our findings suggest that GA is a promising therapeutic agent for leukemia that targets the AKT/mTOR/STAT3 pathway.