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

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

Study on the photosynthetic growth characters in Cimicifuga dahurica (Turcz.) Maxim under different supplemental light environments.

Cimicifuga dahurica (C. dahurica) is an important medicinal plant in the northern region of China. The best supplemental light environment helps plant growth, development, and metabolism. In this study, we used two-year-old seedlings as experimental materials. The white light as the control (CK). The different ratios of red (R) and blue (B) combined light were supplemented (T1, 2R: 1B, 255.37 µmol m-2·s-1; T2, 3R: 1B, 279.69 µmol m-2·s-1; T3, 7R: 1B, 211.16 µmol m-2·s-1). The growth characteristics, photosynthetic pigment content, photosynthesis and chlorophyll fluorescence parameters, and primary metabolite content were studied in seedlings. The results showed that: 1) The fresh weight from shoot, root, and total fresh weight were significantly (P < 0.05) increased under T2 and T3 treatment. 2) The contents of chlorophyll a (Chl a), chlorophyll b (Chl b), and total chlorophyll (Chl) were significantly (P < 0.05) increased under T2 treatment, and carotenoid (car) content was reduced. 3) The photochemical quenching (qP), the actual photosynthetic efficiency of PSII (Y(II)), and the photosynthetic electron transfer rate (ETR) from leaves were significantly (P < 0.05) increased under T1 treatment. The Net photosynthetic rate (Pn), stomatal conductance (Gs), intercellular CO2 concentration (Ci), and transpiration rate (Tr) were significantly (P < 0.05) increased under T2 and T3 treatments. 4) A total of 52 primary metabolites were detected in C. dahurica leaves. Compared with CK, 14, 15, and 18 differential metabolites were screened under T1, T2, and T3 treatments. In addition, D-xylose, D-glucose, glycerol, glycolic acid, and succinic acid were significantly (P < 0.05) accumulated under the T2 treatment, which could regulate the TCA cycle metabolism pathway. The correlation analysis suggested that plant growth was promoted by regulating the change of D-mannose content in galactinol metabolism and amino sugar and nucleotide sugar metabolism. In summary, the growth of C. dahurica was improved under T2 treatment.

Intramuscular delivery of a naked DNA plasmid encoding proinsulin and pancreatic regenerating III protein ameliorates type 1 diabetes mellitus.

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by inflammation of pancreatic islets and destruction of ß cells. Up to now, there is still no cure for this devastating disease and alternative approach should be developed. To explore a novel gene therapy strategy combining immunotherapy and ß cell regeneration, we constructed a non-viral plasmid encoding proinsulin (PI) and pancreatic regenerating (Reg) III protein (pReg/PI). Therapeutic potentials of this plasmid for T1DM were investigated. Intramuscular delivery of pReg/PI resulted in a significant reduction in hyperglycemia and diabetes incidence, with an increased insulin contents in the serum of T1DM mice model induced by STZ. Treatment with pReg/PI also restored the balance of Th1/Th2 cytokines and expanded CD4(+)CD25(+)Foxp3(+) T regulatory cells, which may attribute to the establishment of self-immune tolerance. Additionally, in comparison to the mice treated with empty vector pBudCE4.1 (pBud), attenuated insulitis and apoptosis achieved by inhibiting activation of NF-κB in the pancreas of pReg/PI treated mice were observed. In summary, these results indicate that intramuscular delivery of pReg/PI distinctly ameliorated STZ-induced T1DM by reconstructing the immunological self-tolerance and promoting the regeneration of ß cells, which might be served as a promising candidate for the gene therapy of T1DM.

Immunosuppressive constituents from Urtica dentata Hand.

A novel biscoumarin, 6,6',7,7'-tetramethoxyl-8,8'-biscoumarin (1), was isolated from the ethyl acetate extract of Urtica dentata Hand, together with five known compounds named as 7,7'-dihydroxy-6,6'-dimethoxy-8,8'-biscoumarin (2), 7,7'-dimethoxy-6,6'-biscoumarin (3), scoparone (4), vanillic acid (5), and daucosterol (6). Structures of the isolated compounds were elucidated on the basis of spectroscopic analysis including 2D NMR experiments. Compounds 1 and 2 were confirmed to be a rare carbon-carbon linked symmetrical biscoumarin. Compounds 1-4, especially 1 (IC(50) = 8.18 x 10(- 5) mol/l), showed potent immunosuppressive activities as determined by the Cell Counting Kit-8 assay for lymphocyte proliferation. Also, in the FACS analysis, 1 (IC(50) = 5.19 x 10(- 4) mol/l) promoted the differentiation of CD4(+)CD25(+)Foxp3(+) T regulatory cells distinctly compared to the normal control. Thus, 1 possessed specific immunosuppressive property by eliciting T regulatory cells, which may provide a potential treatment strategy for autoimmune diseases.

[Recombination of RegIII-proinsulin-pBudCE4.1 plasmid and its therapeutic effect on STZ-induced type 1 diabetes mellitus].

The aim of this study is to investigate the therapeutic effect of RegIII-proinsulin-pBudCE4.1 plasmid on streptozotocin (STZ)-induced type 1 diabetes mellitus and its underlying mechanisms. The model of type 1 diabetes mellitus was established by intraperitoneal injections of STZ (40 mg kg(-1)) to Balb/c mice for five consecutive days. Then, ten type 1 diabetic mice were intramuscularly injected with 100 microg RegIII-proinsulin-pBudCE4.1 plasmid for 4 weeks (one time/week) and the blood glucose levels were monitored every week; whereas another ten diabetic mice served as negative control group were injected with pBudCE4.1 vector at the same dose. Normal control and model control mice were treated with normal saline at identical volume under the same way. Western blotting, MTT assay, ELISA, HE staining and Tunel assay were applied to explore the underlying mechanisms. Results showed that RegIII-proinsulin-pBudCE4.1 plasmid ameliorated the hyperglycemia symptoms in diabetic mouse remarkably. It induced an immunological tolerance state in type 1 diabetic mice by inhibiting the proliferation of splenic lymphocytes and recovering Th1/Th2 balance evidenced by MTT and ELISA analysis. Furthermore, it elevated insulin concentration in the serum of type 1 diabetic mice and promoted the regeneration of beta cells supported by the results of HE staining and Tunel assay. In conclusion, RegIII-proinsulin-pBudCE4.1 plasmid possesses powerful anti-diabetic ability, which may be involved in the inducing of immunological tolerance and enhancing beta cells recovery.

Association of meteorological factors with pediatric acute appendicitis in China: A 7-year retrospective analysis.

Acute appendicitis (AA) affects between 7% and 8% of the world population and is one of the most common general surgical emergencies. The concept of seasonal patterns in the incidence of AA remains controversial. Thus, this study aimed to investigate whether meteorological factors are related to variations in the rate of pediatric AA cases at the Children's Hospital in Chongqing, China.In total, in this retrospective survey, 3436 children younger than 18 years who had been hospitalized with AA from January 1, 2008 to December 31, 2013 were enrolled, and the meteorological factors during this period were collected.Patients with AA showed a male/female ratio of 1.81:1; the highest incidence age ranged from 6 to 12 years old (P < .0001). The highest incidences of pediatric AA occurred in summer and autumn, with a peak in September and a trough in February. Pearson correlation analysis showed that the monthly mean temperature (r = 0.357, P = .001), monthly mean relative humidity (r = -0.357, P = .001), and monthly mean sunshine duration (r = 0.235, P = -0.031) were relatively weak correlated with pediatric AA. Multiple linear regression analysis indicated that pediatric AA occurrence was positively affected by monthly mean temperature (P < .0001) and negatively affected by monthly mean humidity (P < .0001) and monthly sum of sunshine (P < .0001), while monthly mean air pressure (P = .092), monthly wind speed (P = .143) and monthly precipitation (P = .297) were marginally associated with pediatric AA.Pediatric AA is associated with climatic factors. Specifically, pediatric AA is more likely related to the following meteorological conditions of: high temperature (20 °C-30 °C), low humidity, and less sunshine.

An Open-label, Self-control, Prospective Study on Cognitive Function, Academic Performance, and Tolerability of Osmotic-release Oral System Methylphenidate in Children with Attention-deficit Hyperactivity Disorder.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is the most common mental and behavioral disorder in school-aged children. This study evaluated the effect of osmotic-release oral system (OROS) methylphenidate (MPH) on cognitive function and academic performance of Chinese school-aged children with ADHD. METHODS: This 12-week, prospective, multicenter, open-label, self-controlled study enrolled 153 Chinese school-aged children with ADHD and 41 non-ADHD children. Children with ADHD were treated with once-daily OROS-MPH (18 mg, 36 mg, or 54 mg). The primary endpoints were Inattention/Overactivity (I/O) with Aggression Conners Behavior Rating Scale (IOWA) and Digit Span Test at week 12 compared with baseline. Secondary endpoints included opposition/defiant (O/D) subscale of IOWA, Clinical Global Impression (CGI), Coding Test, Stroop Color-word Test, Wisconsin Card Sorting Test (WCST), academic performance on teacher-rated school examinations, and safety at week 12 compared with baseline. Both non-ADHD and ADHD children received the same frequency of cognitive operational test to avoid the possible bias caused by training. RESULTS: A total of 128 patients were evaluated with cognitive assessments. The OROS-MPH treatment significantly improved IOWA Conners I/O subscale scores at week 12 (3.8 ± 2.3) versus baseline (10.0 ± 2.4; P < 0.0001). Digit Span Test scores improved significantly (P < 0.0001) with a high remission rate (81.1%) at week 12 versus baseline. A significant (P < 0.0001) improvement was observed in O/D subscale of IOWA, CGI, Coding Test, Stroop Color-word Test, WCST, and academic performance at week 12 versus baseline. Very few practice-related improvements were noticed in the non-ADHD group at week 12 compared with baseline. No serious adverse events and deaths were reported during the study. CONCLUSIONS: The OROS-MPH treatment effectively controlled symptoms of ADHD and significantly improved academic performance and cognitive function of Chinese school-aged children with ADHD. The treatment was found to be safe and generally well-tolerated over 12 weeks. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01933880; http://clinicaltrials.gov/ct2/show/NCT01933880?term=CONCERTAATT4099&rank=1.

[Duration of breastfeeding and its relevant influencing factors on under 2-years-old in rural areas of 10 provinces in China].

OBJECTIVE: To understand the current status and relevant factors influencing the duration of breastfeeding in rural areas in China. METHODS: Children under two years old were selected as subjects from the study on "Physical growth among the under 7-years-old children from the rural areas of ten provinces in China in 2006". Kaplan-Meier method was used to estimate the survival curves and Cox multivariate stepwise regression was used to identify the relevant factors on the duration of breastfeeding. RESULTS: Median of the duration for breastfeeding was 12 months in rural areas of 10 provinces in China. Results of this study suggested that factors as sex, birth order, areas of residency, nationality, initiation of formula, parents' education levels, maternal services and family income were correlated with the duration of breastfeeding. CONCLUSION: Duration of breastfeeding among rural children under 2-years of age was short in the 10 provinces of China. Factors as level of education, residential areas and family income of the parents as well as sex of the children were correlated with the duration of breastfeeding. Intervention program should be implemented to improve the current status on breastfeeding.

beta cell protecting and immunomodulatory activities of Paecilomyces Hepiali Chen mycelium in STZ induced T1DM mice.

The anti-hyperglycemic and immunomodulatory activities of the ethanol extract from Paecilomyces Hepiali Chen (PHC), a Chinese medicine, were investigated in streptozotocin-induced type 1 diabetic (T1DM) mice. Male Balb/c mice, which were i.p. injected with streptozotocin (STZ, 50 mg/kg, for 5 consecutive days) on Day 7, were orally administered saline (the normal control and diabetic control group), Metformin (60 mg/kg, b.w., positive group), or the extract (100 mg/kg, b.w., PHC prevention group) from Day 1 to Day 28, Mice i.p. injected with streptozotocin (STZ, 50 mg/kg, b.w.) for 5 consecutive days prior to PHC treatment (100 mg/kg, b.w.) were used as the PHC treatment group. The effects of PHC on postprandial blood glucose concentrations, plasmatic insulin levels, morphology of pancreatic beta cells and CD4(+) T cells proliferation after 28-day treatment were monitored. Results showed that PHC administered 6 days before STZ induction of diabetes in mice significantly decreased blood glucose level (p < 0.01). An increase of insulin level was also observed as compared to those in the diabetic control group (p < 0.01). In addition, fewer inflammatory cells infiltrated the pancreatic islet and fewer beta cells death by apoptosis within the inflamed islets were observed. More importantly, the CD4(+) T cell proliferation was remarkably attenuated ex vivo in mice preventively treated with PHC (p < 0.01). In comparison to the PHC prevention group, no significant hypoglycemia, changes of insulin level and beta cell protection were observed in mice treated with PHC after STZ administration. Our findings demonstrated that preventive administration of PHC protected beta cells from apoptosis in type 1 diabetes induced by STZ, and the underlying mechanism may be involved in suppressing CD4(+) T cells reaction, reducing inflammatory cells infiltration and protecting beta cell apoptosis in pancreatic islet.

Immunosuppressive effects of an ethyl acetate extract from Urtica dentata Hand on skin allograft rejection.

AIM OF THE STUDY: To investigate the immunosuppressive effects of HPLC qualitied ethyl acetate extract (EAE) from Urtica dentate Hand on skin allograft rejection in a murine model. MATERIALS AND METHODS: Allo-skin transplantation model was established by placing skin allograft of C57BL/6 mice in the wound bed which was on the back of Balb/c mice. We used FACS to study the effects of EAE on dendritic cells (DCs) maturation and CD4(+)CD25(+)T regulatory cells (Tregs) differentiation. We also studied spleen lymphocyte proliferation and T-bet gene expression in DCs. Concentration of Th1/Th2 cytokines was monitored as markers of Th1/Th2 responses by ELISA. RESULTS: A significant prolongation of skin allografts survival was observed as a dose-dependent manner in the animals treated with EAE. By FACS, we found that treatment with EAE (200 mg kg(-1)) resulted in an immature statement of DCs and stimulated the differentiation of CD4(+)CD25(+)Tregs. Additionally, the expression of T-bet gene and the proliferation of spleen lymphocytes were efficiently abated in EAE treated mice. Comparing to the model control, EAE-treated recipients showed a significant down-regulation (P<0.01) of Th1 cytokines (IL-2, IFN-gamma) and an obviously increase (P<0.01) of Th2 cytokine (IL-10) in the serum, which presented in a dose-related way. CONCLUSIONS: The anti-allograft rejection effect of EAE by enhancing CD4(+)CD25(+)Tregs differentiation and sustaining DCs immaturation makes EAE to be a possible choice for treating autoimmune diseases in a way of inducing a stable immunological tolerance state.