Transplantation of human induced pluripotent stem cell derived keratinocytes accelerates deep second-degree burn wound healing.

BACKGROUND: Current evidence shows that human induced pluripotent stem cells (hiPSCs) can effectively differentiate into keratinocytes (KCs), but its effect on skin burn healing has not been reported. AIM: To observe the effects of hiPSCs-derived KCs transplantation on skin burn healing in mice and to preliminarily reveal the underlying mechanisms. METHODS: An analysis of differentially expressed genes in burn wounds based on GEO datasets GSE140926, and GSE27186 was established. A differentiation medium containing retinoic acid and bone morphogenetic protein 4 was applied to induce hiPSCs to differentiate into KCs. The expression of KCs marker proteins was detected using immunofluorescence staining. A model of a C57BL/6 mouse with deep cutaneous second-degree burn was created, and then phosphate buffered saline (PBS), hiPSCs-KCs, or hiPSCs-KCs with knockdown of COL7A1 were injected around the wound surface. The wound healing, re-epithelialization, engraftment of hiPSCs-KCs into wounds, proinflammatory factor level, and the NF-κB pathway proteins were assessed by hematoxylin-eosin staining, carboxifluorescein diacetate succinimidyl ester (CFSE) fluorescence staining, enzyme linked immunosorbent assay, and Western blotting on days 3, 7, and 14 after the injection, respectively. Moreover, the effects of COL7A1 knockdown on the proliferation and migration of hiPSCs-KCs were confirmed by immunohistochemistry, EdU, Transwell, and damage repair assays. RESULTS: HiPSCs-KCs could express the hallmark proteins of KCs. COL7A1 was down-regulated in burn wound tissues and highly expressed in hiPSCs-KCs. Transplantation of hiPSCs-KCs into mice with burn wounds resulted in a significant decrease in wound area, an increase in wound re-epithelialization, a decrease in proinflammatory factors content, and an inhibition of NF-κB pathway activation compared to the PBS group. The in vitro assay showed that COL7A1 knockdown could rescue the inhibition of hiPSCs-KCs proliferation and migration, providing further evidence that COL7A1 speeds up burn wound healing by limiting cell proliferation and migration. CONCLUSION: In deep, second-degree burn wounds, COL7A1 can promote KC proliferation and migration while also suppressing the inflammatory response.

[Soil organic carbon density and its influencing factors in croplands with different cultivation years in the Northeastern Ulan Buh Desert, China]. / ä¹Œå °å¸ƒå’Œæ²™æ¼ ä¸œåŒ—éƒ¨ä¸åŒè€•ä½œå¹´é™å†œç”°åœŸå£¤æœ‰æœºç¢³å¯†åº¦åŠå ¶å½±å“å› ç´ .

Understanding the changes and influencing factors of soil organic carbon density (SOCD) during the conversion of uncultivated natural soil to croplands is of great significance for the assessment of carbon sequestration in arid areas. In this study, we compared SOCD in the uncultivated soil and that in croplands with different cultivation years (2-5, 12-15, 25-30, 40-50 years) in the Northeastern Ulan Buh Desert. The change of SOCD and its influencing factors at 0-2 m soil depth during the conversion of uncultivated natural soil to croplands were explored by the method of replacing time with space. The results showed that SOCD at the shallow soil depth (0-0.4 m) in croplands increased continuously with cultivation years, but basically at low levels (0.990-1.983 kg·m-2). The SOCD at deep soil (1.2-2 m) increased in the croplands with longer cultivation years (25-30 and 40-50 years), whereas no obvious change trends in both the croplands with shorter cultivation years (2-5 and 12-15 years) and the uncultivated natural soil. The SOCD at deep soil (1.2-2 m) were relatively large (28.9%-38.6%) of the 0-2 m soil depth of uncultivated natural soil and croplands with different cultivation years. The vertical distribution of SOCD in croplands with different cultivation years were well fitted by quadratic functions (with R2 ranging from 0.757 to 0.972). It was noteworthy that soil clay and silt contents had dominant influences on SOCD at all the soil profile (0-2 m), and that cultivation years mainly contributed to the accumulation of SOC at the shallow soil (0-0.4 m).

A CpG Methylation Classifier to Predict Relapse in Adults with T-Cell Lymphoblastic Lymphoma.

PURPOSE: Adults with T-cell lymphoblastic lymphoma (T-LBL) generally benefit from treatment with acute lymphoblastic leukemia (ALL)-like regimens, but approximately 40% will relapse after such treatment. We evaluated the value of CpG methylation in predicting relapse for adults with T-LBL treated with ALL-like regimens. EXPERIMENTAL DESIGN: A total of 549 adults with T-LBL from 27 medical centers were included in the analysis. Using the Illumina Methylation 850K Beadchip, 44 relapse-related CpGs were identified from 49 T-LBL samples by two algorithms: least absolute shrinkage and selector operation (LASSO) and support vector machine-recursive feature elimination (SVM-RFE). We built a four-CpG classifier using LASSO Cox regression based on association between the methylation level of CpGs and relapse-free survival in the training cohort (n = 160). The four-CpG classifier was validated in the internal testing cohort (n = 68) and independent validation cohort (n = 321). RESULTS: The four-CpG-based classifier discriminated patients with T-LBL at high risk of relapse in the training cohort from those at low risk (P < 0.001). This classifier also showed good predictive value in the internal testing cohort (P < 0.001) and the independent validation cohort (P < 0.001). A nomogram incorporating five independent prognostic factors including the CpG-based classifier, lactate dehydrogenase levels, Eastern Cooperative Oncology Group performance status, central nervous system involvement, and NOTCH1/FBXW7 status showed a significantly higher predictive accuracy than each single variable. Stratification into different subgroups by the nomogram helped identify the subset of patients who most benefited from more intensive chemotherapy and/or sequential hematopoietic stem cell transplantation. CONCLUSIONS: Our four-CpG-based classifier could predict disease relapse in patients with T-LBL, and could be used to guide treatment decision.

A gene-expression-based signature predicts survival in adults with T-cell lymphoblastic lymphoma: a multicenter study.

We aimed to establish a discriminative gene-expression-based classifier to predict survival outcomes of T-cell lymphoblastic lymphoma (T-LBL) patients. After exploring global gene-expression profiles of progressive (n = 22) vs. progression-free (n = 28) T-LBL patients, 43 differentially expressed mRNAs were identified. Then an eleven-gene-based classifier was established using LASSO Cox regression based on NanoString quantification. In the training cohort (n = 169), high-risk patients stratified using the classifier had significantly lower progression-free survival (PFS: hazards ratio 4.123, 95% CI 2.565-6.628; p < 0.001), disease-free survival (DFS: HR 3.148, 95% CI 1.857-5.339; p < 0.001), and overall survival (OS: HR 3.790, 95% CI 2.237-6.423; p < 0.001) compared with low-risk patients. The prognostic accuracy of the classifier was validated in the internal testing (n = 84) and independent validation cohorts (n = 360). A prognostic nomogram consisting of five independent variables including the classifier, lactate dehydrogenase levels, ECOG-PS, central nervous system involvement, and NOTCH1/FBXW7 status showed significantly greater prognostic accuracy than each single variable alone. The addition of a five-miRNA-based signature further enhanced the accuracy of this nomogram. Furthermore, patients with a nomogram score ≥154.2 significantly benefited from the BFM protocol. In conclusion, our nomogram comprising the 11-gene-based classifier may make contributions to individual prognosis prediction and treatment decision-making.

Berberine: A Traditional Natural Product With Novel Biological Activities.

CONTEXT: Having been used for thousands of years to treat gastrointestinal diseases, the natural isoquinoline alkaloid, berberine, has exhibited a wide spectrum of biochemical and pharmacological effects in studies of recent years. OBJECTIVE: The review intended to examine the many novel bioactivities of berberine, including antidiabetic, anticancer, neuroprotective, anti-inflammatory, and anti-atherosclerotic actions. DESIGN: The research team searched the MEDLINE database using PubMed, using different keyword combinations, including berberine AND diabetes, berberine AND cancer, berberine AND (neuron OR brain), berberine AND inflammation, and "berberine AND atherosclerosis to find studies evaluating the various effects exerted berberine. CONCLUSION: Berberine is a promising multipotent agent to combat diabetes, cancer, Alzheimer's disease, and other diseases.

[Hydrochemical Characteristics of Karst Groundwater in the Mountains of Northern Bazhong City, China].

To study the hydrogeochemical characteristics and formation mechanism of groundwater in a karst development transition zone in southern and northern China, 25 groundwater samples were collected from the Shuangfengya area in the northern part of Bazhong City. Descriptive statistics, coefficients of variation, Schoeller diagrams, Sukalev classification, Piper diagrams, and Gibbs and ion scale coefficients were used to analyze the karst water chemistry and distribution characteristics. The main processes controlling the chemical evolution of the groundwater are also discussed. The research shows that the degree of groundwater mineralization in the study area is generally low, with mostly neutral water and alkaline water. There are some differences in groundwater between the northern and southern regions; the anions and cations in the groundwater in the northern area were mainly HCO3-, Ca2+, and Mg2+, with HCO3-Ca·Mg being the main water chemistry type; the anions and cations in the groundwater in the northern area were mainly HCO3-, and Ca2+, and HCO3-Ca was the main water chemistry type. The chemical character of groundwater was controlled by rock weathering and alternate cation adsorption, and evaporation crystallization in the southern region was more significant than in the northern region. Furthermore, rainfall in the northern region had a more significant effect on groundwater geochemistry than in the south. The differences in climate and lithology between the northern and southern region are the dominant factors influencing the differences in hydrochemistry.

Evolution and Dosimetric Analysis of Magnetic Resonance Imaging-Detected Brain Stem Injury After Intensity Modulated Radiation Therapy in Nasopharyngeal Carcinoma.

PURPOSE: To evaluate the evolution of radiation-induced brain stem injury (BSI) in patients with nasopharyngeal carcinoma (NPC) treated with intensity modulated radiation therapy (IMRT) and to identify the critical dosimetric predictors of BSI. METHODS AND MATERIALS: A total of 6288 NPC patients treated with IMRT between 2009 and 2015 were retrospectively reviewed. Among these 6288 patients, 24 had radiation-induced BSI, which manifested as edematous lesions and contrast-enhanced lesions (CLs) on magnetic resonance imaging. Latency, symptoms, and evolution of BSI were assessed. Critical dosimetric predictors of BSI were identified using a penalized regression model with performance evaluated by receiver operating characteristic curve analysis. RESULTS: Median BSI latency was 14.5 months (range, 7.6-37.5 months), and 9 out of 24 patients (37.5%) were clinically symptomatic. Edematous lesions and CLs were both present in all patients. Necrosis was significantly more common in larger CLs (P = .007). After median follow-up of 12.5 months, 13 out of 24 patients (54.2%) had complete remission, and 5 out of 24 patients (20.8%) had partial remission. Remission was unaffected by whether or not symptomatic treatment was given. Maximum point dose (Dmax) was identified as the critical predictor of BSI (area under the receiver operating curve = 0.898), with the optimal cutoff equivalent dose in 2-Gy fractions (D2) being 67.4 Gy (sensitivity = 0.833, 20 out of 24; specificity = 0.835, 5234 out of 6264). Patients with Dmax ≥67.4 Gy (D2) were significantly more likely to develop BSI (odds ratio = 25.29; 95% CI, 8.63-74.14; P < .001) than those with Dmax <67.4 Gy (D2). CONCLUSIONS: In patients with NPC treated with IMRT, BSI generally tends to improve over time. Dmax = 67.4 Gy (D2) appears to be the dose constraint for brain stem, potentially providing clinicians with greater choice and flexibility when balancing the tumor target coverage and brain stem protection. Further studies are needed to validate our findings.

Prognostic and predictive value of a microRNA signature in adults with T-cell lymphoblastic lymphoma.

New prognostic factors are needed to establish indications for haematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) for T-cell lymphoblastic lymphoma (T-LBL) patients. We used microarray to compare T-LBL tissue samples (n = 75) and fetal thymus tissues (n = 20), and identified 35 differentially expressed miRNAs. Using 107 subjects as the training group, we developed a five-miRNA-based classifier to predict patient survival with LASSO Cox regression: lower risk was associated with better prognosis (disease-free survival (DFS): hazard ratio (HR) 4.548, 95% CI 2.433-8.499, p < 0.001; overall survival (OS): HR 5.030, 95% CI 2.407-10.513, p < 0.001). This classifier displayed good performance in the internal testing set (n = 106) and the independent external set (n = 304). High risk was associated with more favorable response to HSCT (DFS: HR 1.675, 95% CI 1.127-2.488, p = 0.011; OS: HR 1.602, 95% CI 1.055-2.433, p = 0.027). When combined with ECOG-PS and/or NOTCH1/FBXW7 status, this classifier had even better prognostic performance in patients receiving HSCT (DFS: HR 2.088, 95% CI 1.290-3.379, p = 0.003; OS: HR 1.996, 95% CI 1.203-3.311, p = 0.007). The five-miRNA classifier may be a useful prognostic biomarker for T-LBL adults, and could identify subjects who could benefit from HSCT.

Role of ADAMTS-12 in Protecting Against Inflammatory Arthritis in Mice By Interacting With and Inactivating Proinflammatory Connective Tissue Growth Factor.

OBJECTIVE: It has been reported that ADAMTS-12 is a susceptibility gene for rheumatoid arthritis (RA) development, and its level is significantly increased in RA patients. In addition, ADAMTS-12 is reported to be required for inflammation in otherwise healthy subjects. This study was undertaken to determine the role of ADAMTS-12 and the underlying mechanisms in the pathogenesis of inflammatory arthritis. METHODS: The collagen-induced arthritis (CIA) model was established in ADAMTS-12-deficient mice and their control littermates to determine the role of ADAMTS-12 in vivo. Micro-computed tomography scanning was used to demonstrate the destruction of the ankle joint; histologic analysis illustrated synovitis, pannus formation, and bone and cartilage destruction; enzyme-linked immunosorbent assay was performed to measure serum levels of inflammatory cytokines; and protein-protein interaction assays were performed to detect the interactions of ADAMTS-12 and its various deletion mutants with connective tissue growth factor (CTGF). RESULTS: Deficiency of ADAMTS-12 led to accelerated inflammatory arthritis in the CIA mouse model. Loss of ADAMTS-12 caused enhanced osteoclastogenesis. In vitro and in vivo protein-protein interaction assays demonstrated that ADAMTS-12 bound and processed CTGF, a previously unrecognized substrate of ADAMTS-12. In addition, deletion of ADAMTS-12 enhanced, while overexpression of ADMATS-12 reduced, CTGF-mediated inflammation. Furthermore, ADAMTS-12 regulation of inflammation was largely lost in CTGF-deficient macrophages. Importantly, blocking of CTGF attenuated elevated inflammatory arthritis seen in the ADAMTS-12-deficient CIA mouse model. CONCLUSION: This study provides evidence that ADAMTS-12 is a critical regulator of inflammatory arthritis and that this is mediated, at least in part, through control of CTGF turnover.

Geographical heterogeneity and inequality of access to improved drinking water supply and sanitation in Nepal.

BACKGROUND: Per United Nations' Sustainable Development Goals, Nepal is aspiring to achieve universal and equitable access to safe and affordable drinking water and provide access to adequate and equitable sanitation for all by 2030. For these goals to be accomplished, it is important to understand the country's geographical heterogeneity and inequality of access to its drinking-water supply and sanitation (WSS) so that resource allocation and disease control can be optimized. We aimed 1) to estimate spatial heterogeneity of access to improved WSS among the overall Nepalese population at a high resolution; 2) to explore inequality within and between relevant Nepalese administrative levels; and 3) to identify the specific administrative areas in greatest need of policy attention. METHODS: We extracted cluster-sample data on the use of the water supply and sanitation that included 10,826 surveyed households from the 2011 Nepal Demographic and Health Survey, then used a Gaussian kernel density estimation with adaptive bandwidths to estimate the distribution of access to improved WSS conditions over a grid at 1 × 1 km. The Gini coefficient was calculated for the measurement of inequality in the distribution of improved WSS; the Theil L measure and Theil T index were applied to account for the decomposition of inequality. RESULTS: 57% of Nepalese had access to improved sanitation (range: 18.1% in Mahottari to 100% in Kathmandu) and 92% to drinking-water (range: 41.7% in Doti to 100% in Bara). The most unequal districts in Gini coefficient among improved sanitation were Saptari, Sindhuli, Banke, Bajura and Achham (range: 0.276 to 0.316); and Sankhuwasabha, Arghakhanchi, Gulmi, Bhojpur, Kathmandu (range: 0.110 to 0.137) among improved drinking-water. Both the Theil L and Theil T showed that within-province inequality was substantially greater than between-province inequality; while within-district inequality was less than between-district inequality. The inequality of several districts was higher than what is calculated by regression of the Gini coefficient and our estimates. CONCLUSIONS: This study showed considerable geographical heterogeneity and inequality not evidenced in previous national statistics. Our findings may be useful in prioritizing resources to reduce inequality and expand the coverage of improved water supply and sanitation in Nepal.

[Effects of drying and wetting cycles induced by tides on net ecosystem exchange of CO2 over a salt marsh in the Yellow River Delta, China.] / 潮汐作用下干湿交替对黄河三角洲盐沼湿地净生态系统CO2交换的影响.

As a unique hydrological characteristic, the tidal action can strongly affect carbon balance in a salt marsh despite their short duration. Using the eddy covariance technique, we measured the net ecosystem CO2 exchange (NEE) and its environmental factors and tidal change over a salt marsh in the Yellow River Delta. It aimed to investigate the effect of tidal process and drying and wetting cycles induced by tides on NEE. The results showed that the tidal process promoted the daytime CO2 uptake, but it didn't clearly affect the nighttime CO2 release. Tidal inundation was a major factor influencing daytime NEE. The diurnal change of NEE showed a distinct U-shaped curve on both drought and wet stages, but not with substantial variation in its amplitude during the drought stage. The drying and wetting cycles enhanced the absorption of daytime CO2. Under drought stage, the mean of the maximum photosynthetic rate (Amax), apparent quantum yield (α) and ecosystem respiration (Reco) were higher than those in wet stage. In addition, the drying and wetting cycles suppressed the nighttime CO2 release from the salt marsh but increased its temperature sensitivity.

A Novel Risk prediction Model for Patients with Combined Hepatocellular-Cholangiocarcinoma.

Backgrounds: Regarding the difficulty of CHC diagnosis and potential adverse outcomes or misuse of clinical therapies, an increasing number of patients have undergone liver transplantation, transcatheter arterial chemoembolization (TACE) or other treatments. Objective: To construct a convenient and reliable risk prediction model for identifying high-risk individuals with combined hepatocellular-cholangiocarcinoma (CHC). Methods: 3369 patients who underwent surgical resection for liver cancer at Zhongshan Hospital were enrolled in this study. The epidemiological and clinical characteristics of the patients were collected at the time of tumor diagnosis. Variables (P <0.25 in the univariate analyses) were evaluated using backward stepwise method. A receiver operating characteristic (ROC) curve was used to assess model discrimination. Calibration was performed using the Hosmer-Lemeshow test and a calibration curve. Internal validation was performed using a bootstrapping approach. Results: Among the entire study population, 250 patients (7.42%) were pathologically defined with CHC. Age, HBcAb, red blood cells (RBC), blood urea nitrogen (BUN), AFP, CEA and portal vein tumor thrombus (PVTT) were included in the final risk prediction model (area under the curve, 0.69; 95% confidence interval, 0.51-0.77). Bootstrapping validation presented negligible optimism. When the risk threshold of the prediction model was set at 20%, 2.73% of the patients diagnosed with liver cancer would be diagnosed definitely, which could identify CHC patients with 12.40% sensitivity, 98.04% specificity, and a positive predictive value of 33.70%. Conclusions: Herein, the study established a risk prediction model which incorporates the clinical risk predictors and CT/MRI-presented PVTT status that could be adopted to facilitate the diagnosis of CHC patients preoperatively.

Comparative Proteomic Analysis of the Effect of the Four-Herb Chinese Medicine ANBP on Promoting Mouse Skin Wound Healing.

Traditional Chinese medicine has great potential to improve wound healing. ANBP, the mixture of 4 Chinese herbs- Agrimoniapilosa, Nelumbonucifera, Boswelliacarteri, and Pollen typhae-is effective in trauma treatment while its mechanism is still elusive. In this study, quantitative proteomics and bioinformatics analyses were performed to decipher the possible roles of ANBP in accelerated wound healing of mouse skin. Among all 3171 identified proteins, 90, 71, 80, and 140 proteins were found to be differently expressed in 6 hours, 3 days, 7 days, and 14 days ANBP-treated tissues compared with corresponding control tissues, respectively. The result showed that different biological processes and pathways were activated at different healing stages. At the early healing stage, ANBP treatment mainly affected several biological processes, including immune and defense response, vascular system restoration, hemostasis and coagulation regulation, lipid metabolism and signal transduction, while muscle tissue, hair, epidermis, extracellular matrix and tissue remodeling related activities were the major events in ANBP promoted later wound healing. This is the first quantitative proteome study of ANBP-treated wound tissues, which provide a new perspective for the mechanism of ANBP accelerated wound healing and is of guiding significance for clinical application of ANBP in trauma disorders cure.

[Chemical constituents from Impatiens pritzllii var. hupehensis].

Eight compounds were isolated from the 50% ethanol extract of Impatiens pritzllii var.hupehensis through various column chromatography methods including silica gel, Sephadex LH-20, and preparative HPLC. Their structures were elucidated as 2,6-dimethyl-2-vinyl-2,3,4,7-tetrahydrooxepine(1), 1,3,6-trihydroxy-7-methyl-anthraquinone(2),4-hydroxybenzaldehyde(3),4-(3-methoxy-4-hydroxyphenyl)-2-butanone(4), podophyllotoxin(5),scopoletin(6), α-spinasterol(7) and 3-O-ß-D-glucopyranosyl-α-spinasterol(8) based on the NMR and MS spectral data. Compound 1 is new compound and compounds 2-8 are isolated from this plant for the first time.

Report: Cytotoxic flavonoids from the young twigs and leaves of Caesalpinia bonduc (Linn) Roxb.

The extraction, fractionation and recognition of flavonoids from the ethanolic extract of young twigs and leaves of C. bonduc were carried out. In addition, cytotoxic study of the flavonoids on two cancer cell lines, BGC-823 and HeLa was carried our using sulphorhodamine B assay. Seven flavonoids, six of which are being reported for the first time in this plant, were isolated. Their structures were identified by MS and NMR spectroscopic methods. Petroleum ether, ethyl acetate and water fractions exhibited moderate cytotoxic activity against HeLa cells. Five compounds showed cytotoxic activity against HeLa cell in comparison with Paclitaxel, while only one compound showed a good degree of cytotoxic activity against BGC-823 cell in comparison to Paclitaxel. The results obtained showed a structure - activity relationship.

Chemical constituents from stems and leaves of Micromelum integerrimum.

A new benzene derivative microintegerrin C (1) and a new norsesquiterpenoid microintegerrin D (2), along with six known compounds (3-8), were isolated and identified from stems and leaves of Micromelum integerrimum by various chromatographies such as silica gel, Sephadex LH-20, RP-18 column chromatography and HPLC. Their structures were mainly identified based on the spectral data analysis such as 1D-, 2D-NMR and HR-EI-MS. All known compounds were isolated from this plant for the first time.

Effects of the Four-Herb Compound ANBP on Wound Healing Promotion in Diabetic Mice.

Wound healing is a troublesome problem in diabetic patients. Besides, there is also an increased risk of postsurgical wound complications for diabetic patient. It has been revealed that traditional Chinese medicine may promote healing and inhibit scar formation, while the changes of morphology and physiology of wounds on such medicine treatment still remain elusive. In this study, we first used the ultralow temperature preparation method to produce mixed superfine powder from Agrimonia pilosa (A), Nelumbo nucifera (N), Boswellia carteri (B), and Pollen typhae (P), named as ANBP. Applying ANBP on 40 streptozotocin (STZ)-induced diabetic C57BL/6 mice (4-6 weeks, 20 ± 2 g), we observed that the wound healing process was accelerated and the wound healing time was shortened (14 days, P < .05). Pathological observation using hematoxylin-eosin staining indicated that inflammatory cells were reduced (P < .05) while the thickness of granulation tissue and length of epithelial tongue were increased (P < .05). The vascular density was increased on 7 and 14 days after ANBP treatment. Masson and Sirius red staining showed that, at the early stage of trauma, the expressions of Col I and Col III, especially Col III, were increased in the ANBP group (P < .05). Studies in vitro demonstrated that tubular formation was significantly increased after ANBP treatment on human vascular endothelial cells in a dose-dependent way. Taken together, our studies revealed that ANBP treatment could accelerate wound healing, promote vascularization, and inhibit inflammation, suggesting the potential clinic application of ANBP for diabetes mellitus and refractory wounds.

The four-herb Chinese medicine ANBP enhances wound healing and inhibits scar formation via bidirectional regulation of transformation growth factor pathway.

The four-herb Chinese medicine ANBP is a pulverized mixture of four herbs including Agrimonia Eupatoria (A), Nelumbo Nucifera Gaertn (N), Boswellia Carteri (B) and Pollen Typhae Angustifoliae (P). The combination of the four herbs was first described in Chinese canonical medicine about 2000 years ago for treatment of various trauma disorders, such as hemostasis, antiinflammatory, analgesia, and wound healing, etc. However, the precise mechanisms of ANBP are still unclear. In our study, using rabbit ear hypertrophic scar models of full-thickness skin defect, we showed that local ANBP treatment not only significantly enhanced wound healing by relieving inflammation, increasing formation of granulation tissue and accelerating re-epithelialization, but also reduced scar formation by decreasing collagen production, protuberant height and volume of scars, and increasing collagen maturity. We demonstrated that these effects of ANBP are associated with transforming growth factor (TGF)-ß1-mediated signalling pathways through Smad-dependent pathways. ANBP treatment significantly increased expression of TGF-ß1 and Smad2/3 mRNA at the early stage of wound healing, and led to markedly decrease expression of TGF-ß1 and Smad2/3 compared with the control group after 14 days post-wounding. Taken together, our results defined a bidirectional regulation role of ANBP for TGF-ß1/Smad pathway in promoting wound healing and alleviating scar formation, which may be an effective therapy for human wounds at the earliest stage.

Two new phenylpropanoids from Micromelum integerrimum.

AIM: To investigate the chemical and bioactive constituents from the stems and leaves of Micromelum integerrimum. METHOD: The chemical constituents were isolated and purified by silica gel, Sephadex LH-20, and HPLC. Their structures were mainly elucidated on the basis of extensive 1D- and 2D-NMR spectroscopy and mass spectrometry. Their cytotoxicity and antimicrobial activities were tested by the SRB and turbidimetric methods, respectively. RESULTS: Two new phenylpropanoids and two known coumarins were obtained, and their structures were identified as microintegerrin A (1), microintegerrin B (2), scopoletin (3), and scopolin (4). All of the compounds were tested for their cytotoxicity against three cancer cell lines (HeLa, A549, and BGC-823) and for antimicrobial activity against the fungus Candida albicans and the bacterium Staphylococcus aureus. CONCLUSION: Two new phenylpropanoids 1 and 2 were isolated and identified from the stems and leaves of M. intgerrimum. None of the compounds showed cytotoxic or antimicrobial activity at the tested concentration of 20 µg·mL(-1).

New dicyclopeptides from Dianthus chinensis.

One new dicyclopeptide cyclo-(L-N-methyl Glu-L-N-methyl Glu) (1), together with one new natural dicyclopeptide cyclo-(L-methyl Glu ester-L-methyl Glu ester) (2), and two known dicyclopeptides cyclo-(L-methyl Glu ester-L-Glu) (3), and cyclo-(L-Glu-L-Glu) (4), were isolated from the aerial parts of Dianthus chinensis L. Their structures were determined by spectroscopic analyses and chemical methods.