A STUDY OF JOHN BERRYMAN'S DREAM SONGS

Ph.DDOCTOR OF PHILOSOPH

Evaluation of Juglans regia L., root for wound healing via antioxidant, antimicrobial and anti-inflammatory activity

304-311The burden of the management of problematic skin wounds characterized by a compromised skin barrier is growing rapidly. There is an urgent requirement for efficient mechanism-based treatments and more efficacious drug delivery systems. The present study was aimed to examine the wound healing potential of Juglans regia L. root (JR) in rats by incision and excision wound methods via the anti-inflammatory, antioxidant and antimicrobial activities. We have used tensile strength and biochemical parameters for studying the wound healing properties of JR by incision wound methodology. The anti-inflammatory effect was assessed by the measurement of paw edema in carrageenan-induced inflammation in rats. The wound contraction area, antioxidant status, and antimicrobial studies were exhausted excision wound methodology. There was a significant decrease in percent inhibition of paw edema (0.63 ± 0.03 to 0.33 ± 0.02 after 24 h) with an increase in JR concentration. Tensile strength and hydroxyproline level of different concentrations (1, 2.5, 5, and 10% w/w) of JR ointment treated groups were found significantly (P <0.001) comparable to the reference group. Moreover, JR showed significant antimicrobial and antioxidant properties, by its ability to increase antioxidant and antimicrobial levels. In conclusion, the overall results obtained in this study clarify that JR inhibits paw edema and accelerates cutaneous wound healing

In vitro and in vivo targeted delivery of IL-10 interfering RNA by JC virus-like particles

<p>Abstract</p> <p>Background</p> <p>RNA interference (RNAi) is a powerful tool to silence gene expression post-transcriptionally. Delivering sequences of RNAi <it>in vivo </it>remains a problem. The aim of this study was to use JC virus (JCV) virus-like particles (VLPs) as a vector for delivering RNAi in silencing the cytokine gene of IL-10.</p> <p>Methods</p> <p>JCV VLPs were generated by recombinant JCV VP1 protein in yeast expression system. DNA fragment containing IL-10 shRNA was packaged into VLPs by osmotic shock.</p> <p>Results</p> <p>In RAW 264.7 cells, IL-10 shRNA was found to reduce IL-10 expression by 85 to 89%, as compared with VLPs alone. IL-10 shRNA did not cross-react with TNF-alpha mRNA or influence the expression of TNF-alpha. In BALB/c mice IL-10 shRNA could reduce 95% of IL-10 secretion. Surprisingly, it also down regulated TNF-alpha expression.</p> <p>Conclusions</p> <p>We show for the first time that JCV VLPs empty capsids are competent vectors to deliver RNAi and are nontoxic to cells, suggesting that JCV VLPs is an efficient agent to deliver RNAi in both murine macrophage cells and BALB/c mice. This system provides an efficient means for delivering the RNAi for gene therapy purposes.</p

Targeting PELP1 Attenuates Angiogenesis and Enhances Chemotherapy Efficiency in Colorectal Cancer

SIMPLE SUMMARY: Excessive angiogenesis is a distinct feature of colorectal cancer (CRC) and plays a pivotal role in tumor development and metastasis. Therefore, it is essential to clarify the underlying mechanism of angiogenesis. In this study, we found that the level of proline-, glutamic acid, and leucine-rich protein 1 (PELP1) was positively correlated with microvessel density (MVD). In vitro and in vivo assays further showed PELP1 regulated angiogenesis via the Signal transducer and activator of transcription 3 (STAT3)/Vascular endothelial growth factor (VEGFA). Notably, we found that inhibition of PELP1 enhanced the efficacy of chemotherapy due to vascular normalization. Thus, targeting of PELP1 may be a potentially therapeutic strategy for CRC. ABSTRACT: Abnormal angiogenesis is one of the important hallmarks of colorectal cancer as well as other solid tumors. Optimally, anti-angiogenesis therapy could restrain malignant angiogenesis to control tumor expansion. PELP1 is as a scaffolding oncogenic protein in a variety of cancer types, but its involvement in angiogenesis is unknown. In this study, PELP1 was found to be abnormally upregulated and highly coincidental with increased MVD in CRC. Further, treatment with conditioned medium (CM) from PELP1 knockdown CRC cells remarkably arrested the function of human umbilical vein endothelial cells (HUVECs) compared to those treated with CM from wildtype cells. Mechanistically, the STAT3/VEGFA axis was found to mediate PELP1-induced angiogenetic phenotypes of HUVECs. Moreover, suppression of PELP1 reduced tumor growth and angiogenesis in vivo accompanied by inactivation of STAT3/VEGFA pathway. Notably, in vivo, PELP1 suppression could enhance the efficacy of chemotherapy, which is caused by the normalization of vessels. Collectively, our findings provide a preclinical proof of concept that targeting PELP1 to decrease STAT3/VEGFA-mediated angiogenesis and improve responses to chemotherapy due to normalization of vessels. Given the newly defined contribution to angiogenesis of PELP1, targeting PELP1 may be a potentially ideal therapeutic strategy for CRC as well as other solid tumors

Determinants of Developing Stroke Among Low-Income, Rural Residents: A 27-Year Population-Based, Prospective Cohort Study in Northern China

Although strokes are the leading cause of death and disability in many countries, China still lacks long-term monitoring data on stroke incidence and risk factors. This study explored stroke risk factors in a low-income, rural population in China. The study population was derived from the Tianjin Brain Study, a population-based stroke monitoring study that began in 1985. This study documented the demographic characteristics, past medical histories, and personal lifestyles of the study participants. In addition, physical examinations, including measurements of blood pressure (BP), height, and weight, were performed. Hazard ratios (HRs) were estimated for the risk factors for all subtypes of stroke using multivariate Cox regression analyses. During the study with mean following-up time of 23.16 years, 3906 individuals were recruited at baseline, and during 27 years of follow-up, 638 strokes were documented. The multivariate Cox regression analyses revealed a positive correlation between age and stroke incidence. Limited education was associated with a 1.9-fold increase in stroke risk (lowest vs. highest education level). Stroke risk was higher among former smokers than among current smokers (HR, 1.8 vs. 1.6; both, P &lt; 0.05). Moreover, stroke risk was significantly associated with sex (HR, 1.8), former alcohol drinking (HR, 2.7), baseline hypertension (HR, 3.1), and overweight (HR, 1.3). In conclusion, this study identified uncontrollable (sex and age) and controllable (education, smoking, alcohol drinking, hypertension, and overweight) risk factors for stroke in a low-income, rural population in China. Therefore, it is critical to control BP and weight effectively, advocate cessation of smoking/alcohol drinking, and enhance the education level in this population to prevent increase in the burden of stroke in China

Detection and analysis of human papillomavirus (HPV) DNA in breast cancer patients by an effective method of HPV capture

Despite an increase in the number of molecular epidemiological studies conducted in recent years to evaluate the association between human papillomavirus (HPV) and the risk of breast carcinoma, these studies remain inconclusive. Here we aim to detect HPV DNA in various tissues from patients with breast carcinoma using the method of HPV capture combined with massive paralleled sequencing (MPS). To validate the confidence of our methods, 15 cervical cancer samples were tested by PCR and the new method. Results showed that there was 100% consistence between the two methods.DNA from peripheral blood, tumor tissue, adjacent lymph nodes and adjacent normal tissue were collected from seven malignant breast cancer patients, and HPV type 16(HPV16) was detected in 1/7, 1/7, 1/7and 1/7 of patients respectively. Peripheral blood, tumor tissue and adjacent normal tissue were also collected from two patients with benign breast tumor, and 1/2, 2/2 and 2/2 was detected to have HPV16 DNA respectively. MPS metrics including mapping ratio, coverage, depth and SNVs were provided to characterize HPV in samples. The average coverage was 69% and 61.2% for malignant and benign samples respectively. 126 SNVs were identified in all 9 samples. The maximum number of SNVs was located in the gene of E2 and E4 among all samples. Our study not only provided an efficient method to capture HPV DNA, but detected the SNVS, coverage, SNV type and depth. The finding has provided further clue of association between HPV16 and breast cancer

Reflective plasmonic color filters based on lithographically patterned silver nanorod arrays

10.1039/c3nr01419cNanoscale5146243-624

OsWRKY45 alleles play different roles in abscisic acid signalling and salt stress tolerance but similar roles in drought and cold tolerance in rice

Although allelic diversity of genes has been shown to contribute to many phenotypic variations associated with different physiological processes in plants, information on allelic diversity of abiotic stress-responsive genes is limited. Here it is shown that the alleles OsWRKY45-1 and OsWRKY45-2 play different roles in abscisic acid (ABA) signalling and salt stress adaptation in rice. The two alleles had different transcriptional responses to ABA and salt stresses. OsWRKY45-1-overexpressing lines showed reduced ABA sensitivity, whereas OsWRKY45-1-knockout lines showed increased ABA sensitivity. OsWRKY45-1 transgenic plants showed no obvious difference from negative controls in response to salt stress. In contrast, OsWRKY45-2-overexpressing lines showed increased ABA sensitivity and reduced salt stress tolerance, and OsWRKY45-2-suppressing lines showed reduced ABA sensitivity and increased salt stress tolerance. OsWRKY45-1 and OsWRKY45-2 transgenic plants showed differential expression of a set of ABA- and abiotic stress-responsive genes, but they showed similar responses to cold and drought stresses. These results suggest that OsWRKY45-1 negatively and OsWRKY45-2 positively regulates ABA signalling and, in addition, OsWRKY45-2 but not OsWRKY45-1 negatively regulates rice response to salt stress. The different roles of the two alleles in ABA signalling and salt stress may be due to their transcriptional mediation of different signalling pathways

Crystal Structure of EHEC Intimin: Insights into the Complementarity between EPEC and EHEC

Enterohaemorrhagic E. coli (EHEC) O157:H7 is a primary food-borne bacterial pathogen capable of causing life-threatening human infections which poses a serious challenge to public health worldwide. Intimin, the bacterial outer-membrane protein, plays a key role in the initiating process of EHEC infection. This activity is dependent upon translocation of the intimin receptor (Tir), the intimin binding partner of the bacteria-encoded host cell surface protein. Intimin has attracted considerable attention due to its potential function as an antibacterial drug target. Here, we report the crystal structure of the Tir-binding domain of intimin (Int188) from E. coli O157:H7 at 2.8 Å resolution, together with a mutant (IntN916Y) at 2.6 Å. We also built the structural model of EHEC intimin-Tir complex and analyzed the key binding residues. It suggested that the binding pattern of intimin and Tir between EHEC and Enteropathogenic E. coli (EPEC) adopt a similar mode and they can complement with each other. Detailed structural comparison indicates that there are four major points of structural variations between EHEC and EPEC intimins: one in Domain I (Ig-like domain), the other three located in Domain II (C-type lectin-like domain). These variations result in different binding affinities. These findings provide structural insight into the binding pattern of intimin to Tir and the molecular mechanism of EHEC O157: H7