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Hesperetin has been known to exert several activities such as anti-oxidant, antitumor and anti-inflammatory. To find hesperetin derivatives showing better activity, sixteen novel hesperetin derivatives were designed and synthesized. The new obtained compounds were investigated for their anti-inflammatory activity by inhibiting interleukin-1β (IL-1β), interleukin-6 (IL-6) and production of nitric oxide (NO) in mouse RAW264.7 macrophages, and the structure-activity relationship of them was discussed. Among them, the compound 1l, 2c demonstrated more effective inhibitory activity of IL-1β and IL-6, meanwhile, the compound 1l showed the best inhibition of NO production. The results of NO inhibition study were basically accord with the molecular docking results of inducible nitric oxide synthase (iNOS). Furthermore, the expression of LPS-induced iNOS and components of NF-κB signaling pathway were reduced by compound 1l. Our results suggest that the inhibitory effect of compound 1l on LPS-stimulated inflammatory mediator production in RAW 264.7 cells is associated with the suppression of NF-κB signaling pathway and inhibition of iNOS protein and iNOS activity. From in vivo study, it was also observed that compound 1l had hepato-protective and anti-inflammatory effects in CCl4-induced acute liver injury mouse models.

ABSTRAT Alcoholic liver disease (ALD) and its complication continued to be a major health problem throughout the world. Increasing evidence suggests that microRNA (miRNA) that regulate apoptosis, inflammation and lipid metabolism are affected by alcohol in ALD. MiR-200a has emerged as a major regulator in several liver diseases, but its role in ALD has not been elucidated. The aim of this study is to figure out the biological function of miR-200a in ALD and to explore its underlying mechanism. The expression pattern of miR-200a were analyzed in vitro and in vivo, we showed that miR-200a was up-regulated in ALD in AML-12 and primary hepatocyte. We then examined it's effect on cell apoptosis and identified zinc finger E-box binding homeobox 2 (ZEB2; also known as SIP1) as a direct target gene of miR-200a. Furthermore, reintroduction of ZEB2 could reverse the pro-apoptosis of miR-200a on AML-12. Taken together, our study demonstrated that miR-200a regulates the apoptosis of hepatocyte in ALD by directly target ZEB2, both of which could serve as new therapeutic targets for ALD.

A flavonoid hesperetin is reported to have a variety of biological activities, including anticancer, antiviral, antioxidant, neuroprotective and anti-inflammatory properties. Thirty-one novel hesperetin derivatives were designed, synthesized and evaluated for anti-inflammatory activity using RAW264.7 cells and CCl4-induced acute liver injury model. Among these compounds, 5b displayed the excellent anti-inflammatory activity on decreasing NO, IL-6 and TNF-α both in vitro and vivo. In addition, 5b could also reduce the release of NO, IL-6 and TNF-α production by LPS stimulated RAW 264.7 cell through MAPK and NF-κB signaling pathway in a concentration dependent manner. From in vivo study, it was also observed that 5b attenuated liver histopathologic changes in mouse models.

In this study we designed and synthesized a series of new hesperetin derivatives on the basis of the structural characteristics of acetylcholinesterase (AChE) dual-site inhibitors. The activity of the novel derivatives was also evaluated. Results showed that the synthesized hesperetin derivatives displayed stronger inhibitory activity against AChE and higher selectivity than butyrylcholine esterase (BuChE) (selectivity index values from 68 to 305). The Lineweaver-Burk plot and molecular docking study showed that these compounds targeted both the peripheral anionic site (PAS) and catalytic active site (CAS) of AChE. The derivatives also showed a potent self-induced β-amyloid (Aβ) aggregation inhibition and a peroxyl radical absorbance activity. Moreover, compound 4f significantly protected PC12 neurons against H2O2-induced cell death at low concentrations. Cytotoxicity assay showed that the low concentration of the derivatives does not affect the viability of the SH-SY5Y neurons. Thus, these hesperetin derivatives are potential multifunctional agents for further development for the treatment of Alzheimer’s disease.

The objective of the article is to construct a model to help Chinese government with water policymaking. This paper will take the policy of water price ladder model as an example,respectively pricing for municipal water and industrial water. The strategy of waters price ladder can promote the conservation of water resources.

Schizophrenia is a complex mental disorder with high degree of genetic influence in its etiology. Several recent studies revealed that copy number variations (CNVs) of genomic DNA contributed significantly to the genetic architecture of sporadic schizophrenia. This study aimed to investigate whether CNVs also contribute to the familial forms of schizophrenia. Using array-based comparative genomic hybridization technology, we searched for pathogenic CNV associated with schizophrenia in a sample of 60 index cases from multiplex schizophrenia families. We detected three inherited CNVs that were associated with schizophrenia in three families, including a microdeletion of ~ 4.4 Mb at chromosome 6q12–q13, a microduplication of ~ 1 Mb at chromosome 18q12.3, and an interstitial duplication of ~ 5 Mb at chromosome 15q11.2–q13.1. Our data indicate that CNVs contribute to the genetic underpinnings of the familial forms of schizophrenia as well as of the sporadic form. As 15q11–13 duplication is a well-known recurrent CNV associated with autism in the literature, the detection of the 15q11.2–q13.1 duplication in our schizophrenia patients provides additional support to other studies reporting that schizophrenia is part of the clinical spectrum of 15q11–q13 duplication syndrome.

Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, has been demonstrated to possess a strong antiangiogenic activity. However, the molecular mechanisms underlying this effect remain unclear. Endothelial cell (EC) migration is an essential component of angiogenesis, and the p38 mitogen-activated protein kinase (MAPK) signaling pathway plays a key role in the regulation of migration induced by vascular endothelial growth factor (VEGF). The aim of the present study was to investigate the effects of DHA on EC migration and the p38 MAPK signaling pathway. Human umbilical vein ECs (HUVECs) were treated with DHA and VEGF-induced migration was analyzed. The activation of p38 MAPK was detected by western blot analysis, and the migration assays were performed with a p38-specific inhibitor, SB203850. It was revealed that 20 μM DHA significantly reduced EC migration in the transwell migration assay, wound healing assay and electrical cell-substrate impedance sensing real-time analysis. However, DHA did not affect p38 MAPK phosphorylation or expression. In the absence or presence of SB203850, DHA induced a similar proportional reduction of EC migration in the three migration assays. Therefore, the present study demonstrated that DHA inhibits VEGF-induced EC migration via a p38 MAPK-independent pathway.

Plastics have become an integral part of our contemporary life because of many desirable properties including durability and resistance to degradation. However, these nondegradable, petrochemicals-derived plastics accumulate in the environment at a rate of 25 million tons per year. Recently there is an interest in the development of a class of microbially produced bioplastics, e.g., polyhydroxyalkanoates (PHAs) which retain the desired physical and chemical properties of conventional synthetic plastics. Broader usage of biodegradable plastics in packaging and disposable products as a solution to the environmental problem would heavily depend on further reduction of costs and the discovery of novel biodegradable plastics with improved properties. In this paper, the microbial production of PHAs by activated sludge utilizing food industrial wastes is reported. The melting points of the products as well as the co-polymer composition of the products investigated by GC and NMR were compared. By use of activated sludge to convert the carbon source into PHAs not only environment-friendly bioplastics are produce, but also part of the problem of the disposal of municipal activated sludge is solved. The selection of food industrial waste as carbon resource can also further reduce the cost of production of PHAs.

To study the influence of cervical settling method on marginal accuracy of wax patters.24 wax patterns were made on the standard cast specimens and round capsules of which twelve patters were made with the method of cervical settling (experiment group), twelve patters were made with the method of wax dripping (control group). Marginal accuracy of patterns were measured before sublation, sublation half an hour and twenty-four hours.The results revealed that marginal accuracy had significant difference between the cervical settling methods and wax dripping methods (P0.05). There was significant difference between the cervical settling methods measured after half an hour and twenty-four hours (P0.01). There was also significant difference between the wax dripping methods measured after half an hour and twenty-four hours (P0.01).Wax patterns with the method of cervical settling can improve marginal accuracy of patterns. The marginal accuracy of wax patters are influenced by the existing time.

The purpose of this study was to evaluate the effect of degradation of human root dentin collagen treated with collagenase after demineralization.The root dentin samples were demineralized by incubating with PH5.0 lactate acid at 37 degrees C. The incubation solutions were taken on days 1, 7, 14, 21 and 28, and centrifuged 10,000r/min at 4 degrees C. The supernature solutions were analyzed for Ca(2+) and hydroxyproline. The demineralized root samples were incubated with PH7.4 collagenase solution for 7 days at 37 degrees C. The incubation solutions were centrifuged 10,000r/min at 4 degrees C and analyzed for hydroxyproline.The release of Ca(2+) increased and had significant differences at all observation periods within 28 days (P0.05). There were no significant differences of the amount of degradable collagen during the nonenzymatic procedure (P0.05). The amount of collagenase-degradable collagen was proportional to the calcium released until a plateau value at a calcium loss of about 80.01 micromol/cm(2) was reached.The degradability of collagenase is in close association with calcium released. The retention of mineral is of relevance for lesion arrestment or remineralization of early root caries.

The purpose of this study was to observe the effect on marginal seating of the castings with and without ring investments.Standarded as-cast specimens and round capsules simulated post tooth crowns were made. 12 wax pattern were prepared on the as-cast specimens. The 12 specimens were divided into two groups with 6 wax pattern in each group. Two different investing methods with the same investing material were tested. The marginal seating of the castings was measured under travelling microscope.The marginal seating of the casting without ring investment had significant difference compared with the castings with ring investment (P0.05).Casting without ring can improve the marginal seating of the castings.

Broader usage of biodegradable plastics in packaging and disposable products as a solution to environmental problems would heavily depend on further reduction of costs and the discovery of novel biodegradable plastics with improved properties. As the first step in our pursuit of eventual usage of industrial food wastewater as nutrients for microorganisms to synthesise environmental-friendly bioplastics, we investigated the usage of soya wastes from a soya milk dairy, and malt wastes from a beer brewery plant as the carbon sources for the production of polyhydroxyalkanoates (PHA) by selected strain of microorganism. Bench experiments showed that Alcaligenes latus DSM 1124 used the nutrients from malt and soya wastes to biosynthesise PHAs. The final dried cell mass and specific polymer production of A. latus DSM 1124 were 32g/L and 70% polymer/cells (g/g), 18.42 g/L and 32.57% polymer/cell (g/g), and 28 g/L and 36% polymer/cells (g/g), from malt waste, soya waste, and from sucrose, respectively. These results suggest that many types of food wastes might be used as the carbon source for the production of PHA.

Background Yuli Veterans Hospital (YVH) has been the largest mental hospital for the patients with chronic and severe mental illness in Taiwan for the past 50 years. While this hospital used to be a symbol of hopelessness among patients and their families and an unspoken shame among Taiwan psychiatry and mental health circles it now represents an example of how an old, custodial hospital can be transformed into a very different institution. In this case study we will describe the features of this transformation, which, over the past 20 years, has aimed to help extended stay inpatients with severe mental illness to integrate into the local community of Yuli even though it is not their original home. Methods Using historical documents and oral narratives from Yuli inhabitants, workers and patients of YVH, we will offer a case study of the Yuli model. Results There are four main components of the Yuli model: holistic medical support, vocational rehabilitation, case management, and the residential program. The four components help patients recover two essential features of their lives: vocational life and ordinary daily routines. As the process of recovery evolves, patients gradually regain inner stability, dignity, self-confidence, and a sense of control. The four components are critical to rebuild the structure and order of life of the patients and are indispensable and interdependent parts of one service package. They operate simultaneously to benefit the patients to the greatest degree possible. Discussion There are many challenges to the further development and financial viability of the model of services developed at YVH. There are also important questions concerning the replicability of the Yuli model in other sociocultural and service system contexts. Conclusion This case study reveals the possibility of transforming a custodial mental hospital into a hospital providing high quality care. Hospital and community are not in opposition. They are part of a continuum of care for the patients. We reinterpret and redefine the boundary and function of hospital and community, and thereby create a new service model, the Yuli Model, to help patients to reintegrate into the community. The Yuli model, which particularly focuses on the needs of people with long-standing illness and prolonged hospital stay, illustrates one approach to linking hospital and community in a creative and constructive manner.