Chitinase-3 like-protein-1, matrix metalloproteinase -9 and positive intracranial arterial remodelling

IntroductionPositive intracranial arterial remodelling is a dilated lesion of the large intracranial vessels; however, its pathogenesis is currently unknown. Some studies have identified chitinase-3 like-protein-1 (YKL-40) and matrix metalloproteinase (MMP)-9 as circulating inflammatory factors involved in positive vascular remodelling. Herein, we aimed to investigate the relationship between changes in serum YKL-40 and MMP-9 levels and positive intracranial arterial remodelling in patients with cerebral small vessel disease (CSVD).MethodsA total of 110 patients with CSVD were selected. Patients with brain arterial remodelling (BAR) scores >1 times the standard deviation were defined as the positive intracranial artery remodelling group (n = 21 cases), and those with BAR scores ≤1 times the standard deviation were defined as the non-positive intracranial artery remodelling group (n = 89 cases). Serum YKL-40 and MMP-9 levels were measured using an enzyme-linked immunosorbent assay kit. Factors influencing positive intracranial artery remodelling using binary logistic regression analysis and predictive value of YKL-40 and MMP-9 for positive intracranial arterial remodelling in patients with CSVD were assessed by a subject receiver operating characteristic curve.ResultsStatistically significant differences in serum YKL-40 and MMP-9 levels were observed between the positive and non-positive remodelling groups (p < 0.05). The integrated indicator (OR = 9.410, 95% CI: 3.156 ~ 28.054, P<0.01) of YKL-40 and MMP-9 levels were independent risk factors for positive intracranial arterial remodelling. The integrated indicator (OR = 3.763, 95% CI: 1.884 ~ 7.517, p < 0.01) of YKL-40 and MMP-9 were independent risk factors for positive arterial remodelling in posterior circulation, but were not significantly associated with positive arterial remodelling in anterior circulation (p > 0.05). The area under the curve for YKL-40 and MMP-9 diagnostic positive remodelling was 0.778 (95% CI: 0.692–0.865, p < 0.01) and 0.736 (95% CI: 0.636–0.837, p < 0.01), respectively.DiscussionElevated serum YKL-40 and MMP-9 levels are independent risk factors for positive intracranial arterial remodelling in patients with CSVD and may predict the presence of positive intracranial arterial remodelling, providing new ideas for the mechanism of its occurrence and development and the direction of treatment

Glycyrrhizic acid-phospholipid complex: preparation process optimization and therapeutic and pharmacokinetic evaluation in rats

The purpose of the present study was to prepare glycyrrhizic acid-phospholipid complex (GL-PLC) as to improve the oral bioavailability of glycyrrhizic acid (GL), enhance the drug efficacy and reduce the side effects. The uniform experimental design approach was utilized for the process optimization in order to obtain the satisfactory complex. The results of comparison between GL-PLC and free GL indicated that the anti-inflammatory activity of the phospholipid complex was significantly higher than that of free GL at the same dose. The results of pharmacokinetic study displayed that the plasma concentration of glycyrrhetic acid, the metabolite of GL in vivo, increased after oral administration of GL-PLC. The Cmax of GL-PLC was 2.14 times higher than that of free glycyrrhizic acid, while the AUC of GL-PLC was 1.74 times higher than that of free GL. The results proved that GL-PLC improved the lipophilic property of GL, increased the bioavailability and anti-inflammatory activity.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Regulation of Prostate Development and Benign Prostatic Hyperplasia by Autocrine Cholinergic Signaling via Maintaining the Epithelial Progenitor Cells in Proliferating Status

SummaryRegulation of prostate epithelial progenitor cells is important in prostate development and prostate diseases. Our previous study demonstrated a function of autocrine cholinergic signaling (ACS) in promoting prostate cancer growth and castration resistance. However, whether or not such ACS also plays a role in prostate development is unknown. Here, we report that ACS promoted the proliferation and inhibited the differentiation of prostate epithelial progenitor cells in organotypic cultures. These results were confirmed by ex vivo lineage tracing assays and in vivo renal capsule recombination assays. Moreover, we found that M3 cholinergic receptor (CHRM3) was upregulated in a large subset of benign prostatic hyperplasia (BPH) tissues compared with normal tissues. Activation of CHRM3 also promoted the proliferation of BPH cells. Together, our findings identify a role of ACS in maintaining prostate epithelial progenitor cells in the proliferating state, and blockade of ACS may have clinical implications for the management of BPH

A novel fusion protein consisting of anti-ANGPTL3 antibody and interleukin-22 ameliorates diabetic nephropathy in mice

IntroductionThe pathogenic mechanisms of diabetic nephropathy (DN) include podocyte injury, inflammatory responses and metabolic disorders. Although the antagonism of Angiopoietin-like protein 3 (ANGPTL3) can alleviate proteinuria symptoms by inhibiting the activation of integrin αvβ3 on the surface of podocytes, it can not impede other pathological processes, such as inflammatory responses and metabolic dysfunction of glucolipid. Interleukin-22 (IL-22) is considered to be a pivotal molecule involved in suppressing inflammatory responses, initiating regenerative repair, and regulating glucolipid metabolism.MethodsGenes encoding the mIL22IgG2aFc and two chains of anti-ANGPTL3 antibody and bifunctional protein were synthesized. Then, the DN mice were treated with intraperitoneal injection of normal saline, anti-ANGPTL3 (20 mg/kg), mIL22Fc (12 mg/kg) or anti-ANGPTL3 /IL22 (25.3 mg/kg) and irrigation of positive drug losartan (20mg/kg/d) twice a week for 8 weeks.ResultsIn this research, a novel bifunctional fusion protein (anti-ANGPTL3/IL22) formed by the fusion of IL-22 with the C-terminus of anti-ANGPTL3 antibody exhibited favorable stability and maintained the biological activity of anti-ANGPTL3 and IL-22, respectively. The fusion protein showed a more pronounced attenuation of proteinuria and improved dysfunction of glucolipid metabolism compared with mIL22Fc or anti-ANGPTL3. Our results also indicated that anti-ANGPTL3/IL22 intervention significantly alleviated renal fibrosis via inhibiting the expression of the inflammatory response-related protein nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) p65 and NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome. Moreover, transcriptome analysis revealed the downregulation of signaling pathways associated with injury and dysfunction of the renal parenchymal cell indicating the possible protective mechanisms of anti-ANGPTL3/IL22 in DN.ConclusionCollectively, anti-ANGPTL3/IL22 bifunctional fusion protein can be a promising novel therapeutic strategy for DN by reducing podocyte injury, ameliorating inflammatory response, and enhancing renal tissue recovery

A Type 2C Protein Phosphatase FgPtc3 Is Involved in Cell Wall Integrity, Lipid Metabolism, and Virulence in Fusarium graminearum

Type 2C protein phosphatases (PP2Cs) play important roles in regulating many biological processes in eukaryotes. Currently, little is known about functions of PP2Cs in filamentous fungi. The causal agent of wheat head blight, Fusarium graminearum, contains seven putative PP2C genes, FgPTC1, -3, -5, -5R, -6, -7 and -7R. In order to investigate roles of these PP2Cs, we constructed deletion mutants for all seven PP2C genes in this study. The FgPTC3 deletion mutant (ΔFgPtc3-8) exhibited reduced aerial hyphae formation and deoxynivalenol (DON) production, but increased production of conidia. The mutant showed increased resistance to osmotic stress and cell wall-damaging agents on potato dextrose agar plates. Pathogencity assays showed that ΔFgPtc3-8 is unable to infect flowering wheat head. All of the defects were restored when ΔFgPtc3-8 was complemented with the wild-type FgPTC3 gene. Additionally, the FgPTC3 partially rescued growth defect of a yeast PTC1 deletion mutant under various stress conditions. Ultrastructural and histochemical analyses showed that conidia of ΔFgPtc3-8 contained an unusually high number of large lipid droplets. Furthermore, the mutant accumulated a higher basal level of glycerol than the wild-type progenitor. Quantitative real-time PCR assays showed that basal expression of FgOS2, FgSLT2 and FgMKK1 in the mutant was significantly higher than that in the wild-type strain. Serial analysis of gene expression in ΔFgPtc3-8 revealed that FgPTC3 is associated with various metabolic pathways. In contrast to the FgPTC3 mutant, the deletion mutants of FgPTC1, FgPTC5, FgPTC5R, FgPTC6, FgPTC7 or FgPTC7R did not show aberrant phenotypic features when grown on PDA medium or inoculated on wheat head. These results indicate FgPtc3 is the key PP2C that plays a critical role in a variety of cellular and biological functions, including cell wall integrity, lipid and secondary metabolisms, and virulence in F. graminearum

The Impact of Internal Courtyard Configuration on Thermal Performance of Long Strip Houses

A courtyard is an essential space for natural lighting and natural convective ventilation of residential buildings in hot-humid climates. This study focuses on the internal courtyard configuration on the thermal performance of long strip houses (LSH) in the hot-climate area of Hainan Island, China. The aim is to identify the best design parameters for the courtyard to improve thermal comfort in modern LSH design. Appropriate strategies, including Mahoney table, field investigation, and CFD simulation, are used to determine thermal performance. As a result, the design guidelines of the courtyard are proposed to optimize the thermal comfort towards energy saving. The study reveals the spatial characteristics and climate regulation of internal courtyards in traditional LSH. In addition, the simulation results show that the enclosure with a shaded cover and a high ratio of H/D is conducive to thermal environment and ventilation, and the section of contracted shape from bottom to top is a preferred option in the internal courtyard configuration. This study should, therefore, be of value in designing practical projects with an interior courtyard for architects

Influence of space properties of enclosed patio on thermal performance in hot-humid areas of China

Patio plays an important role in climate adaptation and microclimate adjustment of buildings. This study aims to explore enclosed patio design guidelines, which are essential for both architectural design methodology and practical projects for providing better thermally comfortable indoor and outdoor spaces. A combined qualitative and quantitative methodological approach was used to clarify how the passive design strategies of the enclosed patio affect the thermal environment of houses around the patio. The findings reveal the spacial characteristics and thermal adjustment of enclosed patios. The results of simulation indicate that appropriate design parameters of enclosed patio can achieve a better indoor and outdoor thermal comfort environment for its users, which includes similar dimension in width and depth, increased number of windows in a high ratio of width to depth, semi-open auxiliary space, 3-4 floor height, upper-lower double windows of four-sided enclosed patio and south opening direction of three-sided enclosed patio

Research on Optimization Model of Logistics Transportation Truck Path considering Environmental Impact: Experimental Data from Xiqing District, Tianjin

In recent years, the prohibition of trucks which could cause environmental pollution on urban roads has become widespread in China. However, some truck restriction policies might lead to a reduction in logistics transportation efficiency. With the help of big data, technology companies have developed many truck applications, such as HCB, truck home, and truck help, to provide the drivers available traffic information. In this context, this paper put forward a truck path optimization model considering environmental impact (TPOM-EI), which is solved by a heuristic algorithm—ant colony optimization (ACO) algorithm. Most previous studies focused on unilateral benefits rather than overall benefits; this paper aims to propose a path optimization model based on real-time minimization of social and transportation costs. Finally, data of Xiqing Economic and Technological Development Zone in Tianjin city (XQ-EDZ) have been used to demonstrate the applicability of the proposed algorithm. The results show that logistics truck path has a huge impact on social costs, and real-time activities in various areas will also change the path of a truck. This research will also help logistics truck drivers to choose the best route in real time

The Impact of Consumer Participation Certification on the Trust of Eco-Agricultural Products Based on the Mediating Effects of Information and Identity

With the increasing distrust of food safety, both third-party certification systems (TPC) and participatory guarantee systems (PGS) play a vital role in restoring consumer trust. Although the fact that previous research has focused on consumer trust and the factors that impact it in TPC products, little emphasis has been made on how consumer participation in certification affects trust. The goal of the study was to explore how consumer participation certification affects trust in eco-agricultural products under PGS. We constructed a theoretical framework of consumer trust in eco-agricultural products under PGS, based on consumer trust theory, and clarified the relationship between consumer participation certification, information quality, social identity, and consumer trust. After obtaining 238 valid questionnaires on consumers from 12 PGS organizations nationwide, a structural equation model (SEM) was conducted. The conclusions are as follows: (1) Consumer participation has a positive impact on consumer trust, and the direct effect is not significant, but the indirect effect is significant; (2) Information quality and social identity have been identified to play full intermediary roles in the relationship between consumer participation and trust. We suggest relevant research implications and recommendations for future research on consumer trust in PGS based on the findings