Alterations in leptin expression contributes to the progression of various diseases, including cancers. This meta-analysis investigated the clinical significance of leptin levels in osteoarthritis ...(OA) patients, with the goal of building a leptin-based diagnostic criterion for OA.
Multiple scientific databases in English and Chinese languages, such as the Cochrane Library Database, CINAHL, Chinese Biomedical (CBM), EMBASE, PubMed, and Web of Science, were exhaustively searched, without any language restrictions, to identify high-quality studies relevant to leptin and OA. Version 12.0 STATA software was used for data analysis. We used odds ratios (OR) and 95% confidence intervals (CI) to test the correlation between serum leptin levels and OA progression.
A total of 11 clinical studies were finally selected for their high quality and relevance to the topic in this meta-analysis. The 11 case-control studies contained a combined total of 3,625 subjects. The meta-analysis results showed that leptin expression was significantly increased in OA patients, compared with the controls (SMD = 0.87, 95%CI: 0.72-1.02, P < 0.001), and there was also a strong association between leptin expression levels and gender (SMD = 8.55, 95%CI: 4.74-12.35, P < 0.001). In ethnicity-stratified subgroup analysis, all the study populations, irrespective of ethnicity, showed remarkably high leptin expression levels in females and in OA patients (all P < 0.05), compared to their respective counterparts.
The present study revealed that increased leptin expression levels are associated with disease severity in OA patients, especially among the female OA patients. Based on our results, we propose that leptin level may be a useful biomarker for the assessment of the clinical status in OA patients.
The modulation of gene expression via DNA methylation modifications is relevant to the pathogenesis of periodontitis. This study aimed at identifying novel biomarkers in gingival tissues from ...periodontitis by integrally analyzing methylation profiles and gene expression data. Differential gene expressions (DGEs) of dataset GSE106090 were obtained from the Gene Expression Omnibus (GEO) database for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. DNA methylation DGEs (DM-DGEs) were analyzed from dataset GSE173082. After integrating these two datasets, expressions of common genes were validated in gingival tissues from healthy controls and periodontitis patients by real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting. GO analysis of 748 upregulated and 847 downregulated DEGs from the GSE106090 dataset revealed that immune response-regulating signaling pathway, cell-cell junction and signaling receptor activator activity as the top enriched biological process (BP), cellular component (CC) and molecular function (MF), respectively. DEGs were mainly enriched in cytokine-cytokine receptor interaction, Ras signaling pathway, and chemokine signaling pathway. There was one up-regulated mRNA with hypo-methylated gene ADAM28 (a disintegrin and metalloproteinase 28) and one down-regulated mRNA with hyper-methylated gene ADAMTSL3 (a disintegrin-like and metalloprotease domain with thrombospondin type I motifs-like-3) after integrating GSE106090 and GSE173082 datasets. Increased ADAM28 expression was validated in gingival tissues from periodontitis patients as compared to the healthy controls with decreased ADAMTSL3 expression, which were correlated with disease stage. ADAM28 and ADAMTSL3 may act as novel biomarkers in gingival tissues from periodontitis by a comprehensive analysis of bioinformatics methods and executed validation.
Aim: Aquaporins (AQPs) are the water-channels that play important roles in brain water homeostasis and in cerebral edema induced by brain injury. In this study we investigated the relationship ...between AQPs and a neuroprotective agent curcumin that was effective in the treatment of brain edema in mice with intracerebral hemorrhage (ICH). Methods: ICH was induced in mice by autologous blood infusion. The mice immediately received curcumin (75, 150, and 300 mg/kg, ip). The Rotarod test scores, brain water content and brain expression of AQPs were measured post ICH. Cultured primary mouse astrocytes were used for in vitro experiments. The expression of AQP1, AQP4 and AQP9 and NF-KB p65 were detected using Western blotting or immunochemistry staining. Results: Curcumin administration dose-dependently reduced the cerebral edema at d 3 post ICH, and significantly attenuated the neurological deficits at d 5 post ICH. Furthermore, curcumin dose-dependently decreased the gene and protein expression of AQP4 and AQPg, but not AQP1 post ICH. Treatment of the cultured astrocytes with Fe2+ (10-100μmol/L) dose-dependently increased the expression and nuclear translocation of NF-kB p65 and the expression of AQP4 and AQP9, which were partly blocked by co-treatment with curcumin (20 pmol/L) orthe NF-kB inhibitor PDTC (10 pmol/L). Conclusion: Curcumin effectively attenuates brain edema in mice with ICH through inhibition of the NF-kB pathway and subsequently the expression of AQP4 and AQP9. Curcumin may serve as a potential therapeutic agent for ICH.
High-entropy alloys with high strength and acceptable ductility at both room and elevated temperatures for high-temperature structural applications are desired. In this paper, CrMnFeCoNi alloy with ...outstanding ductility but low strength was selected as baseline alloy to study the formation of hard phase to strengthen this ductile alloy by adding Al into it. The results indicate that there is a phase structure transition from fcc to bcc when adding enough Al into CrMnFeCoNi. The yield strength and hardness increase with the content of Al increasing, due to the formation of hard bcc phase in the ductile CrMnFeCoNi alloy. The CrMnFeCoNiAl alloy with a bcc structure shows a high yield strength and adequate ductility at elevated temperatures. At 400 and 500 °C, the yield strength and ductility of CrMnFeCoNiAl alloy are 975.59 MPa and 6.39% and 989.48 MPa and 9.15%, respectively. An example of tailoring the strength and ductility of high-entropy alloy is demonstrated in this paper.
Cryptocaryon irritans, a marine fish ectoparasite, causes mass economic loss in the mariculture and ornamental fish industries. It is important to find effective alternatives that may be both ...affordable and environmentally acceptable to control the damage of C. irritans. In this study, honokiol from Magnolia officinalis was screened from 36 phytochemical compounds for its significant antiparasitic activity against C. irritans theronts. Honokiol at a concentration of 1.00 μg/mL resulted in 100% mortality of C. irritans theronts within 30 min of exposure and >88.6% inhibition of tomont and protomont transformations post 8-h exposure to 1.00 and 4.00 μg/mL, respectively. Moreover, after exposure to 0.80, 1.00, and 4.00 μg/mL of honokiol solution for 30 min, 8 h, and 8 h, abnormal morphologies of theronts, tomonts, and trophonts were observed, respectively. After consecutively fed a diet containing 400 mg/kg of honokiol for 7 d, pompano (Trachinotus ovatus) were exposed to C. irritans theronts and the results showed that the number of C. irritans trophonts on the pompanos' gills was significantly lower than that in the control group 3 days later, while a similar efficacy was observed at doses above 100 mg/kg 8 days later. In addition, a dose of 200 mg/kg honokiol significantly reduced the chemotaxis of C. irritans theronts to the sera; meanwhile, the chemotaxis of C. irritans theronts to dorsal trunk muscle solutions was significantly reduced at doses above 100 mg/kg. Compared to the control group, a dose of 400 mg/kg honokiol increased the survival rate of the infected pompano by 65 ± 5% (mean ± SE). The results of hemolysis assay showed that the EC1 of honokiol to pompano erythrocytes was 6.36 μg/mL, 6.36 times the concentration that allowed honokiol to completely stop the movement of 100% C. irritans theronts in 30 min. Therefore, honokiol has the potential to be a safe and effective candidate, and could also serve as a leading compound in the development of a commercial drug to control C. irritans in mariculture.
•Cryptocaryon irritans causes mass economic loss in the mariculture and ornamental fish industries.•Honokiol from Magnolia officinalis has significant antiparasitic efficacy against Cryptocaryon irritans in pompano.•Honokiol can significantly reduce the chemotaxis of C. irritans theronts to the serums and back muscle solution.•Honokiol at dose for controlling C. irritans is safe for pompano.
Cryptocaryon irritans, a common parasite in tropical and subtropical marine teleost fish, has caused serious harm to the marine aquaculture industry. Honokiol was proven to induce C. irritans tomont ...cytoplasm shrinkage and death in our previous study, but the mechanism by which it works remains unknown. In this study, the changes of apoptotic morphology and apoptotic ratio were detected by microscopic observation and AnnexinV-FITC/PI staining. The effects of honokiol on intracellular calcium (Ca.sup.2+.sub.i) concentration, mitochondrial membrane potential (DELAΨm), reactive oxygen species (ROS), quantity of DNA fragmentations (QDF) and caspase activities were detected by Fluo-3 staining, JC-1 staining, DCFH-DA staining, Tunel method and caspase activity assay kit. The effects of honokiol on mRNA expression levels of 61 apoptosis-related genes in tomonts of C. irritans were detected by real-time PCR. The results of the study on the effects of honokiol concentration on C. irritans tomont apoptosis-like death showed that the highest levels of prophase apoptosis-like death rate (PADR), Ca.sup.2+.sub.i concentration, ROS, the activities of caspase-3/9 and the lowest necrosis ratio (NER) were obtained at a concentration of 1 mug/ml, which was considered the most suitable for inducing C. irritans tomont apoptosis-like death. When C. irritans tomonts were treated with 1 mug/ml honokiol, the Ca.sup.2+.sub.i concentration began to increase significantly at 1 h. Following this, the ROS, QDF and activities of caspase-3/9 began to increase significantly, and the DELAΨm began to decrease significantly at 2 h; the highest PADR was obtained at 4 h. The mRNA expression of 14 genes was significantly upregulated during honokiol treatment. Of these genes, itpr2, capn1, mc, actg1, actb, parp2, traf2 and fos were enriched in the pathway related to apoptosis induced by endoplasmic reticulum (ER) stress. This article shows that honokiol can induce C. irritans tomont apoptosis-like death. These results suggest that honokiol may disrupt Ca.sup.2+.sub.i homeostasis in ER and then induce C. irritans tomont apoptosis-like death by caspase cascade or mitochondrial pathway, which might represent a novel therapeutic intervention for C. irritans infection.
Cryptocaryon irritans is a fatal parasite for marine teleosts and causes severe economic loss for aquaculture. Galvanized materials have shown efficacy in controlling this parasite infestation ...through the release of zinc ions to induce oxidative stress. In this study, the resistance mechanism in C. irritans against oxidative stress induced by zinc ions was investigated. Untargeted metabolomics analysis was used to determine metabolic regulation in C. irritans in response to zinc ion treatment by the immersion of protomonts in ZnSO.sub.4 solution at a sublethal dose (20 mumol). Eight differential metabolites were selected to assess the efficacy of defense against zinc ion stimulation in protomonts of C. irritans. Furthermore, the mRNA relative levels of glutathione metabolism-associated enzymes were measured in protomonts following treatment with ZnSO.sub.4 solution at sublethal dose. The results showed that zinc ion exposure disrupted amino acid metabolism, carbohydrate metabolism, lipid metabolism, and nucleotide metabolism in C. irritans. Four antioxidants, namely ascorbate, S-hexyl-glutathione, syringic acid, and ubiquinone-1, were significantly increased in the Zn group (P < 0.01), while the glutathione metabolism pathway was enhanced. The encystment rate of C. irritans was significantly higher in the ascorbate and methionine treatment (P < 0.05) groups. Additionally, at 24 h post-zinc ion exposure, the relative mRNA level of glutathione reductase (GR) was increased significantly (P < 0.01). On the contrary, the relative mRNA levels of glutathione S-transferase (GT) and phospholipid-hydroperoxide glutathione peroxidase (GPx) were significantly decreased (P < 0.05), thus indicating that the generation of reduced glutathione was enhanced. These results revealed that glutathione metabolism in C. irritans contributes to oxidative stress resistance from zinc ions, and could be a potential drug target for controlling C. irritans infection.
The protozoan Cryptocaryon irritans is one of the most important ectoparasites of marine fish, causing ‘white spot disease’ and mass mortality in aquaculture. To accurately predict disease outbreaks ...and develop prevention strategies, improved detection methods are required that are sensitive, convenient and rapid. In this study, a pair of specific primers based on the C. irritans 18S rRNA gene was developed and used in a real‐time PCR (qPCR) assay. This assay was able to detect five theronts in 1 L of natural seawater. Furthermore, a linear model was established to analyse the log of Ct value and parasite abundance in seawater (y = –2.9623x + 24.2930), and the coefficient of determination (R2) value was 0.979. A lysis buffer was optimized for theront DNA extraction and used for storage sample. This method was superior to the commercial water DNA kit, and there was no significant degradation of DNA at room temperature for 24–96 hr. A dilution method was developed to manage qPCR inhibitors and used to investigate natural seawater samples in a net cage farm with diseased fish, and the findings were consistent with the actual situation. This study provides a valuable tool for assisting in the early monitoring and control of cryptocaryoniasis in aquaculture.
A weak form quadrature element formulation is established for finite deformation consolidation problems of an elasto-plastic saturated soft clay. The total Lagrangian (TL) description scheme and the ...weak form description of Biot’s theory are adopted in the derivation of the formulation. The constitutive model of the soil skeleton is based on a multiplicative decomposition of the deformation gradient into elastic and plastic parts. The exponential flow relation between the velocity of pore fluid and hydraulic gradient is used to describe the continuity condition in Biot’s theory. Results of numerical examples are compared with those of ABAQUS and previous studies, and very good agreement is reached, demonstrating the reliability and efficiency of the present formulation. The effect of non-Darcian flow on consolidation in the finite strain range is discussed and it is shown that, with the increase of the non-Darcian model parameters, the rate of consolidation and the differential settlement decrease.
The weak form quadrature element method is a high-order algorithm which has been applied successfully to consolidation analysis of saturated and unsaturated soils. Its superiority over the ...conventional finite element method has been verified. However, in consolidation analysis, pore pressure oscillations will appear when small time increments are used due to the very small permeability and near-incompressibility of the pore water. This can produce almost zero values of main diagonal elements in the coefficient matrix. To overcome the pressure oscillations, we propose a coupled composite quadrature element in which different orders of integration are employed for the pore pressure and the displacement. Its performance is evaluated and compared with that of the standard element through 1D and 2D numerical tests. Our results show that pressure oscillations can be effectively alleviated and stability and accuracy can be significantly enhanced by using the proposed element.