Heparan sulfate differences in rheumatoid arthritis versus healthy sera

Heparan sulfate (HS) is a complex and highly variable polysaccharide, expressed ubiquitously on the cell surface as HS proteoglycans (HSPGs), and found in the extracellular matrix as free HS fragments. Its heterogeneity due to various acetylation and sulfation patterns endows a multitude of functions. In animal tissues, HS interacts with a wide range of proteins to mediate numerous biological activities; given its multiple roles in inflammation processes, characterization of HS in human serum has significant potential for elucidating disease mechanisms. Historically, investigation of HS was limited by its low concentration in human serum, together with the complexity of the serum matrix. In this study, we used a modified mass spectrometry method to examine HS disaccharide profiles in the serum of 50 women with rheumatoid arthritis (RA), and compared our results to 51 sera from healthy women. Using various purification methods and online LC–MS/MS, we discovered statistically significant differences in the sulfation and acetylation patterns between populations. Since early diagnosis of RA is considered important in decelerating the disease's progression, identification of specific biomolecule characterizations may provide crucial information towards developing new therapies for suppressing the disease in its early stages. This is the first report of potential glycosaminoglycan biomarkers for RA found in human sera, while acknowledging the obvious fact that a larger population set, and more stringent collection parameters, will need to be investigated in the future.The authors gratefully acknowledge the financial support provided by the National Institutes of Health (Grant GM 47356)

Disturbed eating tendencies, health-related behaviors, and depressive symptoms among university students in Korea

Summary: Background & aims: There were few studies to investigate the related factors of depression among Korean students. Therefore, this study examined disturbed eating tendencies, health-related behaviors, and depressive symptoms among university students in Korea. Methods: We conducted a cross-sectional survey on a total of 637 students (279 men and 358 women), and the Korean version of the Beck depression rating scale (K-BDI) was used to evaluate the students' depression status. Results: Of the 637 students, 419 (65.8%) had no depressive symptoms (normal: K-BDI<10), whereas 136 (21.4%: K-BDI 10–16), 69 (10.8%: K-BDI 17–29), and 13 (2.0%: K-BDI≥30) had mild, moderate, and severe depressive symptoms, respectively. Multivariable logistic regression showed that depressive symptoms (K-BDI≥10) were associated with female gender (odds ratio [OR] = 1.86, 95% confidence interval [CI] = 1.26 to 2.76; p = .002), high level of life stress (OR = 4.37, 95% CI = 2.23 to 8.55; p < .001), and disturbed eating behaviors (Korean version of Eating Attitude Test-26 ≥ 20; OR = 5.14, 95% CI = 2.52 to 10.5; p < .001). In contrast, depressive symptoms were inversely associated with a high body image satisfaction (OR = 0.37, 95% CI = 0.20 to 0.68; p = .001) and self-esteem (self-esteem score≥30) (OR = 0.29, 95% CI = 0.20 to 0.43; p < .001). Conclusions: This study confirmed that students with depressive symptoms tended to have disturbed eating behaviors, low body image satisfaction, low self-esteem, and high levels of stress. Keywords: Depression, Disturbed eating attitude, Health behavior, Depressive symptoms, Korean student

Differentiation of CC vs CXC Chemokine Dimers with GAG Octasaccharide Binding Partners: An Ion Mobility Mass Spectrometry Approach

Chemokines, 8 kDa proteins implicated in leukocyte migration via oligomerization, bind to glycosaminoglycans (GAGs) during the inflammation response as a means to regulate chemokine migration. Structural characterization of chemokines non-covalently bound to GAGs provides physiologically meaningful data in regard to routine inmmunosurveillance and disease response. In order to analyze the structures resulting from the GAG:chemokine interaction, we employed ion mobility mass spectrometry (IMMS) to analyze monocyte chemoattractant protein‑1 (MCP‑1), a CC chemokine, and interleukin‑8 (IL‑8), a CXC chemokine, along with their individual interactions with GAG heparin octasaccharides. We show that MCP‑1 and IL‑8 are physiologically present as a dimer, with MCP‑1 having two variants of its dimeric form and IL‑8 having only one. We also show that the MCP‑1 dimer adopts two conformations, one extended and one compact, when bound to a dodecasulfated heparin octasaccharide. Binding of MCP‑1 to heparin octasaccharide isomers of varying sulfation patterns results in similar arrival time distribution values, which suggests minimal distinguishing features among the resultant complexes. Additionally, tandem mass spectrometry (MS/MS) showed that the binding of MCP‑1 to a heparin octasaccharide has different dissociation patterns when compared with the corresponding IL‑8 bound dimer. Overall, IMMS and MS/MS were used to better define the structural tendencies and differences associated with CC and CXC dimers when associated with GAG octasaccharides

Inhibitory Effects of AF-343, a Mixture of Cassia tora L., Ulmus pumila L., and Taraxacum officinale, on Compound 48/80-Mediated Allergic Responses in RBL-2H3 Cells

The purpose of this study was to determine the antiallergic effects of AF-343, a mixture of natural plant extracts from Cassia tora L., Ulmus pumila L., and Taraxacum officinale, on rat basophilic leukemia (RBL-2H3) cells. The inhibitory effects on cell degranulation, proinflammatory cytokine secretion, and reactive oxygen species (ROS) production were studied in compound 48/80-treated RBL-2H3 cells. The bioactive compounds in AF-343 were also identified by HPLC&ndash;UV. AF-343 was found to effectively suppress compound 48/80-induced &beta;-hexosaminidase release, and interleukin (IL)-4 and tumor necrosis factor-&alpha; (TNF-&alpha;) production in RBL-2H3 cells. In addition, AF-343 exhibited DPPH free radical scavenging effects in vitro (half-maximal inhibitory concentration (IC50) = 105 &mu;g/mL) and potently inhibited compound 48/80-induced cellular ROS generation in a 2&prime;,7&prime;-dichlorofluorescein diacetate (DCFH-DA) assay. Specifically, treatment with AF-343 exerted stronger antioxidant effects in vitro and antiallergic effects in cells than treatment with three single natural plant extracts. Furthermore, AF-343 was observed to contain bioactive compounds, including catechin, aurantio-obtusin, and chicoric acid, which have been reported to elicit antiallergic responses. This study reveals that AF-343 attenuates allergic responses via suppression of &beta;-hexosaminidase release, IL-4 and TNF-&alpha; secretion, and ROS generation, perhaps through mechanisms related to catechin, aurantio-obtusin, and chicoric acid. The results indicate that AF-343 can be considered a treatment for various allergic diseases

Genetically Engineered Mouse Models for Liver Cancer

Liver cancer is the fourth leading cause of cancer-related death globally, accounting for approximately 800,000 deaths annually. Hepatocellular carcinoma (HCC) is the most common type of liver cancer, comprising approximately 80% of cases. Murine models of HCC, such as chemically-induced models, xenograft models, and genetically engineered mouse (GEM) models, are valuable tools to reproduce human HCC biopathology and biochemistry. These models can be used to identify potential biomarkers, evaluate potential novel therapeutic drugs in pre-clinical trials, and develop molecular target therapies. Considering molecular target therapies, a novel approach has been developed to create genetically engineered murine models for HCC, employing hydrodynamics-based transfection (HT). The HT method, coupled with the Sleeping Beauty transposon system or the CRISPR/Cas9 genome editing tool, has been used to rapidly and cost-effectively produce a variety of HCC models containing diverse oncogenes or inactivated tumor suppressor genes. The versatility of these models is expected to broaden our knowledge of the genetic mechanisms underlying human hepatocarcinogenesis, allowing the study of premalignant and malignant liver lesions and the evaluation of new therapeutic strategies. Here, we review recent advances in GEM models of HCC with an emphasis on new technologies

Increased Susceptibility of Mycobacterium tuberculosis to Ethionamide by Expressing PPs-Induced Rv0560c

Tuberculosis, an infectious disease, is one of the leading causes of death worldwide. Drug-resistant tuberculosis exacerbates its threat. Despite long-term and costly treatment with second-line drugs, treatment failure rates and mortality remain high. Therefore, new strategies for developing new drugs and improving the efficiency of existing drug treatments are urgently needed. Our research team reported that PPs, a new class of potential anti-tuberculosis drug candidates, can inhibit the growth of drug-resistant Mycobacterium tuberculosis. Here, we report a synergistic effect of PPs with ethionamide (ETH), one of the second-line drugs, as a result of further research on PPs. While investigating gene expression changes based on microarray and 2DE (two-dimensional gel electrophoresis), it was found that PPs induced the greatest overexpression of Rv0560c in M. tuberculosis. Based on this result, a protein microarray using Rv0560c protein was performed, and it was confirmed that Rv0560c had the highest interaction with EthR, a repressor for EthA involved in activating ETH. Accordingly, a synergistic experiment was conducted under the hypothesis of increased susceptibility of ETH to M. tuberculosis by PPs. As a result, in the presence of 0.5&times; MIC PPs, ETH showed a growth inhibitory effect on drug-sensitive and -resistant M. tuberculosis even at a much lower concentration of about 10-fold than the original MIC of ETH. It is also suggested that the effect was due to the interaction between PPs and Rv2887, the repressor of Rv0560c. This effect was also confirmed in a mouse model of pulmonary tuberculosis, confirming the potential of PPs as a booster to enhance the susceptibility of M. tuberculosis to ETH in treating drug-resistant tuberculosis. However, more in-depth mechanistic studies and extensive animal and clinical trials are needed in the future

Tailoring the density of carbon nanotube networks through chemical self-assembly by click reaction for reliable transistors

Semiconducting single-walled carbon nanotubes (sc-SWNTs) are attracting considerable interest for use as active layers in various electronic applications such as field-effect transistors (FETs) because of their extremely high intrinsic charge carrier mobility and solution processability at low costs. However, it is challenging to achieve a constant sc-SWNT density for ensuring commercial-level, uniform performance in FETs based on random -network SWNT films formed by solution processing. This paper reports a facile method for sorting sc-SWNT and precisely controlling the density of random-network sc-SWNT films by azide-functionalized polymer. The chemical self-assembly of SWNTs is performed between azide-functionalized polymer-wrapped sc-SWNTs and alkyne-based substrate via click reaction. A high-purity sc-SWNT ink is obtained by the conjugated polymer wrapping method using an azide-functionalized polyfluorene in methylcyclohexane. The sc-SWNTs are then chemically bound to a substrate with an alkyne adhesive layer through a Cu-catalyzed azide-alkyne cycloaddi-tion reaction. FETs with dense and uniform SWNT films with a linear density of 30 (+/- 2) tubes mu m- 1 exhibit markedly high hole mobility of up to 25.4 cm2 V-1 s-1 and excellent performance uniformity. Furthermore, the SWNT films anchored on the substrates are highly resistant to exogenous disruptions, such as sonication in organic solvents, leading the great potential for applications such as biosensors that require strong adhesive strength

Hidden surface channel in two-dimensional multilayers

International audienceAbstract Numerous carrier scatterers, such as atomic defects, fixed oxide charges, impurities, chemical residues, and undesired surface adsorbates, including oxygen and water molecules, strongly degrade the carrier mobility of atomically thin two-dimensional (2D) materials. However, the effect of surface adsorbates and surface oxidation on the carrier density profile along the thickness of 2D multilayers is not well known, particularly for a substantial interruption in the formation of the top-surface channel. Here, we uncover a hidden surface channel in p-type black phosphorus and n-type rhenium disulfide multilayers originating from undesired ambient adsorbates and surface oxides that not only populate hole density (or reduce electron density) but also suppress carrier mobility. The absence of a second peak in the transconductance curve under ambient conditions indicates the disappearance of the top-surface channel inside the 2D multilayers, which is a possible indicator for the cleanliness of the top surface and can be used in gas sensor applications. Moreover, the negligible variation in the drain bias polarity-dependent turn-on voltage for the bottom channel under ambient conditions validates the exclusive contribution of surface adsorbates to the formation of the top channel in 2D multilayers. Our results provide a novel insight into the distinct carrier transport in 2D optoelectronic devices and diverse sensors