Impaired hydrogen sulfide protein expression in patients with peripheral artery disease

INTRODUCTION: Hydrogen sulfide (H2S) is a gaseous signaling molecule that serves various roles in the vasculature, such as upregulating angiogenesis, vascular smooth muscle relaxation, protecting endothelial function, and regulating redox balance. Despite H2S’s positive impacts on vascular homeostasis, it is important to note that its actions depend on its concentrations. At high concentrations, H2S has been reported to increase oxidative stress damage, such as oxidation of cysteine residues and lipid peroxidation. This may indicate that H2S may act as a ‘double-edged sword’ in the field of vascular physiology. Peripheral artery disease (PAD) is an atherosclerotic disease which manifested by claudication (leg pain during walking). Growing evidence suggests that abnormal H2S level may present with vascular diseases, however, only a few animal studies investigated the H2S and H2S -mediated oxidative stress damage in vascular disease models, and there are currently no available studies for human vascular disease patients, such as patients with PAD. Therefore, the purpose of this study was to examine the H2S and oxidative stress damage in peripheral blood mononuclear cells (PBMCs) and skeletal muscle tissues from patients with PAD. METHODS: Western blot was performed using skeletal muscle tissues and PBMCs to examine protein expression of cystathionase (CTH), which catalyzes production of H2S, and glutathione peroxidase-4 (GPx-4) and catalase (CAT), which are antioxidant markers, from healthy adults (CON) and patients with PAD (PAD). RESULTS: Patients with PAD show a lower expression of CTH compared to CON (P \u3c 0.01, PAD: 1.61 ± 0.44, CON: 8.53 ± 0.46). However, CAT expression was not different between groups (P = 0.429, PAD: 0.03 ± 0.02, CON: 0.01 ± 0.01). In addition, CAT and GPx-4 expression was assessed in CON PBMCs (CAT: 5.07 ± 1.14, GPx-4: 0.63 ± 0.3). CONCLUSION: CTH protein expression in the skeletal muscle is attenuated in PAD compared to CON. However, CAT protein expression in the skeletal muscle is not different between groups. These data suggest an impairment is present in the H2S signaling system in the skeletal muscle of patients with PAD

Regularity for Solutions of Second-Order Nonlinear Integrodifferential Functional Equations

We deal with the well-posedness for solutions of nonlinear integrodifferential equations of second-order in Hilbert spaces by converting the problem into the contraction mapping principle with more general conditions on the principal operators and the nonlinear terms and obtain a variation of constant formula of solutions of the given nonlinear equations

Inhibitory Effects of Hwangryunhaedok-Tang in 3T3-L1 Adipogenesis by Regulation of Raf/MEK1/ERK1/2 Pathway and PDK1/Akt Phosphorylation

Hwangryunhaedok-tang (HRT) has been long used as traditional medicine in Asia. However, inhibitory role of HRT is unclear in early stage of 3T3-L1 adipocyte differentiation related to signaling. In the present study, we investigated the inhibitory effects of HRT on upstream signaling of peroxisome proliferation-activity receptor-γ (PPAR-γ) and CCAAT/enhancer binding protein-β (C/EBP-β) expression in differentiation of 3T3-L1 preadipocytes. We found that HRT significantly inhibited the adipocyte differentiation by downregulating several adipocyte-specific transcription factors including PPAR-γ, C/EBP-α, and C/EBP-β in 3T3-L1 preadipocytes. Furthermore, we observed that HRT markedly inhibited the differentiation media-mediated phosphorylation of Raf/extracellular mitogen-activated protein kinase 1 (MEK1)/signal-regulated protein kinase 1/2 (ERK1/2) and phosphorylation of phosphoinositide-dependent kinase 1 (PDK1)/Akt. These results indicate that anti-adipogenesis mechanism involves the downregulation of the major transcription factors of adipogenesis including PPAR-γ and C/EBP-α through inhibition of Raf/MEK1/ERK1/2 phosphorylation and PDK1/Akt phosphorylation by HRT. Furthermore, high performance liquid chromatography (HPLC) analysis showed HRT contains active antiobesity constituents such as palmatine, berberine, geniposide, baicalin, baicalein, and wogonin. Taken together, this study suggested that anti-adipogenesis effects of HRT were accounted by downregulation of Raf/MEK1/ERK1/2 pathway and PDK1/Akt pathway during 3T3-L1 adipocyte differentiation

STATIC AND DYNAMIC CHARACTERISTICS OF AIR FOIL THRUST BEARING CONSIDERING TILTING PAD CONDITION

ABSTRACT The thrust pad of the rotor is used to sustain the axial force generated due to the pressure difference between the compressor and turbine sides of turbomachinery such as the gas turbines and turbochargers. Furthermore, this thrust pad has a role to maintain and determines the attitude of the rotor. In a real system, it also helps reinforce the stiffness and damping of the journal bearing. This study was performed for the purpose of analyzing the characteristics of the air foil thrust bearing. The model for the air foil thrust bearing used in this study is composed of two parts: one is an inclined plane, which plays a role to increase the load carrying capacity using the physical wedge effect, and the other is a flat plane. This study mainly consists of three parts. First, the static characteristics were obtained over the region of the thin air film using the finite difference method (FDM) and the bump foil characteristics using the finite element method (FEM). Second, the analysis of the dynamic characteristics was conducted by perturbation method. For more exact calculation, the rarefaction gas coefficients perturbed about the pressure and film thickness were taken into consideration. At last, the static and dynamic characteristics of the tilting condition of the thrust pad were obtained. Furthermore, the load carrying capacity and torque were calculated for both tilting and not-tilting conditions. From this study, several results were presented: 1) the stiffness and damping of the bump foil under the condition of the various bump parameters, 2) the load carrying capacity and bearing torque at the tilting state, 3) the bearing performance under various bearing parameters, 4) the effects considering the rarefaction gas coefficients

CRISPR RNAs trigger innate immune responses in human cells

Here, we report that CRISPR guide RNAs (gRNAs) with a 5'-triphosphate group (5'-ppp gRNAs) produced via in vitro transcription trigger RNA-sensing innate immune responses in human and murine cells, leading to cytotoxicity. 5'-ppp gRNAs in the cytosol are recognized by DDX58, which in turn activates type I interferon responses, causing up to similar to 80% cell death. We show that the triphosphate group can be removed by a phosphatase in vitro and that the resulting St-hydroxyl gRNAs in complex with Cas9 or Cpfl avoid innate immune responses and can achieve targeted mutagenesis at a frequency of 95% in primary human CD4(+) T cells. These results are in line with previous findings that chemically synthesized sgRNAs with a 5'-hydroxyl group are much more efficient than in vitro-transcribed (IVT) sgRNAs in human and other mammalian cells. The phosphatase treatment of IVT sgRNAs is a cost-effective method for making highly active sgRNAs, avoiding innate immune responses in human cells.

The Influence of Pain Sensitivity on the Symptom Severity in Patients with Lumbar Spinal Stenosis

Background: The symptom severity of back pain/leg pain is not correlated with the severity of degenerative changes and canal stenosis in lumbar stenosis. Considering the individual pain sensitivity might play an important role in pain perception, this discordance between the radiologic findings and clinical symptoms in degenerative lumbar stenosis might originate from the individual difference of pain sensitivity for back pain and/or leg pain.Objective: To determine the relationship among the clinical symptoms, radiologic findings, and the individual pain sensitivity in the patients with degenerative lumbar spinal stenosis.Study Design: Retrospective analysis of prospectively collected data.Setting: A spine center in the department of orthopedic surgery.Methods: In 94 patients who had chronic back pain and/or leg pain caused by degenerative lumbar spinal stenosis, a medical history, a physical examination, and completion of a series of questionnaires, including pain sensitivity questionnaire (PSQ) [total PSQ and PSQ-minor], Oswestry Disability Index (ODI), Visual Analog Pain Scale (VAS) for back pain, and Short Form-36 (SF-36) were recorded on the first visit. Radiologic analysis was performed using the MRI findings. The grading of canal stenosis was based on the method by Schizas, and the degree of disc degeneration was graded from T2-weighted images with the Pfirrmann classification. The correlations among variables were statistically analyzed.Results: Total PSQ and PSQ-minor were not dependent on the grade of canal stenosis after gender adjustment. VAS for leg pain and back pain was highly associated with the total PSQ and the PSQ-minor. Total PSQ and PSQ-minor were also significantly associated with ODI. Among SF-36 scales, the PSQ minor had significant correlations with SF-36 such as bodily pain (BP), Role-emotional (RE), and Mental Component Summary (MCS) after control of confounding variables such as body mass index (BMI), age, and the grade of canal stenosis/disc degeneration. Total PSQ was significantly associated with the SF-36 RP, BP, and RE. Furthermore, after adjustment for gender and pain sensitivity, there was no significant association between the grade of canal stenosis and VAS for back pain/leg pain and ODI, and no correlation was found between the grade of disc degeneration and VAS for back pain/leg pain and ODI, either.Limitations: The multiple lesions of canal stenosis and/or disc degeneration and the grade of facet degeneration were not considered as a variable.Conclusion: The current study suggests that the pain sensitivity could be a determining factor for symptom severity in the degenerative spinal disease.OAIID:oai:osos.snu.ac.kr:snu2013-01/102/0000004226/3SEQ:3PERF_CD:SNU2013-01EVAL_ITEM_CD:102USER_ID:0000004226ADJUST_YN:YEMP_ID:A076317DEPT_CD:801CITE_RATE:10.722FILENAME:E046T_PainPhysician_Kim_The Influence of Pain Sensitivity on the Symptom Severity.pdfDEPT_NM:의학과EMAIL:[email protected]_YN:YCONFIRM: