Int J Med Sci
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Background: To maintain the normal pregnancy, suppression of inflammatory signaling pathway is a crucial physiologic response. Dexmedetomidine has been used for labor analgesia or supplement of inadequate regional analgesia during delivery. And it has been reported that dexmedetomidine has an anti-inflammatory effect. ⋯ The activation of p38 and NF-κB was suppressed by dexmedetomidine pretreatment in LPS-treated WISH cells. Conclusion: We demonstrated that dexmedetomidine pretreatment suppressed the expressions of inflammatory mediators increased by LPS. In addition, this study suggests that anti-inflammatory effect of dexmedetomidine on WISH cells was mediated by the inhibitions of p38 and NF-κB activation.
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Background: Fatty acid-binding protein 1 (FABP1) (also known as liver-type fatty acid-binding protein or LFABP) is a protein that is mainly expressed in the liver, and is associated with hepatocyte injury in acute transplant rejection. Reduced levels of FABP1 in mice livers have been shown to be effective against nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the association between plasma FABP1 levels and NAFLD in patients with type 2 diabetes mellitus (T2DM). ⋯ The odds ratio (OR) for the risk of overt NAFLD with increasing levels of sex-specific FABP1 was significantly increased (OR 2.63 [95% CI 1.30-5.73] vs. 4.94 [2.25-11.48]). The OR in the second and third tertiles of FABP1 remained significant after adjustments for BMI, triglycerides, high-density lipoprotein cholesterol, HbA1C, homeostasis model assessment estimate of insulin resistance, white blood cell count, hepatic enzymes, and eGFR. Conclusion: Our results indicate that FABP1 may play a role in the pathogenesis of NAFLD in patients with T2DM.
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Amyotrophic lateral sclerosis (ALS) is a serious disease characterized by the degeneration of motor neurons resulting in muscle weakness and paralysis. The neuroendocrine polypeptide VGF is localized in the central nervous system and peripheral endocrine neurons and is cleaved into several polypeptides with multiple functions. Previous studies revealed that VGF was decreased in the cerebrospinal fluid of ALS model mice and sporadic ALS patients. ⋯ We revealed that VGF protein level was decreased in the anterior horn of ALS patients; however, the expression level of VGF protein was not changed in the posterior horn or white matter. Furthermore, the expression level of VGF protein was conserved in ALS patients with long-term survival. These results reveal that VGF is mainly supplied by human motor neurons, and suggest that VGF expression changes may be involved in ALS pathology.
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The PB2 protein of the influenza virus RNA polymerase is a major virulence determinant of influenza viruses. It binds to the cap structure at the 5' end of host mRNA to generate short capped RNA fragments that are used as primers for viral transcription named cap-snatching. A large number of the compounds were shown to bind the minimal cap-binding domain of PB2 to inhibit the cap-snatching machinery. ⋯ A previous study reported some promising compounds including azaindole and hydroxymethyl azaindole, which were analyzed here to predict binding affinity to PB2 protein using the steered molecular dynamics (SMD) and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) methods. The results show that the rupture force (Fmax) value of three complexes is in agreement with the binding free energy value (ΔGbind) estimated by the MM-PBSA method, whereas for the non-equilibrium pulling work (Wpull) value a small difference between A_PB2-4 and A_PB2-12 was observed. The binding affinity results indicate the A_PB2-12 complex is more favorable than the A_PB2-4 and A_PB2-16 complexes, which means the inhibitor (12) has the potential to be further developed as anti-influenza agents in the treatment of influenza A.
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Background: Kidney renal clear cell carcinoma (KIRC) is the most representative subtype of renal cancer. Immune infiltration was associated with the survival time of patients with tumors. C-C chemokine ligand 5 (CCL5) can promote the malignant process of tumor and be related to infiltration immune cells in some cancers, but not reported in KIRC. ⋯ Conclusion: The increased expression of CCL5 is related to poor prognosis and clinical features. Meanwhile, CCL5 is related to Tregs ratios and CCL5 may act as a typical chemokine to recruit Tregs in KIRC. CCL5 could be used as a biomarker for the prognosis prediction and a potential therapeutic target for patients with KIRC.