Oral Administration of Escin Inhibits Acute Inflammation and Reduces Intestinal Mucosal Injury in Animal Models

The present study aimed to investigate the effects of oral administration of escin on acute inflammation and intestinal mucosal injury in animal models. The effects of escin on carrageenan-induced paw edema in a rat model of acute inflammation, cecal ligation and puncture (CLP) induced intestinal mucosal injury in a mouse model, were observed. It was shown that oral administration of escin inhibits carrageenan-induced paw edema and decreases the production of prostaglandin E2 (PGE2) and cyclooxygenase- (COX-) 2. In CLP model, low dose of escin ameliorates endotoxin induced liver injury and intestinal mucosal injury and increases the expression of tight junction protein claudin-5 in mice. These findings suggest that escin effectively inhibits acute inflammation and reduces intestinal mucosal injury in animal models

Network Pharmacology Based Research on the Combination Mechanism Between Escin and Low Dose Glucocorticoids in Anti-rheumatoid Arthritis

Rheumatoid arthritis (RA) is characterized by chronic progressive symmetrical synovitis and destruction of multiple joints. Glucocorticoids (GCs) are widely used in the treatment of RA. However, their adverse effects can be serious. Escin, which is isolated from Aesculus hippocastanum L., has been reported to have anti-inflammatory effects. We investigated the anti-RA effect of Escin combined with low dose GCs (dexamethasone, Dex) and the underlying mechanism. Adjuvant-induced RA rats and lipopolysaccharides (LPS)-injured RAW264.7 cells were used to investigate the anti-RA effects of Escin combined with low dose Dex in vivo and in vitro. The results showed that Escin combined with low-dose Dex significantly decreased arthritic index, serum IL-6 and TNF-α levels, reduced paw swelling, and ameliorated the joint pathology and immune organ pathology. Gene chip results revealed that Nr3c1 (GR) expression was significantly altered, and that GR was activated by Escin and low dose Dex in vivo and in vitro. Additionally, Escin combined with low dose Dex also significantly increased GR mRNA expression. However, when GR expression was suppressed by its specific inhibitor, the anti-RA effect of Escin combined with low-dose Dex was abolished. The data in this study demonstrated that Escin combined with Dex reduced the dose of Dex, and exerted significant anti-RA effects, which could also reduce the adverse effects of Dex. This combination might result from GR activation. This study might provide a new combination of drugs for the treatment of RA

Characterization of an aspartate aminotransferase encoded by YPO0623 with frequent nonsense mutations in Yersinia pestis

Yersinia pestis, the causative agent of plague, is a genetically monomorphic bacterial pathogen that evolved from Yersinia pseudotuberculosis approximately 7,400 years ago. We observed unusually frequent mutations in Y. pestis YPO0623, mostly resulting in protein translation termination, which implies a strong natural selection. These mutations were found in all phylogenetic lineages of Y. pestis, and there was no apparent pattern in the spatial distribution of the mutant strains. Based on these findings, we aimed to investigate the biological function of YPO0623 and the reasons for its frequent mutation in Y. pestis. Our in vitro and in vivo assays revealed that the deletion of YPO0623 enhanced the growth of Y. pestis in nutrient-rich environments and led to increased tolerance to heat and cold shocks. With RNA-seq analysis, we also discovered that the deletion of YPO0623 resulted in the upregulation of genes associated with the type VI secretion system (T6SS) at 26°C, which probably plays a crucial role in the response of Y. pestis to environment fluctuations. Furthermore, bioinformatic analysis showed that YPO0623 has high homology with a PLP-dependent aspartate aminotransferase in Salmonella enterica, and the enzyme activity assays confirmed its aspartate aminotransferase activity. However, the enzyme activity of YPO0623 was significantly lower than that in other bacteria. These observations provide some insights into the underlying reasons for the high-frequency nonsense mutations in YPO0623, and further investigations are needed to determine the exact mechanism

Jieyu Anshen Granule, a Chinese Herbal Formulation, Exerts Effects on Poststroke Depression in Rats

Jieyu Anshen granule (JY) is a traditional Chinese medicine formula for treating depression and anxiety. The aim of the study was to observe the effects of JY on poststroke depression (PSD) and investigate the underlying mechanism. PSD rat model was developed by middle cerebral artery occlusion following chronic unpredictable mild stress in conjunction with isolation rearing. We performed behavioral tests, Western blot, ELISA, and BrdU/NeuN staining. Treatment with JY showed significant antidepressant effect in open-field and sucrose preference tests, as well as significant improvement in beam-walking, cylinder, grip strength, and water maze tests. In addition, treatment with JY could restore the levels of neurotransmitters and decrease the levels of hormone and inflammation cytokines in serum and brain. Treatment with JY also showed significant regulation in the expression of neurotransmitter receptors and NF-κB/IκB-α signaling in the prefrontal cortex and hippocampus. Moreover, the numbers of newborn neurons in the hippocampus were increased by treatment with JY. Our results suggest that JY could ameliorate PSD and improve the neurological and cognitive functions. The antidepressive effect may be associated with the modulation of JY on monoamine system, neuroendocrine, neuroinflammation, and neurogenesis

Microstructure features induced by fatigue crack initiation up to very-high-cycle regime for an additively manufactured aluminium alloy

Fatigue failure can still occur beyond 10(7) cycles, i.e. very-high-cycle fatigue (VHCF), in many metallic materials, such as aluminium alloys and high-strength steels. For VHCF of high-strength steels, a fine granular area (FGA) surrounding an inclusion is commonly identified as the characteristic region of crack initiation on the fracture surface. However, no such FGA feature and related crack initiation behaviour were observed in VHCF of conventionally cast or wrought aluminium alloys. Here, we first reported the distinct mechanisms of crack initiation and early growth, namely the microstructure feature and the role of FGA in VHCF performance for an additively manufactured (AM) AlSi10Mg alloy. The AM pores play a key role in fatigue crack initiation similar to that of the inclusions in high-strength steels, resulting in almost identical FGA behaviour for different materials under a range of mean stress with a stress ratio at R 0. The profile microstructure of FGA is identified as a nanograin layer with Si rearrangement and grain boundary transition. This process consumes a large amount of cyclic plastic energy making FGA undertake a vast majority of VHCF life. These results will deepen the understanding of VHCF nature and shed light on crack initiation mechanism of other aluminium and AM alloys. (c) 2023 Published by Elsevier Ltd on behalf of The editorial office of Journal of Materials Science & Technology

Influence of processing parameters of selective laser melting on high-cycle and very-high-cycle fatigue behaviour of Ti-6Al-4V

Orthogonal experiment design together with the analysis of variance was used to examine the processing parameters (laser power, scan speed, layer thickness and hatch spacing) of selective laser melting (SLM) for superior properties of SLM parts, in which nine groups of specimens of Ti-6Al-4V were fabricated. The results clarify that the influence sequence of individual parameter on the porosity is laser power > hatch spacing > layer thickness > scan speed. Ultrasonic fatigue tests (20 kHz) were conducted for the SLMed specimens in highcycle fatigue (HCF) and very-high-cycle fatigue (VHCF) regimes. The S-N data show that the fatigue strength is greatly affected by the porosity: the group with the smallest porosity percentage having the highest fatigue strength in HCF and VHCF regimes. Then, the tests on the validation group were performed to verify the optimal combination of SLM processing parameters. Moreover, the observations by scanning electron microscopy revealed that fatigue cracks initiate at lack-of-fusion defects in the cases of surface and internal crack initiation

Crack initiation mechanisms under two stress ratios up to very-high-cycle fatigue regime for a selective laser melted Ti-6Al-4V

Crack initiation mechanisms under two stress ratios (R = - 1 and 0.5) and up to very-high-cycle fatigue (VHCF) regime of a selective laser melted (SLMed) Ti-6Al-4V were investigated. Type I lack-of-fusion defects (almost equiaxed) induced crack initiation except for the cases of VHCF under R = 0.5 in which type II defects (large aspect ratio) caused facet mode crack initiation. A nanograin layer formed underneath the crack initiation region of rough area for the cases of VHCF at R = - 1, which was explained by the numerous cyclic pressing (NCP) model. A P-S-N approach was introduced to well describe the fatigue life up to VHCF regime under R = - 1 and 0.5 for the SLMed titanium alloy