No abstract

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At present, the pathogenesis of sepsis-induced myocardial dysfunction (SIMD) is not completely clear and effective treatment measures are lacking. Apelin is an endogenous ligand of the angiotensin like G protein coupled receptor APJ and a cardiovascular peptide with multiple functions. Our aim is to analyze the protective effect and mechanism of Apelin/APJ system on lipopolysaccharide (LPS)-induced myocardial dysfunction. One hour before LPS treatment, apelin-13 or an APJ antagonist [Ala]-apelin-13 (F13A) was given for pre-intervention to observe the effect of apelin-13 on cardiac ultrasound, pathological changes and inflammatory factors in LPS-treated mice. Another part of the mice was treated with apelin-13 or apelin-13 combined with F13A one hour after LPS treatment. The results showed that apelin-13 injection significantly reversed the decrease of ejection fraction and the increase of inflammatory factors induced by LPS in mice. Endogenous apelin may have protective effect on SIMD induced by LPS. Exogenous administration of apelin may inhibit LPS-induced inflammation, apoptosis and increase autophagy through TLR4/ERK1/2/NF-κB pathway.

RING finger proteins (RNFs) play a critical role in cancer initiation and progression. RNF141 is a member of RNFs family; however, its clinical significance, roles, and mechanism in colorectal cancer (CRC) remain poorly understood. Here, we examined the expression of RNF141 in 64 pairs of CRC and adjacent normal tissues by real-time PCR, Western blot, and immunohistochemical analysis. We found that there was more expression of RNF141 in CRC tissue compared with its adjacent normal tissue and high RNF141 expression associated with T stage. In vivo and in vitro functional experiments were conducted and revealed the oncogenic role of RNF141 in CRC. RNF141 knockdown suppressed proliferation, arrested the cell cycle in the G1 phase, inhibited migration, invasion and HUVEC tube formation but promoted apoptosis, whereas RNF141 overexpression exerted the opposite effects in CRC cells. The subcutaneous xenograft models showed that RNF141 knockdown reduced tumor growth, but its overexpression promoted tumor growth. Mechanistically, liquid chromatography-tandem mass spectrometry indicated RNF141 interacted with KRAS, which was confirmed by Co-immunoprecipitation, Immunofluorescence assay. Further analysis with bimolecular fluorescence complementation (BiFC) and Glutathione-S-transferase (GST) pull-down assays showed that RNF141 could directly bind to KRAS. Importantly, the upregulation of RNF141 increased GTP-bound KRAS, but its knockdown resulted in a reduction accordingly. Next, we demonstrated that RNF141 induced KRAS activation via increasing its enrichment on the plasma membrane not altering total KRAS expression, which was facilitated by the interaction with LYPLA1. Moreover, KRAS silencing partially abolished the effect of RNF141 on cell proliferation and apoptosis. In addition, our findings presented that RNF141 functioned as an oncogene by upregulating KRAS activity in a manner of promoting KRAS enrichment on the plasma membrane in CRC.

Brachial plexus avulsion (BPA), a severe acute peripheral nerve injury in adults, results in total loss of the motor function in the upper limb. Although immediate re-implantation surgery is widely performed to repair this lesion, the motor function cannot be fully restored. The main cause is that the growth velocity of axon is extremely slow in order to re-innervate the target muscles before atrophy develops. Therefore, the survival of spinal motoneurons (MNs) is considered to be a prerequisite for the recovery of motor function. The introduction of survival-proactive agents with anti-oxidative stress and anti-inflammation properties has emerged as a new approach to the motor function recovery following BPA. In the current review, we summarized the treatments of BPA in both mouse and rat models following re-implantation surgery. Furthermore, the pain treatment options following BPA were discussed.