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Background/purpose: Oral submucous fibrosis (OSF) has been regarded as a premalignant disorder of oral cancer, and myofibroblasts are the main cells that are responsible for pathological fibrosis. Hence, elucidation of the molecular mechanism underlying myofibroblast activation is important to treat OSF. MicroRNA-21 (miR-21) is a well-known fibrosis non-coding RNA, and its role in the development of OSF remains largely unclear. Materials and methods: Luciferase reporter assay was used to confirm the direct interaction between miR-21 and its target programmed cell death 4 (PDCD4). The expression level of PDCD4 in OSF was examined by qRT-PCR. Myofibroblast activities were assessed by collagen gel contraction and transwell migration assays. Results: Our result validated the direct binding of miR-21 to PDCD4. We showed the expression of PDCD4 was downregulated in OSF specimens and negatively correlated with miR-21. Our results suggested that overexpression of PDCD4 in fibrotic buccal mucosal fibroblasts (fBMFs) mitigated the myofibroblast activities, including collagen gel contractility and migration capacity. Moreover, we showed miR-21 contributed to myofibroblast activation of BMFs through repression of PDCD4. Conclusion: Our results suggest that the miR-21/PDCD4 axis mediates the myofibroblast activation of BMFs, and targeting this axis may exert an anti-fibrosis effect.

A discovery that cells die of a novel and distinctive process, along with some characteristic events, such as cellular shrinkage and Programmed cell death 4 disappearance, has been done by using non-thermal atmospheric pressure plasma-activated solutions [1]. Data on the responsiveness of multiple cell types to the induction of cellular shrinkage and cell death and the loss of Programmed cell death 4 by exposure to the non-thermal atmospheric pressure plasma-activated solutions were collected. Human neuroblastoma SH-SY5Y cells, murine myoblast C2C12 cells, and murine embryonic fibroblasts were cultured for various periods in each of the non-thermal atmospheric pressure plasma-activated solutions and then examined by light field microscopic observation for their effects on cell morphology, by Trypan blue dye exclusion assay for those on cell death, and by Western blotting for those on Programmed cell death 4 disappearance. The data clarified some differences in the responsiveness to the induction of cellular shrinkage, cell death, and Pdcd4 disappearance by all the non-thermal atmospheric pressure plasma-activated solutions among the cells.

Introduction: Gestational trophoblastic disease (GTD) encompasses a range of trophoblastic disorders from hydatidiform mole (HM), to malignant gestational trophoblastic neoplasia (GTN). The exact molecular mechanisms of GTN remain unknown. Dysregulation and dysfunction of programmed cell death 4 (PDCD4)have been observed in many cancers. The roles of PDCD4 in GTD have not been previously reported., Methods: A total of 161 cases of formalin-fixed, paraffin-embedded trophoblast blocks, and 36 cases of fresh trophoblast tissues were collected, including normal first trimester placentas, HM, and invasive HM. Choriocarcinoma cells JAR and JEG-3 were employed. The expressions of PDCD4 and small ubiquitin-like modifier 2/3 (SUMO2/3) were examined by immunohistochemistry, quantitative reverse transcription PCR and Western blotting in trophoblastic tissues and cells. The relationship between SUMOylation and PDCD4 was investigated. The effects of PDCD4 on proliferation, invasion, and migration of choriocarcinoma cells were evaluated by Cell Counting Kit-8 and transwell assays post siRNA transfection. Extracellular Matrix & Adhesion Profiler PCR Array was used to screen the downstream molecules of PDCD4., Results: PDCD4 was significantly repressed in HM tissues. Loss of PDCD4 expression was demonstrated in 90% invasive HMs. Choriocarcinoma cells also displayed with suppressed PDCD4 expression. The varied expression of PDCD4 was paralleled by SUMO2/3. Inhibition of SUMOylation reduced the expression of PDCD4. Silencing of PDCD4promoted proliferation/migration/invasion, upregulatedMMP3/MMP8/ITGB2, and downregulated TIMP1/TIMP2 in choriocarcinoma cells., Discussion: Our results suggest that reduced SUMOylation is one reason for suppressed PDCD4 in GTD. Loss of PDCD4 likely determines the malignant phenotype of GTN by dysregulating some members of the MMPs/TIMPs/integrins complex., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: In this study, we explore the effects of pretreatment with atorvastatin on the cardiac function of piglets after coronary microembolization (CME)., Methods: Twenty Bama miniature pigs were randomized to sham surgery group (sham group), CME Group, conventional dose group and intensive-dose group, with 5 miniature pigs in each group. Pigs in the CME group received a total dosage of 100,000 microspheres (42 μm) suspended in 10 ml normal saline within 40 min, while animals in the sham group received the same dosage of normal saline. In the conventional dose group, atorvastatin (1.5mg/kg) was given once daily starting 7d before microembolization. In the intensive-dose group, atorvastatin (1.5mg/kg) was also given once daily 7d before intervention, and an additional 3mg/kg 4h before percutaneous coronary intervention. Cardiac function indices were determined by echocardiography; and infarct size was determined histopathologically. PDCD4 mRNA and TNF-α mRNA and protein expression were evaluated by quantitative fluorescence-polymerase chain reaction and Western blot, respectively. NF-κB activation was evaluated by electrophoretic mobility shift assay., Results: (1) Cardiac function was significantly lower (P<0.05) in CME group compared with the sham group. CME reduced myocardial systolic dysfunction and left ventricular dilatation. The conventional and intensive-dose groups showed improved CME-induced cardiac function when compared with the CME Group (P<0.05). (2) Compared with the conventional group, the dose-intensive group showed lower PDCD4 and TNF-α expression and NF-κB activation as well as improved cardiac function (P<0.05)., Conclusions: Atorvastatin effectively improved CME-induced cardiac damage with intensive-dose therapy showing better outcome. The protective effects are mediated via suppression of PDCD4/NF-κB/TNF-α signaling in cardiomyocytes., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Protein synthesis and degradation are dynamically regulated processes that act in concert to control the accretion or loss of muscle mass. The present article focuses on the mechanisms involved in the impairment of protein synthesis that are associated with skeletal muscle atrophy. The vast majority of mechanisms known to regulate protein synthesis involve modulation of the initiation phase of mRNA translation, which comprises a series of reactions that result in the binding of initiator methionyl-tRNAi and mRNA to the 40S ribosomal subunit. The function of the proteins involved in both events has been shown to be repressed under atrophic conditions such as sepsis, cachexia, chronic kidney disease, sarcopenia, and disuse atrophy. The basis for the inhibition of protein synthesis under such conditions is likely to be multifactorial and includes insulin/insulin-like growth factor 1 resistance, pro-inflammatory cytokine expression, malnutrition, corticosteroids, and/or physical inactivity. The present article provides an overview of the existing literature regarding mechanisms and signaling pathways involved in the regulation of mRNA translation as they apply to skeletal muscle wasting, as well as the efficacy of potential clinical interventions such as nutrition and exercise in the maintenance of skeletal muscle protein synthesis under atrophic conditions. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Various human cardiovascular pathophysiological conditions associate aberrant expression of microRNAs (miRNAs) and circulating miRNAs are emerging as promising biomarkers. In mice, myocardial miR-21 overexpression is related to cardiac fibrosis elicited by pressure overload. This study was designed to determine the role of myocardial and plasmatic miR-21 in the maladaptive remodeling of the extracellular matrix induced by pressure overload in aortic stenosis (AS) patients and the clinical value of miR-21 as a biomarker for pathological myocardial fibrosis., Methods: In left ventricular biopsies from 75 AS patients and 32 surgical controls, we quantified the myocardial transcript levels of miR-21, miR-21-targets and ECM- and TGF-β-signaling-related elements. miR-21 plasma levels were determined in 25 healthy volunteers and in AS patients. In situ hybridization of miR-21 was performed in myocardial sections., Results: The myocardial and plasma levels of miR-21 were significantly higher in the AS patients compared with the controls and correlated directly with the echocardiographic mean transvalvular gradients. miR-21 overexpression was confined to interstitial cells and absent in cardiomyocytes. Using bootstrap validated multiple linear regression, the variance in myocardial collagen expression was predicted by myocardial miR-21 (70% of collagen variance) or plasma miR-21 (52% of collagen variance), together with the miR-21 targets RECK and PDCD4, and effectors of TGF-ß signaling., Conclusions: Our results support the role of miR-21 as a regulator of the fibrotic process that occurs in response to pressure overload in AS patients and underscore the value of circulating miR-21 as a biomarker for myocardial fibrosis., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)