No abstract

Emerging evidence suggested that circular RNAs (circRNAs) play critical roles in cervical cancer (CC) progression. However, the roles and molecular mechanisms of hsa_circ_0007364 in the tumorigenesis of CC remain unclear. In the present study, we used bioinformatics analysis and a series of experimental analysis to characterize a novel circRNA, hsa_circ_0007364 was upregulated and associated with advanced clinical features in CC patients. Hsa_circ_0007364 inhibition notably suppressed the proliferation and invasion abilities of CC cells in vitro and reduced tumor growth in vivo. Moreover, hsa_circ_0007364 was uncovered to sponge miR-101-5p. Additionally, methionine adenosyltransferase II alpha (MAT2A) was verified as a target gene of miR-101-5p, and its downregulation reversed the inhibitory effects of hsa_circ_0007364 knockdown on CC progression. Therefore, we suggested that hsa_circ_0007364 might serve as an oncogenic circRNA in CC progression by regulating the miR-101-5p/MAT2A axis, which provides a potential therapeutic target to the treatment. Research highlights (1) hsa_circ_0007364 was upregulated in CC (2) hsa_circ_0007364 promoted CC cell progression (3) hsa_circ_0007364/miR-101-5p/MAT2A axis in CC ARTICLE HISTORY

Hepatocellular carcinoma (HCC) is the leading cause of cancer related death worldwide. The number of deaths is proportional to the global incidence, which highlights the aggressive tumor biology and lack of effective therapies. Dysregulation of microRNAs has been implicated in carcinogenesis and progression of liver cancer. Here, we identified that miR-1258 was significantly downregulated in HCC and associated with poor patients' survival. Overexpression of miR-1258 significantly inhibits liver cancer cell growth, proliferation and tumorigenicity through increasing cell cycle arrest in G0/G1 phase and promotes cell apoptosis. Interestingly, stable overexpression of miR-1258 suppresses cell migration, stemness and increases sensitivity of HCC cells to chemotherapy drug like doxorubicin. The CDC28 protein kinase regulatory subunit 1B (CKS1B) was identified as a functional downstream target of miR-1258. Re-expression of CKS1B overcomes miR-1258 induced apoptosis and increases stemness of HCC cells, suggesting that loss of miR-1258 contributes to carcinogenesis and progression of liver cancer through targeting CKS1B. Therefore, loss of miR-1258 may be a potential diagnostic and prognostic biomarker and blocking miR-1258-CKS1B axis is a potential therapeutic strategy in HCC.

Our previous study confirmed that cardiopulmonary bypass (CPB) leads to acute lung injury (ALI) via inducing high-mobility group box 1 (HMGB1) release. Recent research showed that HMGB1 promotes pulmonary injury mainly via exosomes transport. Currently, alveolar epithelial cell (AEC) necroptosis has been demonstrated to be involved in ALI. However, it is unknown whether exosomal inflammatory cytokine HMGB1 promotes ALI by inducing AEC necroptosis, and its underlying mechanisms remain elusive. Here, a prospective cohort study was carried out, in which plasma samples from 21 CPB patients were isolated at four specific time points: pre-CPB, 2, 12, and 24 h after initiation of CPB. Plasma exosomes were extracted via ultra-high-speed centrifugation and cocultured with AEC cell line-A549 cells at increasing concentrations of 50, 100, and 150 μg/mL. Then, HMGB1 antagonist-Box A and mtDNA deficiency ethidium bromide (EtBr) were applied to explore the underlying role of exosomal HMGB1 and cytoplasm mitochondrial DNA in AEC. Western blot analysis showed that plasma exosomal HMGB1 expression gradually increased and peaked at 24 h after CPB. Twenty-four-hour treatment of CPB-derived exosomes at 150 μg/mL for 24 h could induce necroptosis by promoting mitochondrial fission and further elevating cytoplasm mtDNA levels in A549 cells, which was successfully blocked by Box A or EtBr. Most importantly, EtBr significantly inhibited cytoplasm mtDNA downstream guanosine monophosphate (GMP)-AMP synthase (cGAS)/stimulator of interferon gene (STING) signal pathway. Collectively, these data demonstrate that CPB-derived plasma exosomal HMGB1 contributes to AEC necroptosis through the mtDNA/cGAS/STING pathway.

Purpose Congenitally corrected transposition of the great arteries (ccTGA) is a rare disease that is complicated by a variety of tachyarrhythmias or atrioventricular blocks and cardiac malformations. Anesthesia management is a challenge, especially in ccTGA patients with complications. Herein, we reported a case of ccTGA. Methods Multimodal general anesthesia combined with transversus thoracic muscle plane block (TTMPB), use of low-dose opioids and adjuvant medications, lung protective ventilation, use of vasoactive drugs and close perioperative monitoring were employed for the peri-operative management of this patient. Results The patient was safely returned to the ward and did not develop serious complications. Fourteen days after surgery, the patient recovered well and was discharged. Conclusions For patients undergoing a secondary cardiac surgery for ccTGA, preoperative evaluation of etiology of ccTGA is very important. Anesthesia management based on the surgical method and intraoperative vital signs and the postoperative real-time monitoring are also crucial for the post-operative recovery of these patients.