Bezafibrate attenuates acute lung injury by preserving mitochondrial dynamics equilibrium in pulmonary epithelial cells.

Acute lung injury (ALI) serves as a common life-threatening clinical syndrome with high mortality rates, which is characterized by disturbed mitochondrial dynamics in pulmonary epithelial barrier. Peroxisome proliferator-activated receptor-γ (PPAR-γ) is one of the critical nuclear receptors, exerting important roles in preserving mitochondrial dynamics equilibrium. Previous studies have suggested that bezafibrate (BEZ), a PPAR-γ agonist, could improve obesity and insulin resistance. In the present study, we explored whether bezafibrate could attenuate lipopolysaccharide (LPS)-induced ALI in vivo and in vitro. Using C57BL/6 mice exposed to LPS, we observed that BEZ pretreatment (100 mg/kg) for 7 days decreased lung pathologic injury, reduced oxidative stress, suppressed inflammation and apoptosis, accompanied by shifting the dynamic course of mitochondria from fission into fusion. Meanwhile, we observed that BEZ could reverse the inhibition of PPAR-γ in lung tissues from LPS-treated mice. In vitro experiments also disclosed that BEZ could improve cell viability in primary pulmonary epithelial cells in a concentration-dependent manner. And BEZ (80 µM) treatment could not only inhibit oxidative stress but also preserve mitochondrial dynamics equilibrium in primary pulmonary epithelial cells. However, PPAR-γ knockdown partially abolished BEZ-mediated antioxidation and completely offset its regulatory effects on mitochondrial dynamics in primary pulmonary epithelial cells. In PPAR-γ-deficient mice, BEZ lost its pulmonary protection including anti-inflammatory and antioxidative effects in mice with ALI. Taken together, BEZ could attenuate ALI by preserving mitochondrial dynamics equilibrium in pulmonary epithelial cells in a PPAR-γ-dependent manner.

Accuracy and sensitivity of high mobility group box 1 (HMGB1) in diagnosis of acute kidney injury caused by sepsis and relevance to prognosis.

OBJECTIVE: The diagnostic value of high mobility group box 1 (HMGB1) levels in patients with acute kidney injury (AKI) caused by sepsis and its relationship with disease prognosis were investigated to improve patient survival. METHODS: A total of 120 patients diagnosed with sepsis by comprehensive clinical examination were selected as the research subjects. According to the presence or absence of concurrent AKI, all patients were divided into SIAKI (50 cases with concurrent AKI) and N-AKI groups (70 cases without concurrent AKI). Sixty normal people receiving a physical examination in our hospital during the same period were divided into the control group. The diagnostic efficacy and the influences of HMGB1 on prognosis were assessed. RESULTS: HMGB1 levels in the serum and urine of the control group (3.43 ± 0.73 pg/mL, 343.13 ± 51.03 pg/mL) were both lower than those of the SIAKI (14.76 ± 2.44 pg/mL, 1109.76 ± 225.66 pg/mL) and N-AKI groups (7.99 ± 1.84 pg/mL, 890.54 ± 97.76 pg/mL) (P < 0.05). HMGB1 in the serum of the SIAKI group was higher than that of the N-AKI group (P < 0.05). The sensitivity (88%), specificity (87%), accuracy (88%), and area under the curve (AUC) (0.891) of the joint diagnosis of HMGB1 in blood and urine were superior to the diagnostic effects of HMGB1 in serum (70%, 70%, 70%, and 0.701) and HMGB1 in urine (59%, 57%, 58%, and 0.677) (P < 0.05). The proportion of HMGB1 in the nonsurvivors was higher than that in the survivors (85%) and was obviously higher than that in the survivors (15%) (P < 0.05). CONCLUSION: As a diagnostic marker of sepsis complicated with AKI, HMGB1 in serum and urine showed good application value. Serum HMGB1 could be used to assess disease prognosis with good clinical promotion.

CircCSNK1G3 up-regulates miR-181b to promote growth and metastasis via TIMP3-mediated epithelial to mesenchymal transitions in renal cell carcinoma.

Renal cell carcinoma (RCC) is the most common form of kidney cancer, with a high recurrence rate and metastasis capacity. Circular RNAs (circRNAs) have been suggested to act as the critical regulator in several diseases. This study is designed to investigate the role of circCSNK1G3 on RCC progression. We observed a highly expression of circCSNK1G3 in RCC tissues compared with normal tissues. The aberrantly circCSNK1G3 promoted the tumour growth and metastasis in RCC. In the subsequent mechanism investigation, we discovered that the tumour-promoting effects of circCSNK1G3 were, at least partly, achieved by up-regulating miR-181b. Increased miR-181b inhibits several tumour suppressor gene, including CYLD, LATS2, NDRG2 and TIMP3. Furthermore, the decreased TIMP3 leads to the enhanced epithelial to mesenchymal transition (EMT) process, thus promoting the cancer metastasis. In conclusion, we identified the oncogenic role of circCSNK1G3 in RCC progression and demonstrated the regulatory role of circCSNK1G3 induced miR-181b expression, which leads to TIMP3-mediated EMT process, thus resulting in tumour growth and metastasis in RCC. This study reveals the promise of circCSNK1G3 to be developed as a potential diagnostic and prognostic biomarker in the clinic. And the roles of circCSNK1G3 in cancer research deserve further investigation.

Comprehensive landscape of extracellular vesicle-derived RNAs in cancer initiation, progression, metastasis and cancer immunology.

Extracellular vesicles (EVs), a class of heterogeneous membrane vesicles, are generally divided into exosomes and microvesicles on basis of their origination from the endosomal membrane or the plasma membrane, respectively. EV-mediated bidirectional communication among various cell types supports cancer cell growth and metastasis. EVs derived from different cell types and status have been shown to have distinct RNA profiles, comprising messenger RNAs and non-coding RNAs (ncRNAs). Recently, ncRNAs have attracted great interests in the field of EV-RNA research, and growing numbers of ncRNAs ranging from microRNAs to long ncRNAs have been investigated to reveal their specific functions and underlying mechanisms in the tumor microenvironment and premetastatic niches. Emerging evidence has indicated that EV-RNAs are essential functional cargoes in modulating hallmarks of cancers and in reciprocal crosstalk within tumor cells and between tumor and stromal cells over short and long distance, thereby regulating the initiation, development and progression of cancers. In this review, we discuss current findings regarding EV biogenesis, release and interaction with target cells as well as EV-RNA sorting, and highlight biological roles and molecular mechanisms of EV-ncRNAs in cancer biology.

Emerging landscape of circular RNAs in lung cancer.

Lung cancer, the leading cause of cancer deaths worldwide, is characterized with malignant cell growth. Advances in next-generation sequencing has helped us further understand RNA and identify novel circular RNAs (circRNAs) that may be useful in the early diagnosis and treatment of lung cancer. Similar to other noncoding RNAs, circRNAs present diverse biological functions in normal and disease states, including various types of cancers. This review focuses mainly on the poorly understood functions of circRNA in lung cancer. This paper also summarizes the recent advances in circRNA biogenesis, analyzes the role of circRNAs in cancers, and discusses the potential mechanisms of circRNAs in lung cancer.