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This work aims to study the effects of oral gavage (0.2 mg/g body weight) of elaidic acid (C18:1–9 t, EA) and linoelaidic acid (C18:2–9 t,12 t, LEA) on lipid metabolism, inflammation and gut homeostasis of mice. Results showed that both EA and LEA gavage significantly increased LDL-c, TC and oxidative stress levels in the liver and serum and may stimulate liver inflammation via NF-κB and MAPK signaling pathway. Compared with EA, LEA gavage significantly promoted TAG accumulation and inflammatory signaling. Serum lipidomics revealed that LEA intake significantly increased the concentration of ∼50 TAGs, while EA gavage primarily caused significant decreases in several SMs. 16S rRNA demonstrated that LEA ingestion markedly changed fecal microbiota by enriching Lactobacillus (phylum Firmicutes), however, EA treatment did not affect it. Overall, LEA gavage has more severe consequences on TAG accumulation, inflammation and microbial structure than EA, highlighting that the number of trans double bonds affects these processes.

Background: Hypertension, a highly prevalent chronic disease, is known to inflict severe damage upon blood vessels. In our previous study, isoliensinine, a kind of bibenzyl isoquinoline alkaloid which isolated from a TCM named Lotus Plumule (Nelumbo nucifera Gaertn), exhibits antihypertensive and vascular smooth muscle proliferation-inhibiting effects, but its application is limited due to poor water solubility and low bioavailability. In this study, we proposed to prepare isoliensinine loaded by PEG-PLGA polymer nanoparticles to increase its efficacy Method: We synthesized and thoroughly characterized PEG-PLGA nanoparticles loaded with isoliensinine using a nanoprecipitation method, denoted as, PEG-PLGA@Isoliensinine. Additionally, we conducted comprehensive investigations into the stability of PEG-PLGA@Isoliensinine, in vitro drug release profiles, and in vivo pharmacokinetics. Furthermore, we assessed the antihypertensive efficacy of this nano-system through in vitro experiments on A7R5 cells and in vivo studies using AngII-induced mice. Result: The findings reveal that PEG-PLGA@Isoliensinine significantly improves isoliensinine absorption by A7R5 cells and enhances targeted in vivo distribution. This translates to a more effective reduction of AngII-induced hypertension and vascular smooth muscle proliferation. Conclusion: In this study, we successfully prepared PEG-PLGA@Isoliensinine by nano-precipitation, and we confirmed that PEG-PLGA@Isoliensinine surpasses free isoliensinine in its effectiveness for the treatment of hypertension, as demonstrated through both in vivo and in vitro experiments. Significance: This study lays the foundation for isoliensinine's clinical use in hypertension treatment and vascular lesion protection, offering new insights for enhancing the bioavailability of traditional Chinese medicine components. Importantly, no toxicity was observed, affirming the successful implementation of this innovative drug delivery system in vivo and offers a promising strategy for enhancing the effectiveness of Isoliensinine and propose an innovative avenue for developing novel formulations of traditional Chinese medicine monomers.

Background: Qing Hua Chang Yin (QHCY) is a famous formula of traditional Chinese medicine (TCM) and has been proven to have protective effect on ulcerative colitis. However, its protective effect and potential therapeutic mechanisms in chronic colitis remain unclear. The purpose of this study is to explore the effects and underlying mechanisms of QHCY on dextran sulfate sodium (DSS)-induced chronic colitis mice model.Methods: The chronic colitis model was established by administration of 2% DSS for three consecutive cycles of 7 days with two intervals of 14 days for recovery by drinking water. The experiment lasted 49 days. The DSS + QHCY group received QHCY administration by oral gavage at doses of 1.6 g/kg/d, DSS + Mesalazine group was administrated Mesalazine by oral gavage at doses of 0.2 g/kg/d. The control and DSS group were given equal volume of distilled water. The body weight, stool consistency and blood in stool were monitored every 2 days. The disease activity index (DAI) was calculated. The colon length was measured after the mice were sacrificed. The histomorphology of colonic tissues was checked by the HE and PAS staining. Immunohistochemistry was performed to detect the expressions of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), tight junction proteins (ZO-1, occludin) and Mucin2 (MUC2). 16S rRNA sequencing analysis was conducted to study the diversity and abundance of gut microbiota changes.Results: QHCY treatment not only significantly attenuated DSS-induced the weight loss, DAI score increase, colon shortening and histological damage in mice, but also decreased the expression of pro-inflammatory cytokines in colonic tissues and increased the expression of ZO-1, occludin, and MUC2. Furthermore, QHCY enhanced the diversity of gut microbes and regulated the structure and composition of intestinal microflora in mice with chronic colitis.Conclusion: QHCY has a therapeutic effect on a murine model of chronic colitis. It can effectively reduce the clinical and pathological manifestations of colitis and prevent alterations in the gut microbiota.

Ischemic-reperfusion injury (IRI) is a major pathogenic factor in acute kidney injury (AKI), which directly leads to the hypoxic injury of renal tubular epithelial cells (RTECs). Although emerging studies suggest repressor element 1–silencing transcription factor (REST) as a master regulator of gene repression under hypoxia, its role in AKI remains elusive. Here, we found that REST was upregulated in AKI patients, mice, and RTECs, which was positively associated with the degree of kidney injury, while renal tubule–specific knockout of Rest significantly alleviated AKI and its progression to chronic kidney disease (CKD). Subsequent mechanistic studies indicated that suppression of ferroptosis was responsible for REST-knockdown-induced amelioration of hypoxia-reoxygenation injury, during which process Cre-expressing adenovirus–mediated REST downregulation attenuated ferroptosis through upregulating glutamate-cysteine ligase modifier subunit (GCLM) in primary RTECs. Further, REST transcriptionally repressed GCLM expression via directly binding to its promoter region. In conclusion, our findings revealed the involvement of REST, a hypoxia regulatory factor, in AKI-to-CKD transition and identified the ferroptosis-inducing effect of REST, which may serve as a promising therapeutic target for ameliorating AKI and its progression to CKD.

Abstract The delivery of biomolecules by extracellular vesicles (EVs) derived from endothelial progenitor cells (EPCs) has been proven to ameliorate sepsis, yet the therapeutic mechanism remains to be elucidated. Taurine upregulated gene 1 (TUG1) is a long noncoding RNA (lncRNA) that is downregulated in sepsis. The current study was designed to explore the role of EPCs derived EVs transmitting TUG1 in macrophage polarization and macrophage-mediated inflammation in a cecal ligation and puncture (CLP)-induced sepsis mouse model. TUG1 was underexpressed in CLP-induced sepsis, and its reexpression induced anti-inflammatory macrophage polarization and suppressed macrophage-medicated inflammatory injury to the pulmonary vascular endothelium. EPCs derived EVs transmitted TUG1 to promote M2 macrophage polarization. Luciferase, RIP, and RNA pull-down assays showed that TUG1 could competitively bind to microRNA-9-5p (miR-9-5p) to upregulate the expression of sirtuin 1 (SIRT1). Furthermore, EPCs derived EVs transmitted TUG1 to promote M2 macrophage polarization through the impairment of miR-9-5p-dependent SIRT1 inhibition. Finally, EPCs derived EVs carrying TUG1 were verified to ameliorate sepsis-induced organ damage in the murine model. In summary, EPCs derived EVs transmit TUG1 to attenuate sepsis via macrophage M2 polarization. This study also highlights the proinflammatory mechanism associated with miR-9-5p-mediated inhibition of SIRT1, which contributes to a more comprehensive understanding of the pathogenesis of sepsis.

Abstract Background Colorectal cancer (CRC) is one of the most highly malignant tumors and has a complicated pathogenesis. A preliminary study identified syntrophin beta 1 (SNTB1) as a potential oncogene in CRC. However, the clinical significance, biological function, and underlying mechanisms of SNTB1 in CRC remain largely unknown. Thus, the present study aimed to investigate the role of SNTB1 in CRC. Methods The expression profile of SNTB1 in CRC samples was evaluated by database analysis, cDNA array, tissue microarray, quantitative real-time PCR (qPCR), and immunohistochemistry. SNTB1 expression in human CRC cells was silenced using short hairpin RNAs (shRNA)/small interfering RNAs (siRNA) and its mRNA and protein levels were assessed by qPCR and/or western blotting. Cell viability, survival, cell cycle, and apoptosis were determined by the CCK-8 assay, colony formation, and flow cytometry assays, respectively. A xenograft nude mouse model of CRC was established to validate the roles of SNTB1 in vivo. Immunohistochemistry and TUNEL staining were used to determine the expression of SNTB1, PCNA, and cell apoptosis in tissue samples. Isobaric tag for relative and absolute quantification (iTRAQ) was used to analyze the differentially expressed proteins after knockdown of SNTB1 in CRC cells. Silence of protein kinase N2 (PKN2) using si-PNK2 was performed for rescue experiments. Results SNTB1 expression was increased in CRC tissues compared with adjacent noncancerous tissues and the increased SNTB1 expression was associated with shorter overall survival of CRC patients. Silencing of SNTB1 suppressed cell viability and survival, induced cell cycle arrest and apoptosis in vitro, and inhibited the growth of CRC cells in vivo. Further elucidation of the regulation of STNB1 on CRC growth by iTRAQ analysis identified 210 up-regulated and 55 down-regulated proteins in CRC cells after SNTB knockdown. A PPI network analysis identified PKN2 as a hub protein and was up-regulated in CRC cells after SNTB1 knockdown. Western-blot analysis further confirmed that SNTB1 knockdown significantly up-regulated PKN2 protein expression in CRC cells and decreased the phosphorylation of both ERK1/2 and AKT. Moreover, rescue experiments indicated that PKN2 knockdown significantly rescued SNTB1 knockdown-mediated decrease in cell viability, survival, and increase of cell cycle arrest at G0/G1 phase and apoptosis of CRC cells. Conclusions These findings indicate that SNTB1 is overexpressed in CRC. Elevated SNTB1 levels are correlated with shorter patient survival. Importantly, SNTB1 promotes tumor growth and progression of CRC, possibly by reducing the expression of PKN2 and activating the ERK and AKT signaling pathway. Our study highlights the potential of SNTB1 as a new prognostic factor and therapeutic target for CRC.

ObjectiveReports on negative results of metagenomic next-generation sequencing (mNGS) are scarce. We aimed to explore the diagnostic value of negative results in bronchoalveolar lavage fluid (BALF) mNGS and how to deal with the negative results in patients with severe respiratory disease.MethodsA retrospective analysis was performed on patients suspected severe community-acquired pneumonia who were admitted to the respiratory intensive care unit of the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2021. According to the final diagnosis as the reference standard, the negative results of mNGS were divided into a true negative group and a false negative group. For enrolled patients, we recorded their demographic data, imaging results, laboratory results, therapeutic processes, and prognoses.ResultsA total of 21 patients were enrolled in this study, including 16 true negative patients and 5 false negative patients. In the true negative group, interstitial lung diseases were the most and neoplastic diseases were following. In addition to mNGS, 9 patients underwent pathological examination, 7 patients were finally diagnosed by medical history, autoantibodies, and point-of-care (POC) ultrasound. 14 patients eventually discontinued antibiotics, 2 patients underwent antibiotic de-escalation, the average interval time of treatment adjustment was 3.56 ± 2.00 days. In the false negative group, the leading missed pathogen was fungi, followed by tuberculosis bacilli. In contrast to 2 patients underwent pathological examination, 3 patients were confirmed by routine microbiological tests.ConclusionsNegative results of BALF mNGS can help to rule out infection, but missed diagnoses may also exist. It should be re-evaluated with other clinical informations. Pathological examination or repeated mNGS may be viable options when the diagnosis cannot be confirmed.

Cardiorenal syndrome (CRS) is defined as a disorder of the heart and kidney, in which acute or chronic injury of one organ may lead to acute or chronic dysfunction of the other. It is characterized by high morbidity and mortality, resulting in high economic costs and social burdens. However, there is currently no effective drug-based treatment. Emerging evidence implicates the involvement of mitophagy in the progression of CRS, including cardiovascular disease (CVD) and chronic kidney disease (CKD). In this review, we summarized the crucial roles and molecular mechanisms of mitophagy in the pathophysiology of CRS. It has been reported that mitophagy impairment contributes to a vicious loop between CKD and CVD, which ultimately accelerates the progression of CRS. Further, recent studies revealed that targeting mitophagy may serve as a promising therapeutic approach for CRS, including clinical drugs, stem cells and small molecule agents. Therefore, studies focusing on mitophagy may benefit for expanding innovative basic research, clinical trials, and therapeutic strategies for CRS.

Background: Acute kidney injury (AKI) occurs in approximately 7–18% of all hospitalizations, but there are currently no effective drug therapy for preventing AKI or delaying its progression to chronic kidney disease (CKD). Recent studies have shown that Scutellaria baicalensis, a traditional Chinese herb, could attenuate cisplatin-induced AKI, although the mechanism remains elusive. Further, it is unknown whether its major active component, Oroxylin A (OA), can alleviate kidney injury.Methods: The therapeutic effect of OA was evaluated by using ischemia-reperfusion (IR) and cisplatin mediated-AKI mice and HK-2 cells under hypoxia-reoxygenation (HR) conditions. HE staining, transmission electron microscopy, flow cytometry, immunofluorescence, qPCR, Western blot, PPARα inhibitor, BNIP3 siRNA and ChIP assay were used to explore the role and mechanism of OA in AKI.Results: OA ameliorated tubular damage and dramatically decreased serum creatinine (Scr) and urea nitrogen (BUN), and the expressions of renal injury markers (Kim-1, Ngal) in AKI mice induced by both IR injury and cisplatin, as well as attenuating AKI-to-CKD transition. In vitro experiments showed that OA alleviated HR-induced mitochondrial homeostasis imbalance in renal tubular epithelial cells. Mechanistically, OA dose-dependently induced the expression of Bcl-2/adenovirus E1B 19-kDa interacting protein (BNIP3), while knockdown of BNIP3 expression reversed the protection of OA against HR-mediated mitochondrial injury. Network pharmacological analysis and experimental validation suggested that OA enhanced BNIP3 expression via upregulating the expression of peroxisome proliferator activated receptor alpha (PPARα), which induced the transcription of BNIP3 via directly binding to its promoter region. Both in vitro and in vivo experiments confirmed that the renoprotective effect of OA was dramatically reduced by GW6471, a PPARα antagonist.Conclusion: Our findings revealed that OA ameliorates AKI-to-CKD transition by maintaining mitochondrial homeostasis through inducing PPARα-BNIP3 signaling pathway, indicating that OA may serve as a candidate therapeutic strategy for alleviating AKI and CKD.

The etiology of acute lung injury (ALI) is not clear, and the treatment of ALI presents a great challenge. This study aimed to investigate the pathogenesis and potential therapeutic targets of ALI and to define the target gene of Tanreqing (TRQ), which is a traditional Chinese medicine formula composed of five medicines, scutellaria baicalensis, bear bile powder, goat horn powder, honeysuckle and forsythia. Macrophage activation plays a critical role in many pathophysiological processes, such as inflammation. Although the regulation of macrophage activation has been extensively investigated, there is little knowledge of the role of long noncoding RNAs (lncRNAs) in this process. In this study, we found that lncRNA-SNHG1 expression is distinctly regulated in differently activated macrophages in that it is upregulated in LPS. LncRNA-SNHG1 knockdown attenuates LPS-induced M1 macrophage activation. The SNHG1 promoter was bound by NF-κB subunit p65, indicative of SNHG1 being a direct transcriptional target of LPS-induced NF-κB activation. SNHG1 acts as a proinflammatory driver that leads to the production of inflammatory cytokines and the activation of macrophages and cytokine storms by physically interacting with high-mobility group box 1 (HMGB1) in ALI. TRQ inhibited NF-κB signaling activation and binding of NF-κB to the SNHG1 promoter. In conclusion, this study defined TRQ target genes, which can be further elucidated as mechanism(s) of TRQ action, and provides insight into the molecular pathogenesis of ALI. The lncRNA-SNHG1/HMGB1 axis is an ideal therapeutic for ALI treatment.

Using the products of European Centre for Medium-range Weather Forecasts (ECMWF) ensemble prediction and rain gauge data with interval of 6 hours from July 1 to August12 in 2019, we have established a precipitation probability forecast model (hereinafter referred to as the BMA model) based on Bayesian Model Average, and then conducted a comparative analysis of the deterministic forecast and probability forecast of typhoon Lekima precipitation based on the BMA model with respect to the raw ensemble forecast of ECMWF. The main results are as follow. (1) In general, the BMA model has a good correction to the typhoon precipitation ensemble prediction, and it can improve the dispersion of ensemble prediction effectively. (2) Compared with the raw ensemble forecast, the averaged values of CRPS, MAE and RMSE of the BMA model were reduced by 13%, 34% and 25%, respectively, which improved the reliability of the forecast to some extent. However, the improvement degree gradually weakened as the precipitation grade increased. The BMA model can also reduce the false alarm of probability prediction of rainstorm and heavier precipitation to a certain extent. It can also improve the accuracy of typhoon Lekima rainstorm and heavier precipitation' s area forecast. (3) In this case, the 25th percentile to the 95th percentile forecast can be regarded as an effective prediction interval. The effective prediction interval revised by the BMA model has a stronger ability to capture precipitation observations, and the ensemble forecast capture rate revised by the BMA model is 13.3% higher than that of raw ensemble forecast.

The incidence of non-HIV-infected Pneumocystis Jirovecii Pneumonia (PJP) is increasing. The prognosis for non-HIV PJP is poor and diagnostic tests are of lower sensitivity in non-HIV patients. Metagenomic next-generation sequencing (mNGS) was compared with routine detection assays, including Gomori methenamine silver (GMS) stain and polymerase chain reaction (PCR) technique. Specimens of 4 bronchoalveolar lavages (BAL) and 1 lung tissue samples were obtained from 4 non-HIV patients from our hospitals. Although both GMS and mNGS were positive for P. jirovecii with PCR as positive control, the testing time of mNGS was obviously shorter than GMS. Compared with the traditional GMS method, mNGS has absolute advantages. However, the issue with PJP presentations having atypical symptoms and ambiguous imaging features persists. Hence, the disease can easily be ignored. Secondly, PJP progresses rapidly in non-HIV-infected patients and can cause severe respiratory failure with unfavorable prognosis. This study affirms that mNGS can be used to quickly and accurately diagnose PJP, but a combination of clinical judgement of symptoms, laboratory testing, and imaging examination is required to make a comprehensive judgment along with mNGS test results.

Emerging evidences demonstrate the involvement of gut microbiota in the progression of chronic kidney disease (CKD) and CKD-associated complications including cardiovascular disease (CVD) and intestinal dysfunction. In this review, we discuss the interactions between the gut, kidney and heart in CKD state, and elucidate the significant role of intestinal microbiota in the gut-kidney-heart axis hypothesis for the pathophysiological mechanisms of these diseases, during which process mitochondria may serve as a potential therapeutic target. Dysregulation of this axis will lead to a vicious circle, contributing to CKD progression. Recent studies suggest novel therapies targeting gut microbiota in the gut-kidney-heart axis, including dietary intervention, probiotics, prebiotics, genetically engineered bacteria, fecal microbiota transplantation, bacterial metabolites modulation, antibiotics, conventional drugs and traditional Chinese medicine. Further, the identification of specific microbial communities and their corresponding pathophysiological metabolites and the illumination of the gut-kidney-heart axis may contribute to innovative basic research, clinical trials and therapeutic strategies against CKD progression and uremic complications in CKD patients.

Acute respiratory distress syndrome (ARDS) is a high-mortality disease and lacks effective pharmacotherapy. A traditional Chinese medicine (TCM) formula, Ning Fei Ping Xue (NFPX) decoction, was demonstrated to play a critical role in alleviating inflammatory responses of the lung. However, its therapeutic effectiveness in ARDS and active compounds, targets, and molecular mechanisms remain to be elucidated. The present study investigates the effects of NFPX decoction on ARDS mice induced by lipopolysaccharides (LPS). The results revealed that NFPX alleviated lung edema evaluated by lung ultrasound, decreased lung wet/Dry ratio, the total cell numbers of bronchoalveolar lavage fluid (BALF), and IL-1β, IL-6, and TNF-α levels in BALF and serum, and ameliorated lung pathology in a dose-dependent manner. Subsequently, UPLC-HRMS was performed to establish the compounds of NFPX. A total of 150 compounds in NFPX were characterized. Moreover, integrating network pharmacology approach and transcriptional profiling of lung tissues were performed to predict the underlying mechanism. 37 active components and 77 targets were screened out, and a herbs-compounds-targets network was constructed. Differentially expressed genes (DEGs) were identified from LPS-treated mice compared with LPS combined with NFPX mice. GO, KEGG, and artificial intelligence analysis indicated that NFPX might act on various drug targets. At last, potential targets, HRAS, SMAD4, and AMPK, were validated by qRT-PCR in ARDS murine model. In conclusion, we prove the efficacy of NFPX decoction in the treatment of ARDS. Furthermore, integrating network pharmacology, transcriptome, and artificial intelligence analysis contributes to illustrating the molecular mechanism of NFPX decoction on ARDS.

Background: Influenza virus is a common pathogen causing community-acquired pneumonia. After H1N1 infection, some patients present with rapid disease progression and various respiratory complications, especially immunocompromised patients and pregnant women. However, most patients have a favorable prognosis. Influenza viruses infect respiratory epithelial cells, leading to diffuse alveolar damage (DAD), which could induce secondary bacterial or fungal infections that could lead to serious complications, such as acute respiratory failure, severe pneumonia, pneumothorax, mediastinal emphysema, acute respiratory distress syndrome (ARDS) and post-ARDS fibrosis.Objective: The short-term mortality rate of ARDS is decreasing, and understanding survivors’ posthospitalization outcomes is very important. Our aim was to evaluate the outcomes of 69 patients who survived H1N1 pneumonia with severe respiratory complications and abnormal CT findings and developed post-ARDS pulmonary fibrosis.Materials and methods: The 280 inpatients included in this trial had been diagnosed with H1N1 infection that was confirmed by pharyngeal sputum or swab tests. The data were collected from January 2018 to January 2020 in the First Affiliated Hospital of Zhengzhou University and the Sixth People's Hospital of Zhengzhou. Of these patients, 232 had CT findings indicating pulmonary fibrosis after H1N1 infection, and 69 survived and consented to participate in this study. 6°months after diagnosis, the 69 surviving patients were interviewed and underwent physical examinations, CT scans, 6°min walk tests, and quality-of-life evaluations (SF-36). We analyzed the baseline variables and six-month outcomes of post-ARDS pulmonary fibrosis in patients with H1N1 pneumonia.Results: Of the 69 surviving patients with post-ARDS pulmonary fibrosis, there were 24 females and 45 males, with a mean age of 53.7 ± 16.8°years; 18 patients (26%) had no underlying disease, and 14 (20%) patients had more than one underlying disease. The distance walked in 6°min increased from an average of 451.9°m at 3°months to 575.4°m at 6°months; the mean 36-Item Short Form Survey (SF-36) physical function score increased from an average of 75.3 at 3°months to 77.5 at 6°months; and the average CT score decreased from 31.3 at 3°months to 14.8 at 6°months. Treatment with systemic corticosteroids and the presence of an underlying disease were related to the CT score and the distance walked in 6°min.Conclusion: Among the survivors with pulmonary fibrosis after H1N1 influenza, the 6°min walk test and CT scores continued to be affected after 6°months. The 6°min walk distance and imaging findings improved during the first 6°months. The health-related QoL (HRQoL) scores of H1N1 pneumonia survivors were lower than those of sex- and age-matched controls.

Long non-coding RNAs (lncRNAs) small nucleolar RNA host gene 14 (SNHG14) has been identified as an oncogene involved in the progression of various human cancers. Nevertheless, the functional role and molecular mechanism of SNHG14 on NSCLC remain largely elusive. qRT-PCR assay was performed to detect the levels of SNHG14, miR-34a and high mobility group box 1 (HMGB1) mRNA. HMGB1 protein level was assessed by western blot analysis. CCK-8 assay was used to determine the IC50 value of cisplatin (CDDP), and transwell assays were employed to detect cell migration and invasion abilities. Cell apoptosis was determined by flow cytometric analysis. Dual-luciferase reporter assay, RNA immuoprecipitation assay and RNA pull-down assay were performed to confirm the interaction between SNHG14 and miR-34a, or miR-34a and HMGB1. Our data demonstrated that SNHG14 was upregulated in NSCLC cells, and SNHG14 silencing repressed the migration, invasion while accelerated the apoptosis of NSCLC cells. Moreover, we manifested that SNHG14 silencing promoted NSCLC cell sensitivity to CDDP. SNHG14 repressed miR-34a expression by binding to miR-34a. Additionally, SNHG14 regulated HMGB1 expression by sponging miR-34a. SNHG14 silencing exerted its regulatory effect by miR-34a and HMGB1 mediated the regulatory effect of miR-34a on NSCLC cells. In conclusion, SNHG14 silencing suppressed NSCLC progression at least partly by miR-34a/HMGB1 axis in vitroand promoted NSCLC cell sensitivity to CDDP, highlighting that SNHG14 might be a potential target for NSCLC therapy.

Lung alveolar epithelial cells are exposed to hypoxia under a variety of physiological and pathological conditions. It has been shown recently that miR-143, which can directly target the key glycolytic enzyme hexokinase II (HK2), may be regulated by miR-155. We investigated whether microRNAs contribute to the cellular glycolysis in response to hypoxia. Using the A549 cells, we found that the expression of Dicer is decreased under hypoxia. When Dicer was knocked down with small-interfering RNA (siRNA), pre-miR143 was increased and mature miR-143 was decreased as that in hypoxia, indicating that reduction of Dicer is responsible for the change of miR-143 under hypoxia. Interestingly, both hypoxia and knockdown of Dicer resulted in miR-155 and pre-miR-155 expression increases. We also examined the expression of HK2 and glucose metabolism in the cells. Both HK2 mRNA and protein were increased under hypoxia, which is accompanied by an increase of glucose uptake and production of lactate. The same alterations were found with siRNA Dicer knockdown. More-over, transfection with anti-miR-143 also led to a HK2 production and an increase of glucose uptake and lactate production, whereas anti-miR-155 had opposite effects. The miR-143 and anti-miR-155 transfection resulted in a significant cell apoptosis. The expression of Dicer was decreased with HK2 accumulating in mouse lung tissues under hypoxia identified by immunohistochemistry. The changes of miR-143 and miR-155 were similar to those in A549 cells. Our data demonstrate that Dicer regulation of miRNAs promotes HK2 activation and glycolysis, which might protect the cell from hypoxic damage and enter into an adaptive process. [ABSTRACT FROM AUTHOR]