Clinical analysis of infectious endophthalmitis following glaucoma filtration surgery.

BACKGROUND: This study aimed to evaluate the clinical correlative factors and outcomes of treatment of bleb-associated endophthalmitis (BAE) following glaucoma filtration surgery in a Chinese population from the year 2012 to 2022, and to compare them with the clinical course during the coronavirus disease (COVID-19) pandemic period. METHODS: This was a retrospective analysis of consecutive cases of BAE treated at the Eye & ENT Hospital of Fudan University, Shanghai, China, between January 1, 2012, and December 31, 2022. The clinical presentation, treatment modality, microbiological data, clinical course, and outcomes of visual acuity (VA) and intraocular pressure (IOP) in all BAE cases were collected and analyzed. RESULTS: A total of 28 eyes with BAE were examined, predominantly in male patients (71.4%, p = 0.023). Most patients underwent trabeculectomy (89.3%, p ≤ 0.001), while a smaller proportion underwent Ex-PRESS implantation (10.7%). Primary open-angle glaucoma (POAG) was the most common type of glaucoma (39.3%, p ≤ 0.001). Most patients (96.4%) presented with poor visual acuity, worse than 20/400, and IOP ranged from 3-60 mmHg. Treatment, including initial tap-and-inject procedure of antibiotics (Ceftazidime and Norvancomycin) or initial pars plana vitrectomy (PPV), was initiated 5.0 ± 7.1 days after BAE onset. Streptococcus was the most common causative organism (53.6% of cases, p ≤ 0.001). The visual acuity significantly improved from 2.58 ± 0.27 to 2.14 ± 0.85 (reported in logMAR) after treatment (p ≤ 0.001), and most patients maintained normal tension during follow-up. Poisson regression model analysis showed the annual incidence of BAE during the COVID-19 pandemic period was significantly twice greater than that of previous years. CONCLUSIONS: BAE may cause irreversible visual impairment. POAG filtering surgery with male sex and the COVID-19 pandemic period might be potentially relevant factors for BAE. Culture positivity was closely related to BAE prognosis, with Streptococcus species being the leading pathogenic organisms. Online outpatient services, early diagnosis, and timely treatment may rescue vision and maintain IOP control in the presence of BAE.

National survey on the availability of oncology palliative care services at tertiary general and cancer hospitals in China.

BACKGROUND: This nationwide survey studied the level of palliative care (PC) access for Chinese patients with cancer among cancer care providers either in tertiary general hospitals or cancer hospitals in China. METHODS: Using a probability-proportionate-to-size method, we identified local tertiary general hospitals with oncology departments to match cancer hospitals at the same geographic area. A PC program leader or a designee at each hospital reported available PC services, including staffing, inpatient and outpatient services, education, and research, with most questions adapted from a previous national survey on PC. The primary outcome was availability of a PC service. RESULTS: Most responders reported that some type of PC service (possibly called "comprehensive cancer care," "pain and symptom management," or "supportive care") was available at their institution (84.3% of tertiary general hospitals, 82.8% of cancer hospitals). However, cancer hospitals were significantly more likely than tertiary general hospitals to have a PC department or specialist (34.1% vs. 15.5%, p < 0.001). The most popular services were pain consultation (> 92%), symptom management (> 77%), comprehensive care plans (~ 60%), obtaining advanced directives and do-not-resuscitate orders (~ 45%), referrals to hospice (> 32%), and psychiatric assessment (> 25%). Cancer hospitals were also more likely than tertiary general hospitals to report having inpatient beds for PC (46.3% vs. 30.5%; p = 0.010), outpatient PC clinics (28.0% vs. 16.8%; p = 0.029), educational programs (18.2% vs. 9.0%, p = 0.014), and research programs (17.2% vs. 9.3%, p < 0.001). CONCLUSIONS: Cancer hospitals are more likely to offer PC than are tertiary general hospitals in China. Our findings highlight opportunities to further increase the PC capacity in Chinese hospitals.

Low-cost Zinc-Iron Flow Batteries for Long-Term and Large-Scale Energy Storage.

Aqueous flow batteries are considered very suitable for large-scale energy storage due to their high safety, long cycle life, and independent design of power and capacity. Especially, zinc-iron flow batteries have significant advantages such as low price, non-toxicity, and stability compared with other aqueous flow batteries. Significant technological progress has been made in zinc-iron flow batteries in recent years. Numerous energy storage power stations have been built worldwide using zinc-iron flow battery technology. This review first introduces the developing history. Then, we summarize the critical problems and the recent development of zinc-iron flow batteries from electrode materials and structures, membranes manufacture, electrolyte modification, and stack and system application. Finally, we forecast the development direction of the zinc-iron flow battery technology for large-scale energy storage.

RAB6A functions as a critical modulator of the stem-like subsets in cholangiocarcinoma.

RAB6A is a member of RAB GTPase family and plays an important role in the targeted transport of neurotrophic receptors and inflammatory cytokines. RAB6A-mediated secretory pathway is involved in many physiological and pathological processes. Defects in RAB6A-mediated secretory pathway may lead to the development of many diseases, including cancer. However, its role in cholangiocarcinoma (CCA) has not yet been revealed. We explored the regulatory role of RAB6A in the stem-like subsets of CCA. We showed that RAB6A knockdown (KD) impedes cancer stem cells (CSCs) properties and epithelial-mesenchymal transition in vitro and that suppression of RAB6A inhibits tumor growth in vivo. We screened target cargos of RAB6A in CCA cells and identified a extracellular matrix component as the target cargo. RAB6A binds directly to OPN, and RAB6A KD suppressed OPN secretion and inhibited the interaction between OPN and αV integrin receptor. Moreover, RAB6A KD inhibited the AKT signaling pathway, which is a downstream effector of the integrin receptor signaling. In addition, shRNA targeting OPN blocked endogenous expression of OPN and consequently weakened CSCs properties in RAB6A-formed spheres. Similarly, inhibitor of AKT signaling, MK2206 also impedes oncogenic function of RAB6A in the stem-like subsets of CCA cells. In conclusion, our findings showed that RAB6A sustains CSCs phenotype maintenance by modulating the secretion of OPN and consequentially activating the downstream AKT signaling pathway. Targeting the RAB6A/OPN axis may be an effective strategy for CCA therapy.

Publication trends of primary angle-closure disease during 1991-2022: a bibliometric analysis.

AIM: To perform a bibliometric analysis in the field of primary angle-closure disease (PACD) research to characterize current global trends and compare contributions from different countries, institutions, journals, and authors. METHODS: All PACD-related publications from 1991 to 2022 from the Web of Science Core Collection database were extracted. Microsoft Excel and VOSviewer were used to collect publication data, analyze publication trends, and visualize relevant results. RESULTS: A total of 1721 publications with 34 591 citations were identified. China produced the most publications (554) while ranking third in citations (8220 times). The United States contributed the most citations (12 315 times) with publications (362) ranking second. The Investigative Ophthalmology Visual Science was the most productive journal concerning PACD, and Aung Tin was the author with the highest number of publications in the field. Keywords were classified into three clusters, epidemiology and pathogenesis research, optical coherence tomography (OCT) and other imaging examinations, and glaucoma surgery treatment. Genome-wide association, susceptibility loci, OCT, and combined phacoemulsification have become new hot research topics in recent years since 2015. CONCLUSION: China, the United States, and Singapore make the most outstanding contributions in the field of PACD research. OCT, combined phacoemulsification, and gene mutation-related study, are considered the potential focus for future research.

FBXO31 sensitizes cancer stem cells-like cells to cisplatin by promoting ferroptosis and facilitating proteasomal degradation of GPX4 in cholangiocarcinoma.

BACKGROUND & AIMS: Cholangiocarcinoma (CCA) is a malignant tumour originating from the biliary epithelium that easily infiltrates, metastasizes and recurs. The deficiency of FBXO31 facilitates the initiation and progression of several types of cancer. However, the involvement of FBXO31 in CCA progression has remained unclear. METHODS: qRT-PCR was used to detect the expression of FBXO31 in CCA. The biological functions of FBXO31 were confirmed in vivo and in vitro. Sphere formation and flow cytometry were used to identify the stem cell properties of CCA. RESULTS: FBXO31 is downregulated in CCA and that deficiency of FBXO31 is associated with the TNM stage of CCA. Functional studies showed FBXO31 inhibits cell growth, migration, invasion, cancer stem cell (CSC) properties and epithelial-mesenchymal transition (EMT) in vitro and impedes tumour growth in vivo. In addition, overexpression of FBXO31 increases the cisplatin (CDDP) sensitivity of CCA cells. RNA-sequencing analysis revealed that FBXO31 is involved in redox biology and metal ion metabolism in CCA cells during CDDP treatment. Further studies revealed that FBXO31 enhances ferroptosis induced by CDDP in CCA and CSC-like cells. FBXO31 enhances ubiquitination of glutathione peroxidase 4 (GPX4), which leads to proteasomal degradation of GPX4. Moreover, overexpression of GPX4 compromises the promoting effects of FBXO31 on CDDP-induced ferroptosis in CCA and CSC-like cells. CONCLUSIONS: Our studies indicate that FBXO31 functions as a tumour suppressor in CCA and sensitizes CSC-like cells to CDDP by promoting ferroptosis and facilitating the proteasomal degradation of GPX4.

RAB37 Promotes Adipogenic Differentiation of hADSCs via the TIMP1/CD63/Integrin Signaling Pathway.

The adipogenic differentiation ability of human adipose-derived mesenchymal stem cells (hADSCs) is critical for the construction of tissue engineering adipose, which shows promising applications in plastic surgery and regenerative medicine. RAB37 is a member of the small RabGTPase family and plays a critical role in vesicle trafficking. However, the role of RAB37 in adipogenic differentiation of hADSCs remains unclear. Here, we report that both the mRNA and protein levels of RAB37 fluctuated during adipogenic differentiation. Upregulation of RAB37 was observed at the early stage of adipogenic differentiation, which was accompanied by increased expression of transcription factors PPARγ2 and C/EBPα, and lipoprotein lipase (LPL). Overexpression of RAB37 promoted adipogenesis of hADSCs, as revealed by Oil Red O staining and increased expression of PPARγ2, C/EBPα, and LPL. Several upregulated cytokines related to RAB37-mediated adipogenic differentiation were identified using a cytokine array, including tissue inhibitor of matrix metalloproteinase 1 (TIMP1). ELISA confirmed that upregulation of RAB37 increased the secretion of TIMP1 by hADSCs. Proximity ligation assay showed that RAB37 interacts with TIMP1 directly. Knockdown of TIMP1 compromised RAB37-mediated adipogenic differentiation. In addition, TIMP1 binds membrane receptor CD63 and integrin ß1. RAB37 promotes Tyr397 phosphorylation of FAK, an important protein kinase of the integrin ß1 signaling. Moreover, both knockdown of CD63 and inhibitor of FAK impeded RAB37-mediated adipogenic differentiation. In conclusion, RAB37 positively regulates adipogenic differentiation of hADSCs via the TIMP1/CD63/integrin ß1 signaling pathway.

FBXO31 modulates activation of hepatic stellate cells and liver fibrogenesis by promoting ubiquitination of Smad7.

Liver fibrosis is a critical pathological process in the early stage of many liver diseases, including hepatic cirrhosis and liver cancer. However, the molecular mechanism is not fully revealed. In this study, we investigated the role of F-box protein 31 (FBXO31) in liver fibrosis. We found FBXO31 upregulated in carbon tetrachloride (CCl4 ) induced liver fibrosis and in activated hepatic stellate cells, induced by transforming growth factor-ß (TGF-ß). The enforced expression of FBXO31 caused enhanced proliferation and increased expression of α-smooth muscle actin (α-SMA) and Col-1 in HSC-T6 cells. Conversely, suppression of FBXO31 resulted in inhibition of proliferation and decreased accumulation of α-SMA and Col-1 in HSC-T6 cells. In addition, upregulation of FBXO31 in HSC-T6 cells decreased accumulation of Smad7, the negative regulator of the TGF-ß/smad signaling pathway, and suppression of the FBXO31 increased accumulation of Smad7. Immunofluorescence staining showed FBXO31 colocalized with Smad7 in HSC-T6 cells and in liver tissues of BALB/c mice treated with CCl4 . Immunoprecipitation demonstrated FBXO31 interacted with Smad7. Moreover, FBXO31 enhanced ubiquitination of Smad7. In conclusion, FBXO31 modulates activation of HSCs and liver fibrogenesis by promoting ubiquitination of Smad7.

Hepatocellular carcinoma treated with anti-epidermal growth factor receptor antibody nimotuzumab: A case report.

RATIONALE: Molecular targeted therapy provides new ideas and hope for the treatment of hepatocellular cancer. Epidermal growth factor receptor (EGFR) is closely related to tumor cell proliferation, apoptosis, invasion, and metastasis. PATIENT CONCERNS: Several reports indicate that the EGFR is expressed frequently in hepatocellular carcinoma (HCC), thus targeting EGFR research has become a hot topic to explore the treatment of HCC patient. DIAGNOSES: Anti-EGFR might serve as a potential therapeutic agent, especially for patients with HCC who are unable to tolerate chemotherapy and surgery. INTERVENTIONS: Although phase II open-label study of cetuximab in unresectable HCC was negative, the clinical relevance of this report by Song et al which is based on a single patient is questionable. OUTCOMES: We for the first time report that nimotuzumab (an anti-EGFR mAb) resulted in a complete remission (CR) in an 87-year-old patient with HCC. The patient was in B stage according to Barcelona center staging criteria and his liver function was Child-Pugh B grade. LESSONS: Our case suggested that anti-EGFR mAbs might be potential therapeutic options for HCC.

MiR-4673 Modulates Paclitaxel-Induced Oxidative Stress and Loss of Mitochondrial Membrane Potential by Targeting 8-Oxoguanine-DNA Glycosylase-1.

BACKGROUND: Our previous study identified a novel microRNA, miR-4673, which is upregulated in A549 cells exposed to paclitaxel (PTX). In this study, we investigated the role of miR-4673 in PTX-induced cytotoxicity. METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, apoptosis assay, 5,5',6,6'-Tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide (JC-1) staining and 2',7'-Dichlorofluorescein (DCFH) staining were used to evaluate cell viability, apoptosis, mitochondrial membrane potential (MMP) loss and reactive oxygen species (ROS) generation in A549 and H1299 cells. Bioinformatics analysis and Luciferase reporter assay were used to explore whether 8-oxoguanine-DNA glycosylase-1 (OGG1) is a target gene of miR-4673. RESULTS: Enforced expression of miR-4673 decreased cell viability and increased PTX-induced apoptosis, MMP loss and reactive oxygen species (ROS) generation in A549 and H1299 cells. Bioinformatics analysis, which was used to identify potential target of miR-4673, revealed a binding site of miR-4673 in 3'UTR of OGG1. Luciferase reporters assays showed that miR-4673 specifically binds to 'CUGUUGA' in 3'UTR of OGG1. Enforced expression of miR-4673 decreased accumulation of OGG1. In addition, silencing OGG1 enhanced inhibitory effects of PTX on apoptosis, MMP loss and ROS generation, which is similar to effects of miR-4673. Moreover, enforced expression of OGG1 compromised promoting effects of miR-4673 on PTX-induced apoptosis, MMP loss and ROS generation. CONCLUSION: miR-4673 modulates PTX-induced apoptosis, MMP loss and ROS generation by targeting OGG1.

miR-363-3p inhibits tumor growth by targeting PCNA in lung adenocarcinoma.

Increasing evidence suggests that microRNAs play key roles in lung cancer. Our previous study demonstrated that microRNA 363-3p (miR-363-3p) is downregulated in lung cancer tissues. In this study, we demonstrated that overexpression of miR-363-3p inhibits the proliferation and colony formation of A549 and H441 cells, while silencing of miR-363-3p has the converse effects. The anti-oncogenic function of miR-363-3p was verified in a mouse tumor xenograft model. Furthermore, cell cycle analysis showed miR-363-3p can induce S phase arrest by downregulating Cyclin-D1 and upregulating Cyclin-dependent kinase-2 in lung adenocarcinoma cells. Additionally, miR-363-3p enhances cell apoptosis, whereas miR-363-3p inhibitor prevents apoptosis and leads to downregulation of Bax and Bak expression. The anti-proliferative function of miR-363-3p toward lung cancer cells may be explained by its ability to inhibit the activation of the mTOR and ERK signaling pathways. Using target prediction software and luciferase reporter assays, we identified PCNA as a specific target of miR-363-3p. miR-363-3p can decreased the accumulation of endogenous PCNA in lung adenocarcinoma cells. Moreover, exogenous expression of PCNA relieve the inhibition of miR-363-3p on cell proliferation, colony formation and mTOR and ERK signaling pathways. Taken together, our data indicate that miR-363-3p suppresses tumor growth by targeting PCNA in lung adenocarcinoma.

Role of deregulated microRNAs in non-small cell lung cancer progression using fresh-frozen and formalin-fixed, paraffin-embedded samples.

Non-small cell lung cancer (NSCLC) is responsible for the highest number of cancer-associated mortalities worldwide, and the five-year survival rate is <15% following the initial diagnosis. MicroRNAs (miRNAs) serve important functions in a number of human diseases, including cancer. The present study investigated the expression status, clinical relevance and functional role of miRNA in NSCLC. miRNA expression profiling was performed in lung adenocarcinoma and adjacent unaffected lung tissues using 47 groups of fresh-frozen (FF) and 45 of formalin-fixed, paraffin-embedded (FFPE) samples from 11 pulmonary bulla. miR-21, -30e, -363 and -623 were further examined for differential expression in two independent cohorts. Other miRNAs, including miR-5100 and miR-650, were upregulated, while miR-10a and -26b were downregulated in FF NSCLC tissues. The associations between these miRNAs and their clinicopathological features were also investigated. miR-363, -10a and -145 were associated with lymph node status (P=0.002, 0.005 and 0.007, respectively) and miR-650 and -145 were associated with differentiation (P=0.01 and 0.05, respectively). No associations were identified for the other miRNAs examined. In the FFPE NSCLC samples, miR-30e-5p correlated with the differentiation of the tissue (P=0.011). The present study indicates that these miRNAs may be appropriate candidates for molecular diagnostic and prognostic markers in NSCLC.

microRNA-506 regulates proliferation, migration and invasion in hepatocellular carcinoma by targeting F-spondin 1 (SPON1).

Our previous study indicates microRNA-506 (miR-506) is downregulated in hepatocellular carcinoma (HCC). In the current study, we investigate the effects of miR-506 on proliferation, migration and invasion in HCC. We report that enforced expression of miR-506 inhibits proliferation, migration and invasion in vitro, and suppresses tumor growth in vivo. Conversely, suppression of miR-506 exhibits promoting effects on proliferation, migration and invasion in vitro, and on tumor growth in vivo. In addition, miR-506 binds to the 3'UTR of F-spondin 1(SPON1), and enforced expression of miR-506 decreases accumulation of SPON1. Moreover, enforced expression of SPON1 and suppression of SPON1 alleviates effects of miR-506 mimics and inhibitors on proliferation, migration and invasion in vitro, respectively. In conclusion, microRNA-506 regulates proliferation, migration and invasion in HCC by targeting SPON1.

Mitochondrial OGG1 protects against PM2.5-induced oxidative DNA damage in BEAS-2B cells.

The enzyme 8-oxoguanine glycosylase 1 (OGG1) has been shown to be involved in the repair of oxidative DNA damage. However, the effect of OGG1 on oxidative DNA damage caused by particulate matter 2.5 (PM2.5) is unknown. Herein, we demonstrated that OGG1 could inhibit the generation of ROS and alleviate mitochondrial dysfunction and increased the expression of IL-1ß caused by PM2.5. The dichlorodihydrofluorescein diacetate (DCFH-DA) staining and 5,5',6,6'-tetrachloro-1,1',3,3'-. tetraethylbenzi-midazolylcarbocyanine iodide (JC-1) staining using flow cytometry showed that PM2.5 induces the generation of ROS and leads to a reduction in mitochondrial membrane potential (MMP) in BEAS-2B cells. Overexpression of OGG1 inhibited the generation of ROS and the decline in MMP. Knockdown of OGG1 by RNA interference (RNAi) increased the generation of ROS and reduced the MMP. Real-time quantitative PCR (RT-qPCR) for the mitochondrial DNA copy number (mtDNAcn) and flow cytometry for apoptosis revealed that OGG1 inhibits the apoptosis and decreases mtDNAcn induced by PM2.5. Additionally, the results of the comet assay showed that OGG1 had a significant repair effect on DNA strand breaks caused by PM2.5. Overexpression of OGG1 also significantly suppressed the expression of IL-1ß caused by PM2.5. Together, these data suggest that PM2.5 leads to mitochondrial dysfunction and the up-regulation of IL-1ß could be reversed by overexpression of OGG1. The mitochondrial dysfunction caused by PM2.5 could be relieved by OGG1. Thus, the base excision repair enzyme OGG1 may alleviate mitochondrial dysfunction caused by PM2.5 involved in the expression of IL-1ß.

FBXO31 promotes cell proliferation, metastasis and invasion in lung cancer.

FBXO31 is a member of F-box family which is involved in diverse biological functions and development of disease. Recent reports in breast cancer, hepatocellular carcinoma and ovarian cancer demonstrated inhibitory effect of FBXO31 on proliferation and tumorigenesis. However, the function of FBXO31 is not analyzed in lung cancer so far. In this study, we reported that expression of FBXO31 was higher in lung cancer tissues compared with non-cancerous lung tissues, and that higher expression of FBXO31 was significantly associated with tumor size, tumor infiltration, clinical stages and lymph node metastasis. In addition, exogenous expression of FBXO31 promoted cell growth, metastasis and invasion in A549 cells. Conversely, silencing FBXO31 by specific siRNA caused inhibitory effect on cell growth, metastasis and invasion. Moreover, tumorigenicity assays in nude mice showed FBXO31 promoted tumor growth in vivo. In conclusion, our data suggest FBXO31 promotes cell proliferation, metastasis and invasion in lung cancer.

Particulate matter 2.5 induces autophagy via inhibition of the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin kinase signaling pathway in human bronchial epithelial cells.

Particulate matter 2.5 (PM2.5) is a significant risk factor for asthma. A recent study revealed that autophagy was associated with asthma pathogenesis. However, the specific mechanisms underlying PM2.5-induced autophagy in asthma have remained elusive. In the present study, PM2.5-induced autophagy was evaluated in Beas-2B human bronchial epithelial cells and the potential molecular mechanisms were investigated. Using electron microscopy, immunofluorescence staining and immunoblot studies, it was confirmed that PM2.5 induced autophagy in Beas-2B cells as a result of PM2.5-mediated inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway in Beas-2B cells. LY294002, a PI3K inhibitor, reduced the accumulation of microtubule-associated protein 1 light chain 3 II and attenuated the effect of PM2.5. Phosphorylated (p-)p38, p-extracellular signal-regulated kinase and p-c-Jun N-terminal kinase were dephosphorylated following exposure to PM2.5. The roles of p53, reactive oxygen species scavenger tetramethylthiourea and autophagy inhibitor 3-methyladenine in PM2.5-induced autophagy in Beas-2B cells were also investigated. The results suggested that the PI3K/Akt/mTOR signaling pathway may be a key contributor to PM2.5-induced autophagy in Beas-2B cells. The results of the present study therefore provided an a insight into potential future clinical applications targeting these signaling pathways, for the prevention and/or treatment of PM2.5-induced lung diseases.

miR-5100 promotes tumor growth in lung cancer by targeting Rab6.

Our previous study demonstrated that microRNA 5100 (miR-5100) is overexpressed in lung cancer tissues; however, the function of miR-5100 remained elusive. In this study, we demonstrate that miR-5100 is highly expressed in a wide variety of lung cancer tissues and lung cancer cell lines. Exogenous expression of miR-5100 in A549 and H1299 lung cancer cells enhanced proliferation and colony formation, and conversely, suppression of miR-5100 exhibited inhibitory effects. Furthermore, we demonstrate that miR-5100 promotes tumor growth in nude mice. These effects may result from the ability of miR-5100 to promote G1/S transition and downregulate cyclin D1 and cyclin-dependent kinases 2 (CDK2) expressions in lung cancer stable cells. Using a bioinformatics target prediction tool, we identified Rab6 as a potential target of miR-5100. Consistently, overexpression of miR-5100 specifically reduced the expression of a luciferase reporter containing the predicted binding site from the 3'untranslated region (3'UTR) of Rab6 and decreased the accumulation of endogenous Rab6 in A549 and H1299 cells. Moreover, exogenous expression of Rab6 compromised the effects of miR-5100 on cell proliferation and colony formation. Our data suggest that miR-5100 promotes tumor growth by facilitating the G1/S transition and targeting Rab6.

AMPK is required for PM2.5-induced autophagy in human lung epithelial A549 cells.

The aim is to investigate the molecular mechanisms underlying the PM2.5-induced autophagy in human lung cancer epithelial cells (A549). The effects of the PM2.5 on morphological and biochemical markers of autophagy in A549 were analyzed by electron microscopy, GFP-LC3 puncta was observed by confocal fluorescence microscope. The effects of phosphorylation of AMPK, mTOR, AKT, ERK, JNK, and p53 on LC3II in A549 were observed following PM2.5 exposure; the role of autophagy in PM2.5-induced apoptosis was examined using 3-methyladenine and rapamycin. PM2.5 induced morphological and biochemical markers of autophagy in A549. Phosphorylation of AMPK and dephosphorylation of mTOR were observed following PM2.5 treatment, and AMPK inhibitor blocked LC3B-II expression. In addition, we demonstrated that PM2.5-induced autophagy confers a pro-survival role in host defense.

Mir-152 inhibits cell proliferation and colony formation of CD133(+) liver cancer stem cells by targeting KIT.

miR152 is involved in diverse biological functions and development of disease. This study investigates the role of mir-152 in cell proliferation and colony formation of liver cancer stem cells. We show that exogenous overexpression of mir-152 suppresses cell proliferation and colony formation in CD133(+) hep3B cells. We also show that KIT is a direct target of miR-152 and miR-152 downregulates protein expression of KIT by directly binding to 3' untranslated region of KIT. Downregulation of KIT by specific siRNAs inhibits proliferation and colony formation of CD133(+) hep3B cells, which is similar to inhibitory effects of miR-152. Moreover, exogenous expression of KIT compromises inhibitory effects of miR-152 on cell proliferation and colony formation. Our findings suggest that mir-152 inhibits cell proliferation and colony formation of CD133(+) hep3B cells by targeting KIT.

Five miRNAs as novel diagnostic biomarker candidates for primary nasopharyngeal carcinoma.

MicroRNAs (miRNAs) play an essential role in the development and progression of nasopharyngeal carcinomas (NPC). Despite advances in the field of cancer molecular biology and biomarker discovery, the development of clinically validated biomarkers for primary NPC has remained elusive. In this study, we investigated the expression and clinical significance of miRNAs as novel primary NPC diagnostic biomarkers. We used an array containing 2, 500 miRNAs to identify 22 significant miRNAs, and these candidate miRNAs were validated using 67 fresh NPC and 25 normal control tissues via quantitative real-time PCR (qRT-PCR). Expression and correlation analyses were performed with various statistical approaches, in addition to logistic regression and receiver operating characteristic curve analyses to evaluate diagnostic efficacy. qRT-PCR revealed five differentially expressed miRNAs (miR-93-5p, miR-135b-5p, miR-205-5p and miR-183-5p) in NPC tissue samples relative to control samples (p<0.05), with miR-135b-5p and miR-205-5p being of significant diagnostic value (p<0.01). Moreover, comparison of NPC patient clinicopathologic data revealed a negative correlation between miR-93-5p and miR- 183-5p expression levels and lymph node status (p<0.05). These findings display an altered expression of many miRNAs in NPC tissues, thus providing information pertinent to pathophysiological and diagnostic research. Ultimately, miR-135b-5p and miR-205-5p may be implicated as novel NPC candidate biomarkers, while miR- 93-5p, miR-650 and miR-183-5p may find application as relevant clinical pathology and diagnostic candidate biomarkers.