Planktonic microbial community and biological metabolism in a subtropical drinking water river-reservoir system.

To understand the dynamics of planktonic microbial community and its metabolism processes in subtropical drinking water river-reservoir system with lower man-made pollution loading, this study selected Dongzhen river-reservoir system in Mulan Creek as object to investigate spatial-temporal characteristics of community profile and functional genes involved in biological metabolism, and to analyze the influence of environmental factors. The results indicated that Proteobacteria and Actinobacteria were the most diverse phyla with proportion ranges of 9%-80% in target system, and carbohydrate metabolism (5.76-7.12 × 10-2), amino acid metabolism (5.78-7.21 × 10-2) and energy metabolism (4.07-5.17 × 10-2) were found to be the dominant pathways of biological metabolism. Although there were variations in biological properties both spatially and temporally, seasonal variation had a greater influence on microbial community and biological metabolism, than locational differences. Regarding the role of environmental factors, this study revealed that microbial diversity could be affected by multiple abiotic factors, with total organic carbon, total phosphorus and temperature being more influential (absolute value of standardized regression weights >2.13). Stochastic processes dominated the microbial community assembly (R2 of neutral community model = 0.645), while niche-based processes differences represented by nutrients, temperature and pH level played secondary roles (R > 0.388, P < 0.01). Notably, the synergistic influences among the environmental factors accounted for the higher percentages of community variation (maximum proportion up to 17.6%). Additionally, pH level, temperature, and concentrations of dissolved oxygen, carbon and nitrogen were found to be the significant factors affecting carbon metabolism pathways (P < 0.05), yet only total organic carbon significantly affected on nitrogen transformation (P < 0.05). In summary, the microbial profile in reservoir is not completely dominated by that in feeding river, and planktonic microbial community and its metabolism in subtropical drinking water river-reservoir system are shaped by multiple abiotic and biotic factors with underlying interactions.

LncRNA XR_595552 inhibition alleviates intermittent hypoxia-induced cardiomyocyte damage via activating the PI3K/AKT pathway.

BACKGROUND: Although the long noncoding RNAs (lncRNAs) expression profiles have been observed in previous study, the biological functions and underlying mechanisms of lncRNAs in OSA-related cardiac injury have not been elucidated. In the present study, we investigated a novel lncRNA, lncRNA XR_595552, and evaluated its role in intermittent hypoxia (IH)-induced damage in H9c2 cardiomyocytes. METHODS: H9c2 cells were exposed to IH condition. Real-time quantitative polymerase chain reaction (RT-qPCR) was conducted to measure the expression changes of lncRNA XR_595552 in H9c2 cells stimulated by IH. H9c2 cells were subjected to IH after transfection. CCK-8 was used to evaluate cell viability, and apoptosis was analyzed by Western blotting. Additionally, the regulatory relationship between lncRNA XR_595552 and PI3K/AKT was tested by RT-qPCR and Western blot. RESULTS: IH significantly induced injury in H9c2 cells (inhibited cell viability and promoted cell apoptosis). lncRNA XR_595552 was upregulated in a cell model of IH. Inhibition of lncRNA XR_595552 protected H9c2 cells against IH-induced damage, as the viability was increased, Bax, Caspase-9, and Caspase-3 were downregulated, and Bcl-2 was upregulated. More interestingly, lncRNA XR_595552 downregulation activated the PI3K/AKT pathway. Blocking the PI3K/AKT signal pathway by the use of LY294002 eliminated the myocardioprotective effects of lncRNA XR_595552 in H9c2 cells under IH condition. CONCLUSIONS: The results show that lncRNA XR_595552, a novel lncRNA, may play a protective role in attenuating IH-induced injury in cardiomyocytes via a regulating PI3K/AKT pathway. The findings suggest that this lncRNA could serve as a therapeutic target to treat OSA-related cardiovascular disorders.

FUT3 facilitates glucose metabolism of lung adenocarcinoma via activation of NF-κB pathway.

OBJECTIVE: Fucosyltransferases (FUTs) molecules have been identified to be involved in carcinogenesis of malignant tumors. Nevertheless, the biological function of fucosyltransferases-3 (FUT3) in lung adenocarcinoma (LUAD) malignant phenotype remains unclear. Herein, we investigated the association between FUT3 and LUAD pathological process. METHODS: Immunochemistry, RT-qPCR and western blot assays were conducted to evaluate the expression of FUT3 in LUAD and corresponding adjacent tissues. The prognostic value of FUT3 was assessed via Kaplan­Meier plotter database. The biological process and potential mechanism of FUT3 in LUAD were conducted via GSEA. Additionally, immunofluorescence and metabolite activity detection were performed to determine the potential role of FUT3 in LUAD glucose metabolism. The active biomarkers associated with NF-κB signaling pathway were detected via western blot. Subcutaneous tumor model was conducted to analyze the effect of FUT3 on tumorigenesis of LUAD. RESULTS: FUT3 was remarkably upregulated in LUAD tissues compared with adjacent tissues from individuals. FUT3 overexpression may predict poor prognosis of LUAD patients. Knockdown of FUT3 significantly inhibited tumor proliferation, migration and glucometabolic alteration in LUAD cells. Moreover, GSEA demonstrated that elevated FUT3 was positively related to NF-κB signaling pathway. Additionally, in vitro and in vivo assays also indicated that downregulation of FUT3 resulted in the suppression of oncogenesis and glucose metabolism via inactivation of NF-κB pathway. CONCLUSION: Our findings demonstrated that FUT3 was involved in glucometabolic process and tumorigenesis of LUAD via NF-κB signaling pathway. FUT3 may be an optimal target for diagnosis and treatment of LUAD patients.

Identification of a ZC3H12D-regulated competing endogenous RNA network for prognosis of lung adenocarcinoma at single-cell level.

BACKGROUND: To identify hub genes from the competing endogenous RNA (ceRNA) network of lung adenocarcinoma (LUAD) and to explore their potential functions on prognosis of patients from a single-cell perspective. METHODS: We performed RNA-sequencing of LUAD to construct ceRNA regulatory network, integrating with public databases to identify the vital pathways related to patients' prognosis and to reveal the expression level of hub genes under different conditions, the functional enrichment of co-expressed genes and their potential immune-related mechanisms. RESULTS: ZC3H12D-hsa-miR-4443-ENST00000630242 axis was found to be related with LUAD. Lower ZC3H12D expression was significantly associated with shorter overall survival (OS) of patients (HR = 2.007, P < 0.05), and its expression was higher in early-stage patients, including T1 (P < 0.05) and N0 (P < 0.05). Additionally, ZC3H12D expression was higher in immune cells displayed by single-cell RNA-sequencing data, especially in Treg cells of lung cancer and CD8 T cells, B cells and CD4 T cells of LUAD. The functional enrichment analysis showed that the co-expressed genes mainly played a role in lymphocyte activation and cytokine-cytokine receptor interaction. In addition, ZC3H12D was associated with multiple immune cells and immune molecules, including immune checkpoints CTLA4, CD96 and TIGIT. CONCLUSION: ZC3H12D-hsa-miR-4443-ENST00000630242 ceRNA network was identified in LUAD. ZC3H12D could affect prognosis of patients by regulating mRNA, miRNA, lncRNA, immune cells and immune molecules. Therefore, it may serve as a vital predictive marker and could be regarded as a potential therapeutic target for LUAD in the future.

An integrated analysis of the competing endogenous RNA network associated of prognosis of stage I lung adenocarcinoma.

BACKGROUND: Accumulating evidence indicates that long non-coding RNAs (lncRNAs) are involving in the tumorigenesis and metastasis of lung cancer. The aim of the study is to systematically characterize the lncRNA-associated competing endogenous RNA (ceRNA) network and identify key lncRNAs in the development of stage I lung adenocarcinoma (LUAD). METHODS: Totally, 1,955 DEmRNAs, 165 DEmiRNAs and 1,107 DElncRNAs were obtained in 10 paired normal and LUAD tissues. And a total of 8,912 paired lncRNA-miRNA-mRNA network was constructed. Using the Cancer Genome Atlas (TCGA) dataset, the module of ME turquoise was revealed to be most relevant to the progression of LUAD though Weighted Gene Co-expression Network Analysis (WGCNA). RESULTS: Of the lncRNAs identified, LINC00639, RP4-676L2.1 and FENDRR were in ceRNA network established by our RNA-sequencing dataset. Using univariate Cox regression analysis, FENDRR was a risk factor of progression free survival (PFS) of stage I LUAD patients (HRs = 1.69, 95%CI 1.07-2.68, P < .050). Subsequently, diffe rential expression of FENDRR in paired normal and LUAD tissues was detected significant by real-time quantitative (qRT-PCR) (P < 0.001). CONCLUSIONS: This study, for the first time, deciphered the regulatory role of FENDRR/miR-6815-5p axis in the progression of early-stage LUAD, which is needed to be established in vitro and in vivo.

C1QTNF6 regulated by miR-29a-3p promotes proliferation and migration in stage I lung adenocarcinoma.

OBJECTIVE: C1QTNF6 has been implicated as an essential component in multiple cellular and molecular preliminary event, including inflammation, glucose metabolism, endothelial cell modulation and carcinogenesis. However, the biological process and potential mechanism of C1QTNF6 in lung adenocarcinoma (LUAD) are indefinite and remain to be elucidated. Therefore, we investigated the interaction among the traits of C1QTNF6 and LUAD pathologic process. METHODS: RT-qPCR and western blot were conducted to determine the expression levels of C1QTNF6. RNA interference and overexpression of C1QTNF6 were constructed to identify the biological function of C1QTNF6 in cellular proliferative, migratory and invasive potentials in vitro. Dual-luciferase reporter assay was applied to identify the possible interaction between C1QTNF6 and miR-29a-3p. Moreover, RNA sequencing analysis of C1QTNF6 knockdown was performed to identify the potential regulatory pathways. RESULTS: C1QTNF6 was upregulated in stage I LUAD tissues compared with adjacent non-cancerous tissues. Concurrently, C1QTNF6 knockdown could remarkably inhibit cell proliferation, migratory and invasive abilities, while overexpression of C1QTNF6 presented opposite results. Additionally, miR-29a-3p may serve as an upstream regulator of C1QTNF6 and reduce the expression of C1QTNF6. Subsequent experiments showed that miR-29a-3p could decrease the cell mobility and proliferation positive cell rates, as well as reduce the migratory and invasive possibilities in LUAD cells via downregulating C1QTNF6. Moreover, RNA sequencing analysis demonstrated that the cytokine-cytokine receptor interaction pathway may participate in the process of C1QTNF6 regulating tumor progression. CONCLUSION: Our study first demonstrated that downregulation of C1QTNF6 could inhibit tumorigenesis and progression in LUAD cells negatively regulated by miR-29a-3p. These consequences could reinforce our awareness and understanding of the underlying mechanism and provide a promising therapeutic target for LUAD.

Impact of CPAP treatment for obstructive sleep apnea on visceral adipose tissue: a meta-analysis of randomized controlled trials.

BACKGROUND: It is still controversial if the continuous positive airway pressure (CPAP) treatment for patients with obstructive sleep apnea (OSA) can markedly influence an effect on visceral adipose tissue (VAT). The current study aimed to assess the efficacy of CPAP interventions in reducing VAT in OSA patients. METHODS: The Web of Science, PubMed, Embase, and Cochrane Library (up to December, 2019) were searched for randomized trials that assessed the effect of CPAP therapy in decreasing VAT in OSA patients. Information on the study, pre- and post-CPAP treatment of VAT, and patient characteristics were extracted for analysis. The standardized mean difference (SMD) was applied to measure the summary estimates. The analysis was conducted with STATA 13.0 and RevMan v.5.3. RESULTS: Five studies (6 cohorts) that involved 169 patients were enrolled in the meta-analysis. There was no significant change of VAT in patients with OSA before and after CPAP treatment (SMD = - 0.00, 95% CI = - 0.21 to 0.21, z = 0.01, p = 0.99). Subgroup analyses further demonstrated that the results were not influenced by CPAP therapy duration, patient age, sample size, or baseline body mass index. CONCLUSIONS: Among the patients with OSA, our meta-analysis revealed that treatment with CPAP does not significantly lead to a reduction of VAT. High-quality randomized controlled trials may provide further clarifying information.

Effects of CPAP therapy on subcutaneous adipose tissue in patients with obstructive sleep apnea: a meta-analysis.

PURPOSE: Continuous positive airway pressure (CPAP) is an effective treatment for obstructive sleep apnea (OSA). However, studies provide conflicting results on the effects of CPAP on subcutaneous adipose tissue (SAT) in patients with OSA. We therefore performed a meta-analysis to evaluate whether or not CPAP has an effect on SAT in patients with OSA. METHODS: Studies were retrieved by searching the Cochrane Library, Web of Science, Embase, and Pubmed. Information on study and patient characteristics, study design, and SAT pre- and post-CPAP treatment was extracted for analysis. Different methods for measurement of SAT were also notated. Standardized mean difference (SMD) and 95% confidence interval (CI) were measured to estimate the change in SAT before and after CPAP treatment. Meta-analysis was performed using the RevMan v.5.3 and Stata 14.0. RESULTS: A total of 10 studies met inclusion criteria encompassing 309 patients in the final analysis. The pooled estimate showed that CPAP treatment resulted in no significant change in SAT (SMD = - 0.014, 95% CI = - 0.161 to 0.133, p = 0.896). Meta-regression analyses revealed no predictor, including methods of measuring SAT, that influenced the CPAP effect on SAT. CONCLUSION: Our meta-analysis demonstrated that after CPAP therapy, there was no significant change in SAT in patients with OSA.

Effects of CPAP on visceral adipose tissue in patients with obstructive sleep apnea: a meta-analysis.

PURPOSE: The efficacy of obstructive sleep apnea (OSA) treatment with continuous positive airway pressure (CPAP) on visceral adipose tissue (VAT) yielded conflicting results. This meta-analysis was performed to assess whether OSA treatment with CPAP could reduce VAT. METHODS: The PubMed, Cochrane Library, Embase, and Web of Science were searched before April 2019. Information on characteristics of study participants, pre- and post-CPAP treatment of VAT, and study design was utilized for analysis. Standardized mean difference (SMD) and 95% confidence interval (CI) were used to fully analyze the overall effects. Eleven studies were obtained and the meta-analysis was performed using RevMan v.5.2 and STATA 12.0. RESULTS: A total of 11 studies (16 cohorts) were pooled into meta-analysis, which included 398 patients. The value of VAT before and after CPAP treatment showed no change in OSA patients (SMD = - 0.02, 95% CI - 0.16 to 0.12, z = 0.24, p = 0.81). Subgroup analyses were further conducted, which revealed that age, gender distribution, baseline body mass index, daily duration, CPAP therapy duration, measure, sample size, and study design did not affect the results. CONCLUSIONS: This meta-analysis revealed that CPAP therapy has no effect on VAT in OSA patients. Further large-scale, well-designed randomized controlled trials are required to address this issue.

Effect of chronic intermittent hypoxia on gene expression profiles of rat liver: a better understanding of OSA-related liver disease.

PURPOSE: Obstructive sleep apnea (OSA) and OSA-associated chronic intermittent hypoxia (CIH) have been suggested to be associated with increased risk of liver disease. Little is known about the biological pathophysiology and underlying molecular mechanisms. Here we use whole-genome expression profiling to explore the transcriptomic changes induced by CIH in rat liver. METHODS: Rats (n = 3) were exposed to CIH for 8 weeks and were compared with rats exposed to normoxia (n = 3). Illumina HiSeq 4000 platform was used to examine differentially expressed genes (DEGs) in the liver between control group and CIH rat model. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate DEGs. Biological functions of DEGs were determined by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. RESULTS: Compared with control group, 318 genes were identified to be dysregulated in the liver of CIH rat model, with 211genes upregulated and 107 genes downregulated. Bioinformatics analysis showed that these genes were extensively related to various physiologic processes such as hepatic metabolism, apoptotic process, and oxidative stress. 10 genes with 5 upregulated and 5 downregulated were selected and further verified by qRT-PCR. CONCLUSIONS: CIH resulted in altered gene expression patterns in the liver of rat. The DEGs were related to various physiological and pathological processes in CIH rat liver. These data provide a better understanding of the mechanisms and underlying molecular changes of OSA-related liver disease.

Expression profile of long non-coding RNAs in rat models of OSA-induced cardiovascular disease: new insight into pathogenesis.

PURPOSE: Long non-coding RNAs (lncRNAs) are a recently identified class of regulatory molecules involved in the regulation of numerous biological processes, but their functions in a rat model of chronic intermittent hypoxia (CIH) remain largely unknown. Therefore, for further investigation, we aimed to explore lncRNA expression profiles and reveal their potential functional roles in rat models of CIH. METHODS: We used a well-established CIH rat model and conducted lncRNA microarray experiments on the heart samples of rats with CIH and under normoxia control. Differentially expressed lncRNAs and mRNAs were identified via fold-change filtering and verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Bioinformatics analyses were applied to reveal the potential roles of key lncRNAs. Co-expression analysis was conducted to determine the transcriptional regulatory relationship of lncRNAs and mRNAs between the two groups. RESULTS: Our data indicated that 157 lncRNAs and 319 mRNAs were upregulated, while 132 lncRNAs and 428 mRNAs were downregulated in the rat model of CIH compared with sham control. Pathway analyses showed that 31 pathways involved in upregulated transcripts and 28 pathways involved in downregulated transcripts. Co-expression networks were also constructed to explore the potential roles of differentially expressed lncRNAs on mRNAs. LncRNAs, namely, XR_596701, XR_344474, XR_600374, ENSRNOT00000065561, XR_590196, and XR_597099, were validated by the use of qRT-PCR. CONCLUSIONS: The present study first revealed lncRNAs expression profiles in a rat model of CIH, providing new insight into the pathogenesis of obstructive sleep apnea-induced cardiovascular disease.

Effect of continuous positive airway pressure on endothelin-1 in patients with obstructive sleep apnea: a meta-analysis.

PURPOSE: Obstructive sleep apnea (OSA) is related to endothelin-1 (ET-1). Continuous positive airway pressure (CPAP) is an effective therapy for OSA. However, the effectiveness of CPAP on ET-1 levels in patients with OSA yielded contradictory results. We conducted a meta-analysis to assess the effect of CPAP on ET-1 levels in OSA. METHODS: The Embase, and Cochrane Library and PubMed were searched before March, 2018. The overall effects were measured by the standardized mean difference (SMD) with a 95% confidence interval (CI). Ten studies were included and the meta-analysis was conducted using Stata 14.0. RESULTS: 10 studies involving 375 patients were included in the meta-analysis. The result showed that there was a significant reduction in ET-1 levels in OSA patients before and after CPAP therapy (SMD = - 0.74, 95% CI = - 1.30 to - 0.17, z = 2.56, p = 0.01). Further, subgroup analysis demonstrated that Apnea-Hypopnea Index (AHI), CPAP therapy duration, and sample size also affected CPAP therapy. CONCLUSIONS: Our meta-analysis indicated that CPAP treatment among OSA patients was significantly was related to a decrease in ET-1 levels. Further prospective long-term studies with a larger number of patients are needed to evaluate and clarify this issue.

DAX-1 inhibits hepatocellular carcinoma proliferation by inhibiting ß-catenin transcriptional activity.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) represents the most common type of liver cancer. DAX1 (dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on X chromosome, gene 1), an atypical member of the nuclear receptor family due to lack of classical DNA-binding domains, has been known for its fundamental roles in the development, especially in the sex determination and steroidogenesis. Previous studies also showed that DAX-1 played a critical role in endocrine and sex steroid-dependent neoplasms such as adrenocortical, pituitary, endometrial, and ovarian tumors. However, its biological roles in the development of HCC remain largely unexplored. METHODS: Real-time PCR and Western blot were used to detect the expression of DAX-1 in HCC tissues and cell lines. Immunoprecipitation (IP) assay was used to show the interaction between DAX-1 and ß-Catenin. Small interfering RNA (siRNA) was used to silence the expression of DAX-1. BrdU incorporation and Cell-cycle assays were used to detect the role of DAX-1 in HCC cells proliferation. Migration and invasion assays were carried out to test the metastasis ability of DAX-1 in HCC cells. RESULTS: In the present study, we found that mRNA and protein levels of DAX-1 were down-regulated in HCC tissues and cell lines. Furthermore, overexpression of DAX-1 could inhibit while its knockdown using small interfering RNA promoted cell proliferation in several HCC cell lines. At the molecular level, we demonstrated that DAX-1 could interact with ß-Catenin and attenuate its transcriptional activity. CONCLUSION: Therefore, our results suggest a previously unknown DAX-1/ß-Catenin molecular network controlling HCC development.

MicroRNA-195 regulates steroid receptor coactivator-3 protein expression in hepatocellular carcinoma cells.

Multiple studies have shown that steroid receptor coactivator-3 (SRC-3) is upregulated and promotes cell proliferation in several human cancers, including breast, lung, and prostate carcinoma. However, its molecular determinants remain largely unexplored. In the current study, by way of informatics software, we found that MicroRNA-195 (miR-195) could negatively regulate protein levels of SRC-3 through targeting its 3'-untranslated region (3'-UTR) in hepatocellular carcinoma (HCC) cells. As a result, miR-195 mimics inhibited while its antisense enhanced SRC-3 protein levels. Furthermore, miR-195 could modulate cell proliferation and tumor growth in vivo and in vitro. Therefore, our results demonstrate a novel molecular mechanism for the dysregulated expression of SRC-3 in hepatocellular carcinoma.

Comprehensive analysis of prognostic value and immune infiltration of Regulator of Chromosome Condensation 2 in lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) incidence and mortality take the leading place of most malignancies. Previous studies have revealed the regulator of chromosome condensation 1 (RCC1) family members played an essential role during tumorigenesis. However, its biological functions in LUAD still need further investigation. Methods: Several databases were applied to explore potential effects of RCC1 family members on LUAD, such as Oncomine, GEPIA, and cBioPortal. Real-time PCR and immunohistochemistry were used to verify the expression of RCC2 in stage I LUAD. H1975 and A549 were selected to explore the biological function of RCC2 in cellular malignant phenotype. Results: The expressions of RCC1 and RCC2 showed marked differences in malignant tissue compared to lung tissue. The higher the expression levels of RCC1 or RCC2 in LUAD patients, the shorter their overall survival (OS). In normal lung tissues, RCC1 expression was highly enriched in alveolar cells and endothelial cells. Compare with RCC1, RCC2 expression in normal lung tissue was significantly enriched in macrophages, B cells and granulocytes. Additionally, RCC2 expression level was correlated with multiple immune cell infiltration in LUAD. Moreover, the mutation or different sCNA status of RCC2 exerted influence on multiple immune cell infiltration distribution. We found that the upregulation of RCC1 and RCC2 were obviously related to TP53 mutation. GSEA analysis revealed that RCC2 was involved in the process of DNA replication, nucleotide excision repair and cell cycle, which might affect tumor progression through P53 signaling pathway. We further elucidated that downregulation of RCC2 could dramatically repress the migration and invasion of LUAD cells. Conclusions: The study demonstrated that RCC1 and RCC2 expression were markedly increased in early-stage of LUAD. Patients with high expression of RCC1 or RCC2 had a worse prognosis. Based on our analysis, RCC1 and RCC2 might exert influence on LUAD process through DNA replication, nucleotide excision repair and cell cycle, as well as cells migration and invasion. Different from RCC1, RCC2 also involved in immune infiltration. These analyses provided a novel insight into the identification of diagnostic biomarker.

PPAR-γ/NF-kB/AQP3 axis in M2 macrophage orchestrates lung adenocarcinoma progression by upregulating IL-6.

Aquaporin 3 (AQP3), which is mostly expressed in pulmonary epithelial cells, was linked to lung adenocarcinoma (LUAD). However, the underlying functions and mechanisms of AQP3 in the tumor microenvironment (TME) of LUAD have not been elucidated. Single-cell RNA sequencing (scRNA-seq) was used to study the composition, lineage, and functional states of TME-infiltrating immune cells and discover AQP3-expressing subpopulations in five LUAD patients. Then the identifications of its function on TME were examined in vitro and in vivo. AQP3 was associated with TNM stages and lymph node metastasis of LUAD patients. We classified inter- and intra-tumor diversity of LUAD into twelve subpopulations using scRNA-seq analyses. The analysis showed AQP3 was mainly enriched in subpopulations of M2 macrophages. Importantly, mechanistic investigations indicated that AQP3 promoted M2 macrophage polarization by the PPAR-γ/NF-κB axis, which affected tumor growth and migration via modulating IL-6 production. Mixed subcutaneous transplanted tumor mice and Aqp3 knockout mice models were further utilized, and revealed that AQP3 played a critical role in mediating M2 macrophage polarization, modulating glucose metabolism in tumors, and regulating both upstream and downstream pathways. Overall, our study demonstrated that AQP3 could regulate the proliferation, migration, and glycometabolism of tumor cells by modulating M2 macrophages polarization through the PPAR-γ/NF-κB axis and IL-6/IL-6R signaling pathway, providing new insight into the early detection and potential therapeutic target of LUAD.

Association between X-ray repair cross-complementation group 1 rs25487 polymorphism and pancreatic cancer risk.

Previous published studies suggested that genetic polymorphisms in DNA repair genes could modify the DNA repair capacity and could be associated with pancreatic cancer risk. However, previous studies on the association between X-ray repair cross-complementation group 1 (XRCC1) rs25487 (Arg399Gln) polymorphism and pancreatic cancer risk reported inconsistent results. To obtain a more precise estimation of the association between XRCC1 rs25487 polymorphism and pancreatic cancer risk, we performed a meta-analysis of previous published studies by calculating the pooled odds ratio (OR) with a 95% confidence interval (95% CI). Eight individual studies with 5,542 subjects from six publications were finally included into this meta-analysis. The meta-analysis of total eight studies showed that there was no association between XRCC1 rs25487 polymorphism and pancreatic cancer risk in total population under all four genetic models (Gln versus Arg: OR = 1.10, 95% CI 0.95-1.28, P = 0.199; GlnGln versus ArgArg: OR = 1.15, 95% CI 0.93-1.41, P = 0.191; GlnGln/ArgGln versus ArgArg: OR = 1.10, 95% CI 0.97-1.25, P = 0.127; GlnGln versus ArgArg/ArgGln: OR = 1.12, 95% CI 0.92-1.36, P = 0.253). Subgroup analysis showed that there was no association between XRCC1 rs25487 polymorphism and pancreatic cancer risk in Caucasians, but XRCC1 rs25487 polymorphism was associated with pancreatic cancer risk in Asians (GlnGln/ArgGln versus ArgArg: OR = 1.24, 95% CI 1.01-1.53, P = 0.040). Therefore, the meta-analysis suggests that XRCC1 rs25487 polymorphism is associated with pancreatic cancer risk in Asians. Further studies with more participants are needed to provide a more precise estimation on the association above.

Celastrol exerts synergistic effects with PHA-665752 and inhibits tumor growth of c-Met-deficient hepatocellular carcinoma in vivo.

PHA665752 (PHA), a selective small molecule c-Met Inhibitor, potently inhibited HGF-stimulated and constitutive c-Met phosphorylation, as well as HGF and c-Met-driven phenotypes of a variety of tumor cells including hepatocellular carcinoma cells. However, these effects were impaired in c-Met-deficient cancer cells. In the present study, we investigated the potential anti-human c-Met-deficient hepatocellular carcinoma effects of Celastrol, a novel triterpene, and its combination with PHA. Human hepatocellular carcinoma cells BEL-7402 (c-Met-positive) and Huh7 (c-Met-deficient) were treated with different dose of PHA with or without equal dose of Celastrol, and cell growth, cell cycle and apoptosis were evaluated, respectively, by MTT assay, flow cytometry and Caspase3/7 activity. Nude mice bearing Huh7 xenografts were used to assess the in vivo anti-tumor activity. Our results showed that Celastrol at high concentration (>1.0 µM) induced G2/M arrest and apoptosis with the activation of Caspase3/7 in Huh7 cells whereas at low concentration (<1.0 µM) had no obvious effects. Low concentration Celastrol presented significant combined effects with PHA on Huh7 cells and Huh7 xenografts in terms of growth inhibition, migration inhibition and apoptosis induction. These results suggest that Celastrol and its combination with PHA present the therapeutic potential on c-Met-deficient hepatocellular carcinoma, and deserve further preclinical and clinical studies.

Thyroid Dysfunction in Non-Small Cell Lung Cancer With Immune Checkpoint Inhibitors: A Meta-Analysis.

Immune checkpoint inhibitors (ICIs) have been established as the cornerstone for advanced non-small cell lung cancer, while thyroid adverse events (AEs) associated with ICIs have not been systematically documented. Therefore, we performed a meta-analysis to evaluate the effect of ICI applications on the thyroid of patients with non-small cell lung cancer. We performed a systematic search of PubMed, the Cochrane Library, Web of Science, and Embase for eligible randomized controlled trials up to December 2021. Clinical trials reporting thyroid AEs including hypothyroidism, hyperthyroidism, and thyroiditis were enrolled. The I2  statistic was also calculated to quantify the heterogeneity. Data were evaluated as risk ratio (RR) and corresponding 95%CIs. A total of 10 randomized clinical trials involving 6154 patients were included in this meta-analysis. ICI application was found to have a statistically significant higher risk of all grade hypothyroidism (RR, 7.03; P < 0.0001), hyperthyroidism (RR, 4.88; P < 0.0001), and thyroiditis (RR, 6.58; P = 0.0014) compared with the chemotherapy group. Moreover, we demonstrated that second-line therapy significantly increased the risk of all-grade hypothyroidism (RR, 7.03 [95%CI, 4.69-10.55]) and hyperthyroidism (RR, 4.88 [95%CI, 3.11-7.65]). Our meta-analysis manifested that regimens with ICIs may significantly increase all grades of hypothyroidism, hyperthyroidism, and thyroiditis. ICIs may induce the occurrence and exacerbation of endocrine AEs compared with chemotherapy.

Expression alteration of serum exosomal circular RNAs in obstructive sleep apnea patients with acute myocardial infarction.

PURPOSE: Circular RNAs (circRNAs) are recently identified as a class of non-coding RNAs that participate in the incidence of acute myocardial infarction (AMI). However, circRNAs expression pattern in obstructive sleep apnea (OSA) with AMI remains unknown. The aim was to investigate circRNAs expression alteration in serum exosomes derived from OSA patients with AMI. METHODS: The serum exosomal circRNAs profile of three healthy subjects, three OSA without AMI and three OSA with AMI were analyzed using high-throughput sequencing. Bioinformatic analyses were carried out to assess potential core circRNAs and functional analyses were conducted to study biological functions. RESULTS: Compared to healthy subjects, there were 5225 upregulated and 5798 downregulated circRNAs in exosomes from OSA with AMI patients. And our study also identified 5210 upregulated and 5813 downregulated circRNAs in OSA with AMI patients compared to OSA without AMI. The differential expression of 2 circRNAs (hsa_circRNA_101147, hsa_circRNA_101561) between healthy subjects and OSA without AMI, and 4 circRNAs (hsa_circRNA_101328, hsa_circRNA_104172, hsa_circRNA_104640, hsa_circRNA_104642) between healthy subjects and OSA with AMI were confirmed by qRT-PCR. In addition, we demonstrated that miR-29a-3p targeted hsa_circRNA_104642 directly. CONCLUSIONS: This study demonstrated that there were a number of dysregulated circRNAs in exosomes from OSA with AMI patients, which might be effectively served as a promising diagnostic biomarker and therapeutic targets.