Association between dietary vitamin C intake/blood level and risk of digestive system cancer: a systematic review and meta-analysis of prospective studies.

Experimental studies have shown that vitamin C has anti-cancer effects, but previous meta-analyses have indicated that the role of vitamin C in digestive system cancers (DSCs) is controversial. In this study, a systematic review and meta-analysis of the relationship between dietary intake/plasma concentration of vitamin C and the risk of DSC was conducted, evaluating 32 prospective studies with 1 664 498 participants. Dose-response and subgroup analyses were also performed. Systematic literature searches were performed in PubMed, EMBASE and Web of Science databases until 9th September 2023. Vitamin C intake significantly reduced DSCs risk (RR = 0.88, 95% confidence interval (CI) 0.83 to 0.93). The subgroup analyses showed the risks of oral, pharyngeal, and esophageal (OPE) cancers (0.81, 0.72 to 0.93), gastric cancer (0.81, 0.68 to 0.95), and colorectal cancer (0.89, 0.82 to 0.98) were negatively correlated with vitamin C intake, and the effect of vitamin C was different between colon cancer (0.87, 0.77 to 0.97) and rectal cancer (1.00, 0.84 to 1.19). However, plasma vitamin C concentration was only inversely associated with gastric cancer risk (0.74, 0.59 to 0.92). Dose-response analysis revealed that 250 and 65 mg day-1 vitamin C intakes had the strongest protective effect against OPE and gastric cancers respectively. These estimates suggest that vitamin C intake could significantly reduce gastrointestinal cancer incidence, including OPE, gastric, and colon cancers. Plasma vitamin C has a significant reduction effect on the incidence of gastric cancer only, but additional large-scale clinical studies are needed to determine its impact on the incidence of DSCs.

Evaluating the efficacy of GIPR agonists on non-alcoholic fatty liver disease: A Mediation Mendelian Randomization Study.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is becoming the most common chronic liver disease worldwide while still lacks drugs for treatment or prevention. We aimed to investigate the causal role of glucose-dependent insulinotropic polypeptide receptor agonists (GIPRAs) on NAFLD and identify the mediated risk factors by which GIPRAs exert their therapeutic effects. METHODS: Genetic proxies of GIPRAs were identified as cis-SNPs of GIPR associated with both the gene expression level and HbA1c and analyses including colocalization and linkage disequilibrium (LD) were performed for validation. We then performed two-sample two-step mendelian randomization to determine the causal effect of GIPRAs on NAFLD. RESULTS: The MR analysis suggested genetic proxies of GIPRAs were causally associated with reduced risk of NAFLD (Odds ratio (OR): 0.46, 95 % confidence interval (95 % CI): 0.24-0.88, P = 0.02) and T2DM (OR: 0.10, 95 % CI: 0.07-0.13, P < 0.01). In addition, Mediation analysis showed evidence of indirect effect of GIPRAs on NAFLD via TRIG (0.88, [0.85-0.92], P < 0.01) and HDL-C (0.85, [0.80-0.90], P < 0.01). CONCLUSIONS: Our study provided strong evidence to support the causal role of GIPRAs on reducing the risk of NAFLD probably through improving lipid metabolism, especially TG and HDL-C, providing guidance for future clinical trials.

Predictive value of the geriatric nutrition risk index for postoperative delirium in elderly patients undergoing cardiac surgery.

AIMS: The aims of the study were to determine the relationship between preoperative geriatric nutritional risk index (GNRI) and the occurrence of postoperative delirium (POD) in elderly patients after cardiac surgery and to evaluate the additive value of GNRI for predicting POD. METHODS: The data were extracted from the Multiparameter Intelligent Monitoring in Intensive Care (MIMIC-IV) database. Patients who underwent cardiac surgery and were aged 65 or older were included. The relationship between preoperative GNRI and POD was investigated using logistic regression. We determined the added predictive value of preoperative GNRI for POD by measuring the changes in the area under the receiver operating characteristic curve (AUC) and calculating the net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: A total of 4286 patients were included in the study, and 659 (16.1%) developed POD. Patients with POD had significantly lower GNRI scores than patients without POD (median 111.1 vs. 113.4, p < 0.001). Malnourished patients (GNRI ≤ 98) had a significantly higher risk of POD (odds ratio, 1.83, 90% CI, 1.42-2.34, p < 0.001) than those without malnutrition (GNRI > 98). This correlation remains after adjusting for confounding variables. The addition of GNRI to the multivariable models slightly but not significantly increases the AUCs (all p > 0.05). Incorporating GNRI increases NRIs in some models and IDIs in all models (all p < 0.05). CONCLUSIONS: Our results showed a negative association between preoperative GNRI and POD in elderly patients undergoing cardiac surgery. The addition of GNRI to POD prediction models may improve their predictive accuracy. However, these findings were based on a single-center cohort and will need to be validated in future studies involving multiple centers.

Influence of Primary Tumor Resection on Survival of Patients With Metastatic Siewert Type II Adenocarcinoma of the Esophagogastric Junction: A Population-Based, Propensity-Matched Analysis.

OBJECTIVE: It remains unclear whether primary tumor resection improves survival in patients with metastatic Siewert type II adenocarcinoma of the esophagogastric junction (AEG). Therefore, our study attempted to investigate the prognostic value of primary tumor resection on metastatic AEG. METHODS: In total, 4200 patients diagnosed with metastatic AEG were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015. Patients were categorized into two groups according to the performance of primary tumor resection. Pearson's chi-square test, Kaplan-Meier survival curve, and Cox regression analysis were conducted in this study. In addition, propensity-score matching was conducted to match 323 patients who received primary tumor resection and another 323 patients without. RESULTS: Multivariate Cox regression analysis demonstrated that primary tumor resection was a significant prognostic factor in patients with metastatic AEG before matching. Moreover, in the matched cohort, metastatic AEG patients receiving primary tumor resection had significantly longer overall survival (hazard ratio [HR]: .54, 95% confidence interval [CI]: .46-.64, P < .001) and cancer-specific survival (HR: .53, 95% CI: .45-.63, P < .001). Subgroup analysis similarly revealed that primary tumor resection was significantly associated with better survival in most subgroups. CONCLUSION: The present population-based study identified that primary tumor resection led to significantly superior survival in patients with metastatic AEG. These findings are likely to contribute to the development of individualized therapy in metastatic AEG.

Physicochemical properties of environmental media can affect the adsorption of arsenic (As) by microplastics.

Microplastics are emerging pollutants that can adsorb heavy metals and threaten human health through food chain. Recently, there has been increasing interest in understanding the adsorption behavior of heavy metals by microplastics in farmland soil. In particular, arsenic (As), as a carcinogen, has the potential to be adsorbed by soil microplastics. However, the mechanisms and controlling factors of As adsorption by microplastics in farmland soil under natural conditions are still unknown. Here, microplastics and As were respectively added to farmland soils with different physicochemical properties from twelve provinces of China for adsorption experiment. We performed surface analysis of microplastics, quantified As accumulation through quasi-first-order kinetic equation and developed regression models to screen the factors controlling As adsorption. The results showed that the adsorption of As by soil microplastics was a chemical process accompanied by the loss of electrons from oxygen-containing functional groups. Soil cation exchange capacity (CEC) was the main factor controlling the adsorption rate, while soil organic matter (SOM), total nitrogen (TN) and CEC mainly influenced the equilibrium adsorption capacity. This is the first report on microplastic-As adsorption in natural soil, which allows deeper insights into risk assessment, prediction and control of microplastic-As pollution in agricultural soil.

Colquhounia Root Tablet Promotes Autophagy and Inhibits Apoptosis in Diabetic Nephropathy by Suppressing CD36 Expression In Vivo and In Vitro.

Methods: Rat models of DN were established using streptozotocin (STZ). The primary metabolic parameters were assessed. The pathological changes of the rat kidney were investigated, and RNA sequencing was performed for each group. Renal tissue apoptosis was detected using the TUNEL assay. In rats and high glucose- (Hg-) induced HK-2 cells, RT-qPCR and western blot were used to analyze the expression of related genes and proteins. Hg medium was used to establish the diabetic kidney environment. The CCK-8 assay and flow cytometry were used to assess cell viability and apoptosis, respectively. Transmission electron microscopy was used to evaluate autophagy in vitro. Results: CRT treatment significantly reduced albuminuria and renal tissue damage in DN rats. Furthermore, CRT administration inhibited apoptosis and promoted autophagy in DN rat kidney tissues. CRT downregulated CD36 expression and activated the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway in DN rat kidney tissues. CRT intervention inhibited Hg-induced apoptosis and reversed autophagy in HK-2 cells. Moreover, overexpression of CD36 suppressed the beneficial effects of CRT. Conclusions: Our study is the first to report that CRT inhibited apoptosis and promoted autophagy in vivo and in vitro, which was achieved by reducing CD36 expression and activating the AMPK pathway. Therefore, CRT may be an effective drug to treat DN.

Arbuscular mycorrhizal fungi trigger danger-associated peptide signaling and inhibit carbon-phosphorus exchange with nonhost plants.

In soil, arbuscular mycorrhizal fungi (AMF) meet the roots of both host and presumed nonhost plants, but the interactional mechanisms of AMF with and functional relevance for nonhost plants is little known. Here we show AMF can colonize an individually grown nonhost plant, Arabidopsis thaliana, and suppress the growth of Arabidopsis and two nonhost Brassica crops. This inhibitory effect increased with increasing AMF inoculum density, and was independent of AMF species or nutrient availability. 13 C isotope labeling and physiological analyses revealed no significant carbon-phosphorus exchange between Arabidopsis and AMF, indicating a lack of nutritional function in this interaction. AMF colonization activated the danger-associated peptide Pep-PEPR signaling pathway, and caused clear defense responses in Arabidopsis. The impairment of Pep-PEPR signaling in nonhost plants greatly compromised AMF-triggered defensive responses and photosynthesis suppression, leading to higher colonization rates and reduced growth suppression upon AMF inoculation. Pretreatment with Pep peptide decreased AMF colonization, and largely substituted for AMF-induced growth suppression in nonhosts, confirming that the Pep-PEPR pathway is a key participant in resistance to AMF colonization and in mediating growth suppression of nonhost plants. This work greatly increases our knowledge about the functional relevance of AMF and their mechanisms of interactions with nonhost plants.

Peripheral blood mononuclear cell microRNAs are novel biomarkers for diagnosing and monitoring Crohn's disease.

Crohn's disease is a recurrent, progressive, immune-mediated inflammatory disease and merely manifests non-specific symptoms at early stage. In this study, we isolated peripheral blood mononuclear cells (PBMCs) to determine whether PBMC miRNAs are reliable biomarkers for Crohn's disease diagnosing and monitoring. 5 Crohn's disease patients and 5 healthy controls were recruited to find differentially expressed miRNAs by next generation sequencing. Candidate PBMC miRNAs were further validated by qRT-PCR in another cohort consisting of 86 Crohn's disease patients and 39 healthy controls. We found PBMC miR-582-5p could diagnose Crohn's disease with the area under receiver operating characteristic curve (AUROC) of 0.701(95%CI 0.606-0.796, p < .001). While PBMC miR-96-5p was significantly higher in active Crohn's disease and correlated with both clinical (ρ = 0.376, p < .001) and endoscopic activity (ρ = 0.512, p = .015). Furthermore, PBMC miR-96-5p had a better performance in recognizing active Crohn's disease with AUROC of 0.727 (95%CI 0.609-0.844, p = .001) than C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and fecal calprotectin. In conclusion, PBMC miR-582-5p may be further utilized as a diagnostic biomarker, while miR-96-5p may be a novel and valuable biomarker in monitoring disease activity.

LncRNA CASC15, MiR-23b Cluster and SMAD3 form a Novel Positive Feedback Loop to promote Epithelial-Mesenchymal Transition and Metastasis in Ovarian Cancer.

Cancer Susceptibility Candidate 15 (CASC15), which is a newly identified long noncoding RNA crucial for epigenetic regulation in human tumors, was found to be associated with poor prognosis of the patients with ovarian cancer by utilizing The Cancer Genome Atlas and Gene Expression Omnibus database. Therefore, the purpose of this paper was to explore the functional role and latent molecular mechanism of CASC15 in the progression of ovarian cancer. In vitro and in vivo experiments validated CASC15 as an oncogenic lncRNA in ovarian cancer, which could enhance metastasis through TGF-ß-induced epithelial-mesenchymal transition progress. MiR-23b-3p and miR-24-3p, which are members of the miR-23b cluster, were identified to directly target CASC15 through luciferase assays. Further mechanistic investigations indicated that CASC15-mediated miR-23b-3p/miR-24-3p sequestration cooperatively upregulated SMAD3 expression, which, in turn, would permit increased CASC15 mRNA level as a transcription activation factor. This study first described a miR-23b-3p/miR-24-3p-mediated positive feedback loop between CASC15 and SMAD3, which may reflect the underlying molecular mechanism of CASC15's oncogenic function in ovarian cancer.

Effect of perioperative nursing for artificial knee replacement on patients with osteosarcoma of the distal femur.

OBJECTIVE: To investigate the clinical application of perioperative nursing care for patients with osteosarcoma of the distal femur who received artificial knee replacement. METHODS: A total of 80 patients with osteosarcoma of the distal femur admitted to our hospital from March 2019 to March 2020 were selected as research subjects and divided into the control group and the study group according to their admission sequence. The control group was given routine nursing care, while the study group was given perioperative nursing care. The negative emotions, sleep quality, limb function, pain, complication rate, and nursing satisfaction of the two groups of patients after nursing care were analyzed. RESULTS: After nursing care, (1) the Hamilton depression rating scale (HAMD) and Hamilton anxiety scale (HAMA) scores of the study group were both lower than those of the control group; (2) the sleep quality score of the study group was lower than that of the control group (P < 0.001); (3) the study group obtained higher limb function score and excellent-and-good rate than the control group (P < 0.05); (4) the pain score of the study group was lower than that of the control group (P < 0.05), and the time to functional exercise and length of hospital stay of the study group were shorter than those of the control group (P < 0.05); (5) patients in the study group had a lower complication rate than those in the control group (P=0.02); (6) the nursing satisfaction rating of the study group was higher than that of the control group (P < 0.001). CONCLUSION: For patients with osteosarcoma of the distal femur treated by artificial knee replacement, in addition to the amelioration of negative emotions and sleep quality, perioperative nursing also improves the patients' limb function and satisfaction and mitigates pain and complications.

Low-dose mono(2-ethylhexyl) phthalate promotes ovarian cancer development through PPARα-dependent PI3K/Akt/NF-κB pathway.

The plasticizer di(2-ethylhexyl) phthalate (DEHP) and its hydrolysate mono(2-ethylhexyl) phthalate (MEHP) are major toxicants from plastics, but their association with hormone-dependent cancers has been controversial. We treated the human ovarian cancer cell lines SKOV3 and A2780 with low concentrations of DEHP/MEHP, and found that although no significant effect on cell proliferation was observed, ovarian cancer cell migration, invasion, and epithelial-mesenchymal transition (EMT) were promoted by submicromolar MEHP but not DEHP. Next, ovarian cancer patient data from The Cancer Genome Atlas (TCGA) were obtained and subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) supported enrichment and Kaplan-Meier survival analyses, which identified PI3K/Akt pathway as a pivotal signaling pathway in ovarian cancer. We found that 500 nM MEHP treatment significantly increased PIK3CA expression, which could be reversed by the knockdown of peroxisome proliferator-activated receptor alpha (PPARα). Silencing PIK3CA significantly suppressed the MEHP-induced migration, invasion and EMT. In addition, we validated that MEHP treatment promoted phosphorylation of Akt and degradation of IκB-α, thereby activating NF-κB and enhancing NF-κB nuclear translocation. In nude mice, MEHP exposure significantly promoted the metastasis of ovarian cancer xenografts, which could be suppressed by the treatment of PPARα inhibitor GW6471. Our findings showed that low-dose MEHP promoted ovarian cancer progression through activating PI3K/Akt/NF-κB pathway, in a PPARα-dependent manner.

The circular RNA circSlc7a11 promotes bone cancer pain pathogenesis in rats by modulating LLC-WRC 256 cell proliferation and apoptosis.

Treatment of bone cancer pain (BCP) caused by bone metastasis in advanced cancers remains a challenge in clinical oncology, and the underlying mechanisms of BCP are poorly understood. This study aimed to investigate the pathogenic roles of circular RNAs (circRNAs) in regulating cancer cell proliferation and BCP development. Eight differentially expressed circRNAs in the rat spinal cord were validated by agarose gel electrophoresis and Sanger sequencing. Expression of circRNAs and mRNAs was detected by quantitative RT-PCR. MTS assay and flow cytometry were performed to analyze cell proliferation and apoptosis, respectively. Differentially expressed mRNA profiles were characterized by deep RNA sequencing, hierarchical clustering, and functional categorization. The interactions among circRNAs, microRNAs (miRNAs), and mRNAs were predicted using TargetScan. Additionally, western blot was performed to determine the protein levels of Pax8, Isg15, and Cxcl10. Multiple circRNAs were differentially expressed in the spinal cords of BCP model rats; of these, circSlc7a11 showed the greatest increase in expression. The overexpression of circSlc7a11 significantly promoted cell proliferation and repressed apoptosis of LLC-WRC 256 and UMR-106 cells, whereas circSlc7a11 silencing produced the opposite effects. Altered expression of circSlc7a11 also induced substantial changes in the mRNA expression profiles of LLC-WRC 256 cells; these changes were linked to multiple apoptotic processes and signaling pathways, such as the chemokine signaling pathway, and formed a complex circRNA/miRNA/mRNA network. Additionally, Pax8, Isg15, and Cxc110 protein level in LLC-WRC 256 cells was consistent with the mRNA results. The circRNA circSlc7a11 regulates rat BCP development by modulating LLC-WRC 256 cell proliferation and apoptosis through multiple-signaling mechanisms.

Economic Burden and Health Care Access for Patients With Inflammatory Bowel Diseases in China: Web-Based Survey Study.

BACKGROUND: The increasing incidence of inflammatory bowel disease (IBD) has imposed heavy financial burdens for Chinese patients; however, data about their financial status and access to health care are still lacking. This information is important for informing patients with IBD about disease treatment budgets and health care strategies. OBJECTIVE: The aim of this study was to evaluate the economic status and medical care access of patients with IBD through the China Crohn's & Colitis Foundation web-based platform in China. METHODS: Our study was performed in 14 IBD centers in mainland China between 2018 and 2019 through WeChat. Participants were asked to complete a 64-item web-based questionnaire. Data were collected by the Wenjuanxing survey program. We mainly focused on income and insurance status, medical costs, and access to health care providers. Respondents were stratified by income and the associations of income with medical costs and emergency visit times were analyzed. RESULTS: In this study, 3000 patients with IBD, that is, 1922 patients with Crohn disease, 973 patients with ulcerative colitis, and 105 patients with undetermined colitis were included. During the last 12 months, the mean (SD) direct and indirect costs for per patient with IBD were approximately US $11,668.68 ($7944.44) and US $74.90 ($253.60) in China. The average reimbursement ratios for most outpatient and inpatient costs were less than 50%. However, the income of 85.5% (2565/3000) of the patients was less than ¥10,000 (US $1445) per month. Approximately 96.5% (2894/3000) of the patients were covered by health insurance, but only 24.7% (741/3000) of the patients had private commercial insurance, which has higher imbursement ratios. Nearly 98.0% (2954/3000) of the patients worried about their financial situation. Thus, 79.7% (2392/3000) of the patients with IBD tried to save money for health care and even delayed their medical treatments. About half of the respondents (1282/3000, 42.7%) had no primary care provider, and 52.2% (1567/3000) of the patients had to visit the emergency room 1-4 times per year for the treatment of their IBD. Multivariate analysis revealed that lower income (P=.001) and higher transportation (P=.004) and accommodation costs (P=.001) were significantly associated with the increased number of emergency visits of the patients. CONCLUSIONS: Chinese patients with IBD have enormous financial burdens and difficulties in accessing health care, which have increased their financial anxiety and inevitably influenced their disease outcomes. Early purchase of private insurance, thereby increasing the reimbursement ratio for medical expenses, and developing the use of telemedicine would be effective strategies for saving on health care costs.

Ticagrelor inhibits the NLRP3 inflammasome to protect against inflammatory disease independent of the P2Y12 signaling pathway.

Ticagrelor is the first reversibly binding oral P2Y12 receptor antagonist to inhibit platelet activation and has been approved by the Food and Drug Administration for the treatment of coronary artery disease. At present, the other pharmacological functions of ticagrelor remain poorly understood. The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome plays a critical role in the innate immune system, but its excessive activation also contributes to the pathogenesis of complex diseases. In this study, we systematically examined the effects of ticagrelor on the NLRP3 inflammasome and found that ticagrelor inhibits NLRP3 inflammasome activation in macrophages independent of its classic inhibitory effect on the P2Y12 signaling pathway. Further mechanistic studies demonstrate that ticagrelor attenuates the oligomerization of apoptosis-associated speck-like protein containing a CARD (ASC) by blocking chloride efflux, an effect achieved through the degradation of chloride intracellular channel proteins (CLICs) and blockade of the translocation of CLICs to the plasma membrane. Moreover, experiments on lipopolysaccharide-induced sepsis and alum-induced peritonitis in mice confirmed that ticagrelor mitigates the severity of systemic inflammation independent of P2Y12 receptor antagonism. Importantly, oral administration of ticagrelor rapidly and strongly inhibited NLRP3 inflammasome activation in peripheral blood mononuclear cells from patients with acute coronary syndrome. Overall, our study reveals a novel pharmacological function of ticagrelor in addition to its classic antiplatelet properties, which suggests that ticagrelor may serve as a potential therapeutic agent for use in NLRP3-associated diseases.

microRNA-524-5p inhibits proliferation and induces cell cycle arrest of osteosarcoma cells via targeting CDK6.

BACKGROUND: Osteosarcoma (OS) is one of the most commonly diagnosed malignant tumors that mainly affects children and adolescents. The underlying molecular mechanisms that are responsible for the initiation and development of OS are still not clear. Increasing evidence suggested the tumor suppressor role of microRNA-524-5p in a variety of cancers via targeting key pathways involved in tumorigenesis. The aim of this study was to characterize the function of miR-524-5p in OS. METHODS: A total 50 paired OS tissues and adjacent normal tissues were collected from OS patients. The expression of miR-524-5p in OS tissues and cells was detected by RT-qPCR. The CCK-8 assay, flow cytometry and transwell assay were applied to determine the proliferation and invasion abilities of OS cells. The targets of miR-524-5p were predicted using the miRDB dataset and confirmed by luciferase reporter assay and western blot analysis. RESULTS: The expression of miR-524-5p was decreased in OS tissues and cell lines. OS patients with lymph node metastasis harbored relative lower level of miR-524-5p. Overexpression of miR-524-5p in OS cells significantly suppressed the proliferation, drove cell cycle arrest and apoptosis. The mechanism investigation revealed that miR-524-5p bound the 3'-untranslated region (UTR) of Cyclin Dependent Kinase 6 (CDK6) and repressed the expression of CDK6 in OS cells. Overexpressed CDK6 was found in OS tissues, which was inversely correlated with that of miR-524-5p. Moreover, forced expression of CDK6 significantly reversed the anti-cancer effects of miR-524-5p on the proliferation, apoptosis and cell cycle arrest of OS cells. CONCLUSIONS: Our results identified the tumor-suppressive role of miR-524-5p in OS via targeting CDK6, which may lead to the identification of novel therapeutic target for the treatment of OS.

Assessing Oral Medication Adherence and Identifying Predictors of Low Adherence in Chinese Inflammatory Bowel Disease Patients.

BACKGROUND: Poor medication adherence in inflammatory bowel disease (IBD) had a negative impact on disease outcomes. In this study, we aimed to determine predictors of low adherence in the Chinese IBD populations and also aimed to compare a self-reported scale to a pharmacy refill index in assessing adherence of 5-ASA and azathioprine taken by Chinese IBD patients. PATIENTS AND METHODS: Adult patients with IBD who had been taking 5-ASA or azathioprine for at least 3 months were recruited from hospital outpatient clinics. The MPR was calculated from previous six-month pharmacy refill data and the self-reported Morisky Medication Adherence Scale (MMAS-8) was issued through QR code questionnaires. Intentional and unintentional adherence scores were calculated according to specific items. Non-adherence was defined as MMAS-8 scores <6 or MPR < 0.8. RESULTS: The response rate in the IBD patients was as high as 97%. 5-ASA non-adherence rate assessed by MPR was 30% and 37% by MMAS-8, and azathioprine non-adherence rate assessed was 33% by both MPR and MMAS-8. In a linear regression analysis, MPR value was significantly correlated with MMAS-8 score in 5-ASA group (r=0.4, p=0.003), and significantly correlated with unintentional adherence score (r=0.47, p<0.001). No significant correlation was observed between MPR value and MMAS-8 score in azathioprine group. Multivariate analysis demonstrated that age (OR: 1.08; 95% CI: 1.02-1.13; P=0.0015) and previous abdominal surgery (OR: 3.18; 95% CI: 2.09-4.27; P=0.04) were associated with high medication adherence. While patients who had small intestine lesion (OR: 0.09; 95% CI: 0.01-0.17; P=0.006) were associated with low adherence. CONCLUSION: Predictors of low adherence were young age, lesions on small intestine, whereas previous abdominal surgery was a protective factor. This study also demonstrated that the MMAS-8 scale was a valid instrument for assessing 5-ASA adherence in IBD patients. Unintentional non-adherence was significantly related to the total non-adherence, which would allow to use the tool to seek ways for adherence improvement.

circStrn3 is involved in bone cancer pain regulation in a rat model.

Bone cancer pain (BCP) is a common chronic pain that is caused by a primary or metastatic bone tumor. More detailed molecular mechanisms of BCP are warranted. In this study, we established a BCP rat model. The von Frey hair test, body weight, and hematoxylin and eosin staining were employed. We screened differentially expressed circRNAs (DECs) between the BCP group and sham group. The results revealed that 850 DECs were significantly up-regulated and 644 DECs were significantly down-regulated in the BCP group. Furthermore, we identified 1177 differentially expressed genes (DEGs) significantly up-regulated and 565 DEGs significantly down-regulated in the BCP group. Gene Ontology annotation of all 1742 DEGs revealed that biological regulation of metabolic processes, cellular processes, and binding were the top enriched terms. For Kyoto Encyclopedia of Genes and Genomes analysis, phagosome, HTLV-I infection, proteoglycans in cancer, and herpes simplex infection were significantly enriched in this study. In addition, we identified four selected circRNAs, chr6:72418120|72430205, chr20:7561057|7573740, chr18:69943105|69944476, and chr5:167516581|167558250, by quantitative real time PCR. chr6:72418120|72430205 (circStrn3) was selected for further study based on expression level and the circRNA-miRNA-mRNA network table. Western blot analysis suggested that knockdown of circStrn3 could effectively induce Walker 256 cell apoptosis. In summary, our study provided a more in-depth understanding of the molecular mechanisms of BCP.

Benzo(a)pyrene regulated A549 cell migration, invasion and epithelial-mesenchymal transition by up-regulating long non-coding RNA linc00673.

As a major toxicant which is abundant in tobacco smoking, benzo(a)pyrene (BaP) is considered as a strong carcinogen of lung cancer. In spite of the intensive research, the role that BaP plays in lung cancer still lacks a comprehensive and precise understanding. Recently, a long non-coding RNA, linc00673, has emerged as a central player in different kinds of malignancies, including non-small cell lung cancer (NSCLC). In the present study, we found that BaP with the concentration of no more than 8 µM did not affect cell proliferation in the NSCLC cell line A549, while it significantly enhanced A549 cell migration and invasion. Further results revealed that BaP promoted mesenchymal biomarkers expression and inhibited the major epithelial biomarker E-cadherin in a time and dose dependent manner, which indicated epithelial-mesenchymal transition (EMT) was induced by BaP in A549 cells. Through quantitative real-time PCR, we observed that BaP significantly elevated the expression level of linc00673. While after the knockdown of aryl hydrocarbon receptor (AHR), the up-regulating effect of BaP on linc00673 was reversed. Furthermore, silencing linc00673 significantly suppressed the BaP-induced migration, invasion, and EMT in A549 cells. In summary, our study demonstrates that BaP promotes A549 cell migration, invasion and EMT through up-regulating the expression of linc00673 in an AHR-dependent manner.

microRNA-329 reduces bone cancer pain through the LPAR1-dependent LPAR1/ERK signal transduction pathway in mice.

BACKGROUND: Bone cancer pain (BCP) is a common symptom occurring among patients with cancer and has a detrimental effect on their quality of life. Growing evidence has implicated microRNA-329 (miR-329) in the progression of bone diseases. In the present study, we aimed to elucidate the potential effects of miR-329 on BCP in a BCP mouse model via binding to lysophosphatidic acid receptor 1 (LPAR1) through the LPAR1/extracellular signal-regulated kinase (ERK) signaling pathway. METHODS: Initially, a BCP mouse model was established via injection of 4 × 104 murine breast tumor (4T1 cell) cells (4 µl). The interaction between miR-329 and LPAR1 was identified using a bioinformatics website and dual luciferase reporter gene assay. The modeled mice were subsequently treated with miR-329 mimic, LPAR1 shRNA, or both, in order to examine the effect of miR-329 on the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) of mice, the expression of LPAR1/ERK signaling pathway-related genes. RESULTS: The positive expression rate of LPAR1 protein and extent of ERK1/2 phosphorylation were increased in BCP mouse models. LPAR1 is a target gene of miR-329, which can inhibit the expression of LPAR1. In response to miR-329 overexpression and LPAR1 silencing, BCP mice showed increased PWT and PWL, along with decreased LPAR1 expression and ratio of p-ERK/ERK. CONCLUSIONS: Altogether, the results obtained indicated that miR-329 can potentially alleviate BCP in mice via the inhibition of LPAR1 and blockade of the LPAR1/ERK signaling pathway, highlighting that upregulation of miR-329 could serve as a therapeutic target for BCP treatment.