Edited by Laszlo NagyKeywords: MicroRNA MiR-26 LXR Cholesterol efflux ABCA1 ARL7 a b s t r a c t Cellular cholesterol levels are tightly regulated and represent a balance of cholesterol uptake, endogenous synthesis and efflux. Although the classic transcriptional regulations of cholesterol metabolism by liver X receptors (LXRs) have been well studied, the potential effects of LXRresponsive microRNAs (miRNAs) still need to be unveiled. Here, we describe that miR-26, an LXR-suppressed miRNA, inhibits the expression of the ATP-binding cassette transporter A1 (ABCA1) and ADP-ribosylation factor-like 7 (ARL7), two LXR target genes which play critical roles in cholesterol efflux. These findings have not only figured out an alternative mechanism for LXR regulation, but also provided a potential therapeutic target for cholesterol metabolic disorders.

Periostin (POSTN) secreted by intrahepatic cholangiocarcinoma stem cells (ICSCs) serves important roles in promoting tumor progression. The present study aimed to investigate POSTN-recruited tumor-associated macrophages (TAMs) in intrahepatic cholangiocarcinoma (ICC). A total of 50 cases were used to investigate the distribution of ICSCs and TAMs in ICC. HCCC-9810 cells were sorted by cluster of differentiation (CD)44, the expression of POSTN of CD44 (cancer stem cells) and CD44 cells (non-cancer stem cells), and medium were evaluated by western blot analysis. HCCC-9810 cells and THP-1 macrophages were used to detect the effects of POSTN on recruiting TAMs . The present study revealed that CD44 cells in ICC tissues and the HCCC-9810 cell line were associated with high POSTN secretion levels. Furthermore, POSTN was associated with TAM density in primary ICC tissues. Additionally, POSTN increased the migration of TAMs derived from THP-1 cells. These findings suggested that POSTN secreted by ICSCs may serve important functions in TAM recruitment, and it may be a potential curative strategy to target the tumor microenvironment in ICC.

Background/Aims: To examine the cross-sectional and longitudinal associations of serum ferritin levels with hyperuricemia. Methods: A cross-sectional and subsequently prospective study was performed among the employees of Zhenhai Refining and Chemical Company, Ningbo, China. In a cross-sectional study, the association between serum ferritin levels and the prevalence of hyperuricemia was analyzed. Subjects who were free of hyperuricemia at baseline were followed up annually to explore the prospective association between serum ferritin levels and hyperuricemia incidence. Results: Of the 10,074 subjects enrolled at baseline, 1,731 (17.18%) fulfilled the diagnostic criteria of hyperuricemia. Subjects with hyperuricemia presented significantly higher serum ferritin levels, and the levels were positively correlated with the prevalence of hyperuricemia. During a total of 22,367 person-years of follow-up, 502 subjects developed hyperuricemia. The overall incidence of hyperuricemia for 1,000 person-years of follow-up was 22.4, ranging from 17.6 in subjects with baseline serum ferritin levels in the first quintile to 19.2, 21.7, 23.9, and 30.7 in subjects in quintiles 2, 3, 4, and 5, respectively (p for trend < 0.001). Cox regression analyses showed that serum ferritin levels were positively associated with the risk of incident hyperuricemia. Conclusions: Our cross-sectional and longitudinal results indicate that high serum ferritin levels increase the risk of hyperuricemia.

Background The role of miR-26a-5p expression in cardiac hypertrophy remains unclear. Herein, the effect of miR-26a-5p on cardiac hypertrophy was investigated using phenylephrine (PE)-induced cardiac hypertrophy in vitro and in a rat model of hypertension-induced hypertrophy in vivo. Methods The PE-induced cardiac hypertrophy models in vitro and vivo were established. To investigate the effect of miR-26a-5p activation on autophagy, the protein expression of autophagosome marker (LC3) and p62 was detected by western blot analysis. To explore the effect of miR-26a-5p activation on cardiac hypertrophy, the relative mRNA expression of cardiac hypertrophy related mark GSK3β was detected by qRT-PCR in vitro and vivo. In addition, immunofluorescence staining was used to detect cardiac hypertrophy related mark α-actinin. The cell surface area was measured by immunofluorescence staining. The direct target relationship between miR-26a-5p and GSK3β was confirmed by dual luciferase report. Results MiR-26a-5p was highly expressed in PE-induced cardiac hypertrophy. MiR-26a-5p promoted LC3II and decreased p62 expression in PE-induced cardiac hypertrophy in the presence or absence of lysosomal inhibitor. Furthermore, miR-26a-5p significantly inhibited GSK3β expression in vitro and in vivo. Dual luciferase report results confirmed that miR-26a-5p could directly target GSK3β. GSK3β overexpression significantly reversed the expression of cardiac hypertrophy-related markers including ANP, ACTA1 and MYH7. Immunofluorescence staining results demonstrated that miR-26a-5p promoted cardiac hypertrophy related protein α-actinin expression, and increased cell surface area in vitro and in vivo. Conclusion Our study revealed that miR-26a-5p promotes myocardial cell autophagy activation and cardiac hypertrophy by regulating GSK3β, which needs further research.

Beta thalassemia is a hereditary disorder resulted from mutations in the β globin gene leading to alpha/beta imbalance, ineffective erythropoiesis, and chronic anemia. Three types have been defined, based on the degree of reduced beta-globin chain synthesis and clinical phenotype: major, intermedia and minor (heterozygote carrier state). Beta thalassemia intermedia is characterized by heterogeneity for the wide clinical spectrum of various genotypes and a wide range of presentations. The genotypes of beta thalassemia intermedia are much complicated referring to β+/β+,β+/β0, Hb E/β0, β0/β0 compounding alpha thalassemia and so on. In this present case, we reported a rare beta thalassemia intermedia genotype of double heterozygosity for poly A (A>G) and CD17(A>T) indicated of β+/β0 in a Chinese family.

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Previous studies showed a controversial result on the relationship between probiotics treatment duration and blood pressure (BP). The present meta‐analysis is performed to summarize the effects of long‐term (≥8 weeks) use of probiotics on office and ambulatory BP using combined evidence from randomized, controlled trials. We searched PubMed, Embase, Cochrane library, and the http://clinicaltrials.gov till January, 2021 to identify eligible articles. Primary outcomes were changes in office BP. In the presence of heterogeneity, a random‐effects model was used to calculate the combined treatment effect. Begg's funnel plots and Egger's regression test were used to assess the publication bias. Meta‐analysis of 26 trials in 1624 participants demonstrated that probiotic consumption significantly decreased office systolic BP by 2.18 mmHg (95% confidence interval [CI], −3.41 to −0.94 mmHg) and diastolic BP by 1.07 mmHg (95% CI, −1.72 to −0.41 mmHg). The analysis on ambulatory BP from three trials showed a similar reduction by −2.35/−1.61 mmHg (p ≤ .052). Subgroup analysis in hypertensive and diabetic patients showed a significant reduction in systolic and diastolic BP (p ≤ .02). The reductions in diabetic and hypertensive patients were comparatively larger than nondiabetic and normotensive patients (p ≥ .052). With the increase of age, baseline body mass index (BMI), treatment duration, and systolic BP, the effects of probiotics on BP did not increase significantly (ptrend ≥ .18). The present meta‐analysis suggests a beneficial effect of probiotics on BP by a modest degree, especially in the diabetes mellitus and hypertension. Prolonging the treatment duration could not improve the antihypertensive effect.

Background. Obstructive sleep apnea (OSA) is common in patients with hypertension. Nonetheless, OSA is underdiagnosed despite considerable evidence of the association between OSA and adverse health outcomes. This study developed and validated a clinical nomogram to predict OSA in patients with hypertension based on the Epworth Sleepiness Scale (ESS) score and OSA-related parameters. Methods. A total of 347 hypertensive patients with suspected OSA were retrospectively enrolled and randomly assigned to a training set and a validation set at 70 : 30 (N = 242/N = 105) ratio. OSA was diagnosed through sleep monitoring and was defined as an apnea-hypopnea index ≥5 events/h. Using the least absolute shrinkage and selection operator regression model, we identified potential predictors of OSA and constructed a nomogram model in the training set. The predictive performance of the nomogram was assessed and validated by discrimination and calibration. The nomogram was also compared with ESS scores according to decision curve analysis (DCA), integrated discrimination index (IDI), and net reclassification index (NRI). Results. ESS scores, body mass index, neck circumference, snoring, and observed apnea predicted OSA are considered. The nomogram showed similar discrimination between the training set (AUC: 0.799, 95% CI: 0.743–0.847) and validation set (AUC: 0.766, 95% CI: 0.673–0.843) and good calibration in the training ( P = 0.925 > 0.05 ) and validation ( P = 0.906 > 0.05 ) sets. Compared with the predictive value of the ESS, the nomogram was clinically useful and significantly improved reclassification accuracy (NRI: 0.552, 95% CI: 0.282–0.822, P < 0.001 ; IDI: 0.088, 95% CI: 0.045–0.133, P < 0.001 ) at a probability threshold of >42%. Conclusions. We developed a novel OSA prediction nomogram based on ESS scores and OSA-related parameters. This nomogram may help improve clinical decision-making, especially in communities and primary clinics, where polysomnography is unavailable.