Circulating microRNAs: A Potential Role in Diagnosis and Prognosis of Acute Myocardial Infarction

Rapid and correct diagnosis of acute myocardial infarction (AMI) plays a crucial role in saving patients' life. Although some biomarkers (such as cardiac troponin and creatine kinase) are available for AMI diagnosis so far, there is still a clinical need for novel biomarkers, which can reliably rule in or rule out AMI immediately on admission. Circulating microRNAs (miRNAs) are a potential choice for novel biomarkers in AMI diagnosis and prognosis with high sensitivity and specificity. Circulating microRNAs are endogenous miRNAs that are detectable in whole blood, serum, or plasma in a highly stable form. Until now, around 20 circulating miRNAs were reported to be closely associated with AMI. In this minireview, we summarized recent available data on the correlation between circulating miRNAs and AMI. Some miRNAs, such as miR-208, miR-499, miR-133, and miR-1, were given special attention, since they may have a potential prospect in diagnosis and prognosis of AMI

Radio Plateaus in Gamma-Ray Burst Afterglows and Their Application in Cosmology

The plateau phase in the radio afterglows has been observed in very few gamma-ray bursts (GRBs), and 27 radio light curves with plateau phase were acquired from the published literature in this article. We obtain the related parameters of the radio plateau, such as temporal indexes during the plateau phase ($\alpha_1$ and $\alpha_2$), break time (\Tbz) and the corresponding radio flux ($F_{\rm b}$). The two parameter Dainotti relation between the break time of the plateau and the corresponding break luminosity (\Lbz) in radio band is \Lbz \propto \Tbz^{-1.20\pm0.24}. Including the isotropic energy \Eiso and the peak energy \Epi, the three parameter correlations for the radio plateaus are written as \Lbz \propto \Tbz^{-1.01 \pm 0.24} \Eiso^{0.18 \pm 0.09} and \Lbz \propto \Tbz^{-1.18 \pm 0.27} \Epi^{0.05 \pm 0.28}, respectively. The correlations are less consistent with that of X-ray and optical plateaus, implying that radio plateaus may have a different physical mechanism. The typical frequencies crossing the observational band may be a reasonable hypothesis that causes the breaks of the radio afterglows. We calibrate GRBs empirical luminosity correlations as standard candle for constraining cosmological parameters, and find that our samples can constrain the flat $\Lambda$CDM model well, while are not sensitive to non-flat ${\Lambda}$CDM model. By combining GRBs with other probes, such as SN and CMB, the constraints on cosmological parameters are \om = 0.297\pm0.006 for the flat ${\Lambda}$CDM model and \om = 0.283\pm0.008, \oL = 0.711\pm0.006 for the non-flat ${\Lambda}$CDM model, respectively.Comment: 16 pages, 6 figures and 6 tables, accepted for publication in Ap

Safety and Technical Feasibility of Sustainable Reuse of Shale Gas Flowback and Produced Water after Advanced Treatment Aimed at Wheat Irrigation

Treatment and reuse of flowback and produced water (FPW) from shale gas extraction for agricultural irrigation has often been proposed as a sustainable alternative to disposal via deep-well injection. Here, we investigate the effects of FPW on the germination period, macroscopic growth, element enrichment, and grain gene expression of wheat upon dilution and advanced membrane treatment of the liquid stream. Compared to tap water, irrigation with treated FPW shortened the germination time, slightly improved the seed vigor index, and ensured a similar germination rate. On the other hand, the biomass and grain yield of mature wheat irrigated with treated FPW and with FPW diluted to 5% groups decreased compared to tests using tap water. After a whole growth cycle of wheat, higher concentrations of nutrients, such as K, Ca, and Mg were enriched in mature wheat tissue irrigated with treated FPW. However, the Pb and Cr contents of mature wheat grains treated with three types of irrigation waters exceeded the standard to varying degrees. A total of 1973 differentially expressed genes were mainly related to binding, catalytic activity, cellular process, metabolic process, and cell part, more than half of which were upregulated and induced by irrigation with treated FPW. These findings provide critical guidance for the reuse of treated shale gas FPW for agricultural application from the perspective of plant uptake of toxic elements, as well as crop and human health risks

Calcium-sensing receptors regulate cardiomyocyte Ca2+ signaling via the sarcoplasmic reticulum-mitochondrion interface during hypoxia/reoxygenation

Communication between the SR (sarcoplasmic reticulum, SR) and mitochondria is important for cell survival and apoptosis. The SR supplies Ca2+ directly to mitochondria via inositol 1,4,5-trisphosphate receptors (IP3Rs) at close contacts between the two organelles referred to as mitochondrion-associated ER membrane (MAM). Although it has been demonstrated that CaR (calcium sensing receptor) activation is involved in intracellular calcium overload during hypoxia/reoxygenation (H/Re), the role of CaR activation in the cardiomyocyte apoptotic pathway remains unclear. We postulated that CaR activation plays a role in the regulation of SR-mitochondrial inter-organelle Ca2+ signaling, causing apoptosis during H/Re. To investigate the above hypothesis, cultured cardiomyocytes were subjected to H/Re. We examined the distribution of IP3Rs in cardiomyocytes via immunofluorescence and Western blotting and found that type 3 IP3Rs were located in the SR. [Ca2+]i, [Ca2+]m and [Ca2+]SR were determined using Fluo-4, x-rhod-1 and Fluo 5N, respectively, and the mitochondrial membrane potential was detected with JC-1 during reoxygenation using laser confocal microscopy. We found that activation of CaR reduced [Ca2+]SR, increased [Ca2+]i and [Ca2+]m and decreased the mitochondrial membrane potential during reoxygenation. We found that the activation of CaR caused the cleavage of BAP31, thus generating the pro-apoptotic p20 fragment, which induced the release of cytochrome c from mitochondria and the translocation of bak/bax to mitochondria. Taken together, these results reveal that CaR activation causes Ca2+ release from the SR into the mitochondria through IP3Rs and induces cardiomyocyte apoptosis during hypoxia/reoxygenation

Acupuncture for menstruation-related migraine prophylaxis:A multicenter randomized controlled trial

OBJECTIVE: The aim of this study was to evaluate the efficacy of acupuncture, an alternative medicine therapy, as a preventive treatment for menstruation-related migraine (MRM). PATIENTS AND METHODS: This was a prospective, multicenter, double-dummy, participant-blinded, randomized controlled clinical trial conducted in China between 1 April 2013, and 30 April 2014. The participants were enrolled from four study centers and randomized to into either the acupuncture group, which received 24 sessions of acupuncture at traditional acupoints plus placebo, or the medication group, which received sham acupuncture plus naproxen. The primary endpoint was change from the baseline average number of migraine days per perimenstrual period over cycles 1−3. The secondary endpoints included changes from the baseline average number of migraine days outside the perimenstrual period, mean number of migraine hours during and outside the perimenstrual period, mean visual analog scale score during and outside the perimenstrual period, ≥50% migraine responder rate, and the proportion of participants who used acute pain medication over cycles 1−3 and 4−6. RESULTS: A total of 172 women with MRM were enrolled; 170 in the intention-to-treat analyses. Our primary outcome reported a significant between-group difference that favored the acupuncture group (95% CI, 0.17–0.50; P < 0.001), with the average reduction of migraine days per perimenstrual period from the baseline was 0.94 (95% CI, 0.82–1.07) in the acupuncture group and 0.61 (95% CI, 0.50–0.71) in the medication group over cycles 1−3. CONCLUSION: This study showed that compared to medication, acupuncture reduces the number of migraine days experienced by patients with MRM. For patients who received the acupuncture treatment over three cycles, the preventive effect of the therapy was sustained for six cycles. CLINICAL TRIAL REGISTRATION: [https://www.isrctn.com/ISRCTN57133712], identifier [ISRCTN15663606]

The combination of hand grip strength and modified Glasgow prognostic score predicts clinical outcomes in patients with liver cancer

PurposePrevious studies have shown that both hand grip strength (HGS) and the modified Glasgow Prognostic Score (mGPS) are associated with poor clinical outcomes in patients with liver cancer. In spite of this, no relevant studies have been conducted to determine whether the combination of HGS and mGPS can predict the prognosis of patients with liver cancer. Accordingly, this study sought to explore this possibility.MethodsThis was a multicenter study of patients with liver cancer. Based on the optimal HGS cutoff value for each sex, we determined the HGS cutoff values. The patients were divided into high and low HGS groups based on their HGS scores. An mGPS of 0 was defined as low mGPS, whereas scores higher than 0 were defined as high mGPS. The patients were combined into HGS-mGPS groups for the prediction of survival. Survival analysis was performed using Kaplan–Meier curves. A Cox regression model was designed and adjusted for confounders. To evaluate the nomogram model, receiver operating characteristic curves and calibration curves were used.ResultsA total of 504 patients were enrolled in this study. Of these, 386 (76.6%) were men (mean [SD] age, 56.63 [12.06] years). Multivariate analysis revealed that patients with low HGS and high mGPS had a higher risk of death than those with neither low HGS nor high mGPS (hazard ratio [HR],1.50; 95% confidence interval [CI],1.14–1.98; p = 0.001 and HR, 1.55; 95% CI, 1.14–2.12, p = 0.001 respectively). Patients with both low HGS and high mGPS had 2.35-fold increased risk of death (HR, 2.35; 95% CI, 1.52–3.63; p &lt; 0.001). The area under the curve of HGS-mGPS was 0.623. The calibration curve demonstrated the validity of the HGS-mGPS nomogram model for predicting the survival of patients with liver cancer.ConclusionA combination of low HGS and high mGPS is associated with poor prognosis in patients with liver cancer. The combination of HGS and mGPS can predict the prognosis of liver cancer more accurately than HGS or mGPS alone. The nomogram model developed in this study can effectively predict the survival outcomes of liver cancer

A novel prognostic scoring model based on copper homeostasis and cuproptosis which indicates changes in tumor microenvironment and affects treatment response

Background: Intracellular copper homeostasis requires a complex system. It has shown considerable prospects for intervening in the tumor microenvironment (TME) by regulating copper homeostasis and provoking cuproptosis. Their relationship with hepatocellular carcinoma (HCC) remains elusive.Methods: In TCGA and ICGC datasets, LASSO and multivariate Cox regression were applied to obtain the signature on the basis of genes associated with copper homeostasis and cuproptosis. Bioinformatic tools were utilized to reveal if the signature was correlated with HCC characteristics. Single-cell RNA sequencing data analysis identified differences in tumor and T cells’ pathway activity and intercellular communication of immune-related cells. Real-time qPCR analysis was conducted to measure the genes’ expression in HCC and adjacent normal tissue from 21 patients. CCK8 assay, scratch assay, transwell, and colony formation were conducted to reveal the effect of genes on in vitro cell proliferation, invasion, migration, and colony formation.Results: We constructed a five-gene scoring system in relation to copper homeostasis and cuproptosis. The high-risk score indicated poor clinical prognosis, enhanced tumor malignancy, and immune-suppressive tumor microenvironment. The T cell activity was markedly reduced in high-risk single-cell samples. The high-risk HCC patients had a better expectation of ICB response and reactivity to anti-PD-1 therapy. A total of 156 drugs were identified as potential signature-related drugs for HCC treatment, and most were sensitive to high-risk patients. Novel ligand-receptor pairs such as FASLG, CCL, CD40, IL2, and IFN-Ⅱ signaling pathways were revealed as cellular communication bridges, which may cause differences in TME and immune function. All crucial genes were differentially expressed between HCC and paired adjacent normal tissue. Model-constructed genes affected the phosphorylation of mTOR and AKT in both Huh7 and Hep3B cells. Knockdown of ZCRB1 impaired the proliferation, invasion, migration, and colony formation in HCC cell lines.Conclusion: We obtained a prognostic scoring system to forecast the TME changes and assist in choosing therapy strategies for HCC patients. In this study, we combined copper homeostasis and cuproptosis to show the overall potential risk of copper-related biological processes in HCC for the first time

Association between C-reactive protein-albumin-lymphocyte (CALLY) index and overall survival in patients with colorectal cancer: From the investigation on nutrition status and clinical outcome of common cancers study

BackgroundColorectal cancer (CRC) is among the most common malignant cancers worldwide, and its development is influenced by inflammation, nutrition, and the immune status. Therefore, we combined C-reactive protein (CRP), albumin, and lymphocyte, which could reflect above status, to be the CRP-albumin-lymphocyte (CALLY) index, and evaluated its association with overall survival (OS) in patients with CRC.MethodsThe clinicopathological and laboratory characteristics of 1260 patients with CRC were collected from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) study. Cox regression analysis was performed to assess the association between the CALLY index and OS. A nomogram including sex, age, the CALLY index and TNM stage was constructed. The Concordance Index (C-index) was utilized to evaluate the prognostic value of the CALLY index and classical CRC prognostic factors, such as modified Glasgow prognostic score (mGPS), neutrocyte to lymphocyte ratio (NLR), systemic immune inflammation index (SII), and platelet to lymphocyte ratio (PLR), as well as to assess the prognostic value of the nomogram and TNM stage.ResultsMultivariate Cox regression analyses demonstrated that the CALLY index was independently associated with OS in patients with CRC [Hazard ratio (HR) = 0.91, 95% confidence interval (CI) = 0.87-0.95, P&lt;0.001]. The CALLY index showed the highest prognostic value (C-index = 0.666, 95% CI = 0.638-0.694, P&lt;0.001), followed by mGPS, NLR, SII, and PLR. The nomogram demonstrated higher prognostic value (C-index = 0.784, 95% CI = 0.762-0.807, P&lt;0.001) than the TNM stage.ConclusionThe CALLY index was independently associated with OS in patients with CRC and showed higher prognostic value than classical CRC prognostic factors. The nomogram could provide more accurate prognostic prediction than TNM stage

Genetic Regulation of the Thymic Stromal Lymphopoietin (TSLP)/TSLP Receptor (TSLPR) Gene Expression and Influence of Epistatic Interactions Between IL-33 and the TSLP/TSLPR Axis on Risk of Coronary Artery Disease

The thymic stromal lymphopoietin (TSLP)/TSLP receptor (TSLPR) axis is involved in multiple inflammatory immune diseases, including coronary artery disease (CAD). To explore the causal relationship between this axis and CAD, we performed a three-stage case-control association analysis with 3,628 CAD cases and 3,776 controls using common variants in the genes TSLP, interleukin 7 receptor (IL7R), and TSLPR. Three common variants in the TSLP/TSLPR axis were significantly associated with CAD in a Chinese Han population [rs3806933T in TSLP, Padj = 4.35 × 10−5, odds ratio (OR) = 1.18; rs6897932T in IL7R, Padj = 1.13 × 10−7, OR = 1.31; g.19646A&gt;GA in TSLPR, Padj = 2.04 × 10−6, OR = 1.20]. Reporter gene analysis demonstrated that rs3806933 and rs6897932 could influence TSLP and IL7R expression, respectively. Furthermore, the “T” allele of rs3806933 might increase plasma TSLP levels (R2 = 0.175, P &lt; 0.01). In a stepwise procedure, the risk for CAD increased by nearly fivefold compared with the maximum effect of any single variant (Padj = 6.99 × 10−4, OR = 4.85). In addition, the epistatic interaction between TSLP and IL33 produced a nearly threefold increase in the risk of CAD in the combined model of rs3806933TT-rs7025417TT (Padj = 3.67 × 10−4, OR = 2.98). Our study illustrates that the TSLP/TSLPR axis might be involved in the pathogenesis of CAD through upregulation of mRNA or protein expression of the referenced genes and might have additive effects on the CAD risk when combined with IL-33 signaling