Curcumin suppresses colorectal cancer by induction of ferroptosis via regulation of p53 and solute carrier family 7 member 11/glutathione/glutathione peroxidase 4 signaling axis.

Driven by iron-dependent lipid peroxidation, ferroptosis is regulated by p53 and solute carrier family 7 member 11 (SLC7A11)/glutathione/glutathione peroxidase 4 (GPX4) axis in colorectal cancer (CRC). This study aimed to investigate the influence of curcumin (CUR) on ferroptosis in CRC. The efficacies of CUR on the malignant phenotype of CRC cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, wound healing, and clonogenic assays. The effects of CUR on ferroptosis of CRC cells were evaluated by transmission electron microscopy, lactate dehydrogenase release assay, Fe2+ staining, and analyses of reactive oxygen species, lipid peroxide, malondialdehyde, and glutathione levels. CUR's targets in ferroptosis were predicted by network pharmacological study and molecular docking. With SW620 xenograft tumors, the efficacy of CUR on CRC was investigated, and the effects of CUR on ferroptosis were assessed by detection of Fe2+, malondialdehyde, and glutathione levels. The effects of CUR on expressions of p53, SLC7A11, and GPX4 in CRC cells and tumors were analyzed by quantitative reverse transcription-polymerase chain reaction, western blotting, and immunohistochemistry. CUR suppressed the proliferation, migration, and clonogenesis of CRC cells and xenograft tumor growth by causing ferroptosis, with enhanced lactate dehydrogenase release and Fe2+, reactive oxygen species, lipid peroxide, and malondialdehyde levels, but attenuated glutathione level in CRC. In silico study indicated that CUR may bind p53, SLC7A11, and GPX4, consolidated by that CUR heightened p53 but attenuated SLC7A11 and GPX4 mRNA and protein levels in CRC. CUR may exert an inhibitory effect on CRC by inducing ferroptosis via regulation of p53 and SLC7A11/glutathione/GPX4 axis.

Armeniacae semen amarum: a review on its botany, phytochemistry, pharmacology, clinical application, toxicology and pharmacokinetics.

Armeniacae semen amarum-seeds of Prunus armeniaca L. (Rosaceae) (ASA), also known as Kuxingren in Chinese, is a traditional Chinese herbal drug commonly used for lung disease and intestinal disorders. It has long been used to treat coughs and asthma, as well as to lubricate the colon and reduce constipation. ASA refers to the dried ripe seed of diverse species of Rosaceae and contains a variety of phytochemical components, including glycosides, organic acids, amino acids, flavonoids, terpenes, phytosterols, phenylpropanoids, and other components. Extensive data shows that ASA exhibits various pharmacological activities, such as anticancer activity, anti-oxidation, antimicrobial activity, anti-inflammation, protection of cardiovascular, neural, respiratory and digestive systems, antidiabetic effects, and protection of the liver and kidney, and other activities. In clinical practice, ASA can be used as a single drug or in combination with other traditional Chinese medicines, forming ASA-containing formulas, to treat various afflictions. However, it is important to consider the potential adverse reactions and pharmacokinetic properties of ASA during its clinical use. Overall, with various bioactive components, diversified pharmacological actions and potent efficacies, ASA is a promising drug that merits in-depth study on its functional mechanisms to facilitate its clinical application.

Qinhuo Shanggan oral solution resolves acute lung injury by down-regulating TLR4/NF-κB signaling cascade and inhibiting NLRP3 inflammasome activation.

Acute lung injury (ALI) is a common condition, particularly in the COVID-19 pandemic, which is distinguished by sudden onset of respiratory insufficiency with tachypnea, oxygen-refractory cyanosis, reduced lung compliance and diffuse infiltration of pulmonary alveoli. It is well-established that increasing activity of toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling axis and the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation are associated with the pathogenesis of ALI. Since ALI poses a huge challenge to human health, it is urgent to tackle this affliction with therapeutic intervention. Qinhuo Shanggan oral solution (QHSG), a traditional Chinese herbal formula, is clinically used for effective medication of various lung diseases including ALI, with the action mechanism obscure. In the present study, with the rat model of lipopolysaccharide (LPS)-induced ALI, QHSG was unveiled to ameliorate ALI by alleviating the pathological features, reversing the alteration in white blood cell profile and impeding the production of inflammatory cytokines through down-regulation of TLR4/NF-κB signaling cascade and inhibition of NLRP3 inflammasome activation. In LPS-stimulated RAW264.7 mouse macrophages, QHSG was discovered to hinder the generation of inflammatory cytokines by lessening TLR4/NF-κB signaling pathway activity and weakening NLRP3 inflammasome activation. Taken together, QHSG may resolve acute lung injury, attributed to its anti-inflammation and immunoregulation by attenuation of TLR4/NF-κB signaling cascade and inhibition of NLRP3 inflammasome activation. Our findings provide a novel insight into the action mechanism of QHSG and lay a mechanistic foundation for therapeutic intervention in acute lung injury with QHSG in clinical practice.

Berberine is a suppressor of Hedgehog signaling cascade in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a malignant affliction that burdens people globally. Overactivated Hedgehog signal is highly implicated in CRC pathogenesis. Phytochemical berberine exerts strong potency on CRC, with molecular mechanism elusive. PURPOSE: We sought to study berberine's anti-CRC action and explore its underlying mechanism based on Hedgehog signaling cascade. METHODS: In CRC HCT116 cells and SW480 cells treated with berberine, the proliferation, migration, invasion, clonogenesis, apoptosis and cell cycle were measured, with determination of Hedgehog signaling pathway activity. Following establishment of mouse model of HCT116 xenograft tumor, the efficacies of berberine on carcinogenesis, pathological manifestation and malignant phenotypes of CRC were examined, with analysis of Hedgehog signaling axis in HCT116 xenograft tumor tissues. Additionally, toxicological study of berberine was conducted on zebrafish. RESULTS: Berberine was discovered to suppress the proliferation, migration, invasion and clonogenesis of HCT116 cells and SW480 cells. Furthermore, berberine caused cell apoptosis and blockaded cell cycle at phase G0/G1 in CRC cells, with dampened Hedgehog signaling cascade. In HCT116 xenograft tumor of nude mice, berberine inhibited tumor growth, alleviated pathological score, and promoted apoptosis and cell cycle arrest in tumor tissues, through constraining Hedgehog signaling. The toxicological study of berberine on zebrafish indicated that berberine incurred damage to the liver and heart of zebrafish at high dosage and prolonged administration. CONCLUSIONS: Taken together, berberine may inhibit the malignant phenotypes of CRC through diminishing Hedgehog signaling cascade. However, the potential adverse reactions should be taken into account upon abuse of berberine.

Ursolic Acid Suppresses Colorectal Cancer by Down-Regulation of Wnt/ß-Catenin Signaling Pathway Activity.

Overwhelming evidence points to an abnormally active Wnt/ß-catenin signaling as a key player in colorectal cancer (CRC) pathogenesis. Ursolic acid (UA) is a pentacyclic triterpenoid that has been found in a broad variety of fruits, spices, and medicinal plants. UA has been shown to have potent bioactivity against a variety of cancers, including CRC, with the action mechanism obscure. Our study tried to learn more about the efficacy of UA on CRC and its functional mechanism amid the Wnt/ß-catenin signaling cascade. We determined the efficacy of UA on CRC SW620 cells with respect to the proliferation, migration, clonality, apoptosis, cell cycle, and Wnt/ß-catenin signaling cascade, with assessment of the effect of UA on normal colonic NCM460 cells. Also, the effects of UA on the tumor development, apoptosis, cell cycle, and Wnt/ß-catenin signaling axis were evaluated after a subcutaneous SW620 xenograft tumor model was established in mice. In this work, we showed that UA drastically suppressed proliferation, migration, and clonality; induced apoptosis; and arrested the cell cycle at the G0/G1 phase of SW620 cells, without the influence on NCM460 cells, accompanied by weakened activity of the Wnt/ß-catenin signaling pathway. Besides, UA markedly deterred the growth of the xenograft tumor, ameliorated pathological features, triggered apoptosis, and arrested the cell cycle in xenograft CRC tissue, by lessening the Wnt/ß-catenin signaling cascade. Overall, UA may inhibit the malignant phenotype, induce apoptosis, and arrest the cell cycle of CRC, potentially by attenuating the Wnt/ß-catenin signaling axis, providing insights into the mechanism for the potency of UA on CRC.

Curcumin: An epigenetic regulator and its application in cancer.

Nowadays, one of the leading causes of death in humans is cancer, which is still on the rise globally and is in great need of intense study on the pathogenic mechanism and effective therapy. Epigenetics is a discipline that studies heritable changes in gene expression without alteration of DNA sequence. Epigenetic changes mainly involve DNA methylation, histone modifications and non-coding RNA (ncRNA) expression, which are interconnected to play a crucial role in the initiation and progression of various malignancies. Curcumin is a type of plant-derived polyphenolic compound with strong bioactivity against various disorders, particularly cancer. Retrieving commonly used databases such as PubMed, Google Scholar and CNKI, we summarized recent advances in the efficacy of curcumin on cancer and its epigenetic regulation in terms of DNA methylation, histone modifications and ncRNA expression. Furthermore, we also focused on improving the bioavailability of curcumin by development of novel curcumin analogs with high bioavailability, nanoparticles-loaded drug delivery system for curcumin, and combination therapy of curcumin with other agents. This review provides comprehensive insights into the molecular mechanisms, on the basis of epigenetic regulation, underlying the clinical application of curcumin in cancer.

Peppermint essential oil: its phytochemistry, biological activity, pharmacological effect and application.

Mentha (also known as peppermint), a genus of plants in the taxonomic family Lamiaceae (mint family), is widely distributed throughout temperate regions of the world. Mentha contains various constituents that are classified as peppermint essential oil (PEO) and non-essential components. PEO, consisting mainly of menthol, menthone, neomenthol and iso-menthone, is a mixture of volatile metabolites with anti-inflammatory, antibacterial, antiviral, scolicidal, immunomodulatory, antitumor, neuroprotective, antifatigue and antioxidant activities. Mounting evidence indicates that PEO may pharmacologically protect gastrointestinal, liver, kidney, skin, respiratory, brain and nervous systems, and exert hypoglycemic and hypolipidemic effects. Clinically, PEO is used for gastrointestinal and dermatological diseases, postoperative adjuvant therapy and other fields. This review aims to address the advances in the extraction and isolation of PEO, its biological activities, pharmacological effects, toxicity and applications, with an emphasis on the efficacy of PEO on burn wounds and psoriasis, providing a comprehensive foundation for research, development and application of PEO in future.

Wnt signaling in colorectal cancer: pathogenic role and therapeutic target.

BACKGROUND: The Wnt signaling pathway is a complex network of protein interactions that functions most commonly in embryonic development and cancer, but is also involved in normal physiological processes in adults. The canonical Wnt signaling pathway regulates cell pluripotency and determines the differentiation fate of cells during development. The canonical Wnt signaling pathway (also known as the Wnt/ß-catenin signaling pathway) is a recognized driver of colon cancer and one of the most representative signaling pathways. As a functional effector molecule of Wnt signaling, the modification and degradation of ß-catenin are key events in the Wnt signaling pathway and the development and progression of colon cancer. Therefore, the Wnt signaling pathway plays an important role in the pathogenesis of diseases, especially the pathogenesis of colorectal cancer (CRC). OBJECTIVE: Inhibit the Wnt signaling pathway to explore the therapeutic targets of colorectal cancer. METHODS: Based on studying the Wnt pathway, master the biochemical processes related to the Wnt pathway, and analyze the relevant targets when drugs or inhibitors act on the Wnt pathway, to clarify the medication ideas of drugs or inhibitors for the treatment of diseases, especially colorectal cancer. RESULTS: Wnt signaling pathways include: Wnt/ß-catenin or canonical Wnt signaling pathway, planar cell polarity (Wnt-PCP) pathway and Wnt-Ca2+ signaling pathway. The Wnt signaling pathway is closely related to cancer cell proliferation, stemness, apoptosis, autophagy, metabolism, inflammation and immunization, microenvironment, resistance, ion channel, heterogeneity, EMT/migration/invasion/metastasis. Drugs/phytochemicals and molecular preparations for the Wnt pathway of CRC treatment have now been developed. Wnt inhibitors are also commonly used clinically for the treatment of CRC. CONCLUSION: The development of drugs/phytochemicals and molecular inhibitors targeting the Wnt pathway can effectively treat colorectal cancer clinically.

Berberine suppresses colorectal cancer by regulation of Hedgehog signaling pathway activity and gut microbiota.

BACKGROUND: A growing body of evidence reveals that dysregulation of Hedgehog signaling pathway and dysbiosis of gut microbiota are associated with the pathogenesis of colorectal cancer (CRC). Berberine, a botanical benzylisoquinoline alkaloid, possesses powerful activities against various malignancies including CRC, with the underlying mechanisms to be illuminated. PURPOSE: The present study investigated the potencies of berberine on CRC and deciphered the action mechanisms in the context of Hedgehog signaling cascade and gut microbiota. METHODS: The effects of berberine on the malignant phenotype, apoptosis, cell cycle and Hedgehog signaling of CRC cells were examined in vitro. In azoxymethane/dextran sulfate sodium-caused mouse CRC, the efficacies of berberine on the carcinogenesis, pathological profile, apoptosis, cell cycle and Hedgehog signaling were determined in vivo. Also, the influences of berberine on gut microbiota in CRC mice were assessed by high-throughput DNA sequencing analysis of 16S ribosomal RNA of fecal microbiome in CRC mice. RESULTS: In the present study, berberine was found to dampen the proliferation, migration, invasion and colony formation of CRC cells, without toxicity to normal colonic cells. Additionally, berberine induced apoptosis and arrested cell cycle at G0/G1 phase in CRC cells, accompanied by reduced Hedgehog signaling pathway activity in vitro. In mouse CRC, berberine suppressed tumor growth, ameliorated pathological manifestations, and potentially induced the apoptosis and cell cycle arrest of CRC, with lowered Hedgehog signaling cascade in vivo. Additionally, berberine decreased ß-diversity of gut microbiota in CRC mice, without influence on α-diversity. Berberine also enriched probiotic microbes and depleted pathogenic microbes, and modulated the functionality of gut microbiota in CRC mice. CONCLUSIONS: Overall, berberine may suppress colorectal cancer, orchestrated by down-regulation of Hedgehog signaling pathway activity and modulation of gut microbiota.

Ursolic acid inhibits the activation of smoothened-independent non-canonical hedgehog pathway in colorectal cancer by suppressing AKT signaling cascade.

It is being brought to light that smoothened (SMO)-independent non-canonical Hedgehog signaling is associated with the pathogenesis of various cancers. Ursolic acid (UA), a pentacyclic triterpenoid present in many medicinal herbs, manifests potent effectiveness against multiple malignancies including colorectal cancer (CRC). In our previous study, UA was found to protect against CRC in vitro by suppression of canonical Hedgehog signaling cascade. Here, the influence of UA on SMO-independent non-canonical Hedgehog signaling in CRC was investigated in the present study, which demonstrated that UA hampered the proliferation and migration, induced the apoptosis of HCT-116hSMO- cells with SMO gene knockdown, accompanied by the augmented expression of the suppressor of fused (SUFU), and lessened levels of MYC (c-Myc), glioma-associated oncogene (GLI1) and Sonic Hedgehog (SHH), and lowered phosphorylation of protein kinase B (PKB, AKT), suggesting that UA diminished non-canonical Hedgehog signal transduction in CRC. In HCT-116hSMO- xenograft tumor, UA ameliorated the symptoms, impeded the growth and caused the apoptosis of CRC, with heightened SUFU expression, and abated levels of MYC, GLI1, and SHH, and mitigated phosphorylation of AKT, indicating that UA down-regulated non-canonical Hedgehog signaling cascade in CRC. Taken together, UA may alleviate CRC by suppressing AKT signaling-dependent activation of SMO-independent non-canonical Hedgehog pathway.

Suppression of colitis-associated colorectal cancer by scutellarin through inhibiting Hedgehog signaling pathway activity.

BACKGROUND: Colitis-associated colorectal cancer (CAC) is a specific type of colorectal cancer (CRC) and mainly develops from long-term intestinal inflammation. Mounting evidence reveals that activated Hedgehog signaling pathway plays a vital role in the pathogenesis of CRC. Scutellarin is a type of phytochemical flavonoid with a powerful efficacy on various malignancies, including CRC. AIM: Here, we studied the therapeutic effect of scutellarin on CRC and its direct regulating targets. METHODS: The CAC model in mice was established by azomethane oxide (AOM) and sodium dextran sulfate (DSS), followed by detection of the efficacies of scutellarin on the carcinogenesis, apoptosis, inflammation, Hedgehog signaling cascade and complicated inflammatory networks in CAC tissues of mice. In CRC SW480 cells, the effects of scutellarin on malignant phenotype, apoptosis and Hedgehog signaling were examined. In TNF-α-stimulated IEC-6 intestinal epithelial cells, the actions of scutellarin on inflammatory response and Hedgehog signals were assessed as well. RESULTS: Scutellarin significantly ameliorated AOM/DSS-caused CAC in mice and induced apoptosis in CAC tissues of mice, by inhibiting NF-κB (nuclear factor kappa B) -mediated inflammation and Hedgehog signaling axis. RNA-seq and transcriptome analysis indicated that scutellarin regulated complicated inflammatory networks in mouse CAC. Also, scutellarin suppressed the proliferation, migration, colony formation, and induced apoptosis of SW480 cells by down-regulation of Hedgehog signaling pathway activity. Additionally, scutellarin lessened NF-κB-mediated inflammatory response in TNF-α-stimulated IEC-6 cells, by attenuating Hedgehog signaling cascade. CONCLUSION: Scutellarin potently ameliorates CAC by suppressing Hedgehog signaling pathway activity, underpinning the promising application of scutellarin to CRC in clinical settings.

Ubiquitin-Specific Peptidase 10 Protects Against Hepatic Ischaemic/Reperfusion Injury via TAK1 Signalling.

Ubiquitin-specific peptidase 10 (USP10) protein is a deubiquitination enzyme involved in many important biological processes. However, the function of USP10 in hepatic ischaemic/reperfusion (I/R) injury remains unknown. The aim of this study was to explore the role of USP10 in hepatic I/R injury. USP10 Heterozygote mice and primary hepatocytes were used to construct hepatic I/R models. The effect of USP10 on hepatic I/R injury was examined via pathological and molecular analyses. Our results indicated that USP10 was significantly downregulated in the livers of mice after hepatic I/R injury and in hepatocytes subjected to hypoxia/reoxygenation stimulation. USP10 Heterozygote mice exhibited exacerbated hepatic I/R injury, as evidenced by enhanced liver inflammation via the NF-κB signalling pathway and increased hepatocyte apoptosis. Additionally, USP10 overexpression inhibited hepatocyte inflammation and apoptosis in hepatic I/R injury in vitro and in vivo. Mechanistically, our study demonstrated that USP10 knockdown exerted its detrimental effects on hepatic I/R injury by inducing activation of the transforming growth factor ß-activated kinase 1 (TAK1)-JNK/p38 signalling pathways. TAK1 was required for USP10 function in hepatic I/R injury as TAK1 inhibition abolished USP10 function in vitro. In conclusion, our study demonstrated that USP10 plays a protective role in hepatic I/R injury by inhibiting the activation of the TAK1-JNK/p38 signalling pathways. Modulation of USP10/TAK1 might be a promising strategy to prevent this pathological process.

Tripartite Motif 8 Deficiency Relieves Hepatic Ischaemia/reperfusion Injury via TAK1-dependent Signalling Pathways.

Tripartite motif (Trim) 8 is an E3 ubiquitin ligase, interacting with and ubiquitinating diverse substrates, and is closely involved in innate immunity. However, the function of Trim8 in hepatic ischaemia/reperfusion (I/R) injury remains largely unknown. The aim of this study is to explore the role of Trim8 in hepatic I/R injury. Trim8 gene knockout mice and primary hepatocytes were used to construct hepatic I/R models. The effect of Trim8 on hepatic I/R injury was analysed via pathological and molecular analyses. The results indicated that Trim8 was significantly upregulated in liver of mice subjected to hepatic I/R injury. Trim8 knockout relieved hepatocyte injury triggered by I/R. Silencing of Trim8 expression alleviated hepatic inflammation responses and inhibited apoptosis in vitro and in vivo. Mechanistically, our study suggests that Trim8 deficiency may elicit hepatic protective effects by inhibiting the activation of transforming growth factor ß-activated kinase 1 (TAK1)-p38/JNK signalling pathways. TAK1 was required for Trim8 function in hepatic I/R injury as TAK1 activation abolished Trim8 function in vitro. In conclusion, our study demonstrates that Trim8 deficiency plays a protective role in hepatic I/R injury by inhibiting the activation of TAK1-dependent signalling pathways.

Expression analysis of long non-coding RNAs in a renal ischemia-reperfusion injury model.

PURPOSE: To investigate the long non-coding RNAs (lncRNAs) profile on renal ischemia reperfusion in a mouse model. METHODS: Microarray analysis was used to study the expression of misregulated lncRNA in a mouse model of renal ischemia reperfusion(I/R) with long ischemia time. Quantitative real-time PCR (qPCR) was used to verify the expression of selected lncRNAs and mRNAs.The potential functions of the lncRNA was analyzed by bioinformatics tools and databases. RESULTS: Kidney function was impaired in I/R group compared to the normal group. Analysis showed that a total of 2267 lncRNAs and 2341 messenger RNAs (mRNAs) were significantly expressed in I/R group (≥2.0-fold, p < 0.05).The qPCR result showed that lncRNAs and mRNAs expression were consistent with the microarray analysis. The co-expression network profile analysis based on five validated lncRNAs and 203 interacted mRNAs showed it existed a total of 208 nodes and 333 connections. The GO and KEEG pathway analysis results showed that multiple lncRNAs are involved the mechanism of I/R. CONCLUSION: Multiple lncRNAs are involved in the mechanism of I/R.These analysis results will help us to further understand the mechanism of I/R and promote the new methods targeted at lncRNA to improve I/R injury.

Anti-silencing function 1B histone chaperone promotes cell proliferation and migration via activation of the AKT pathway in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is one of the most common malignancies. Anti-silencing function 1B histone chaperone (ASF1B) has been reported to be involved in various diseases. However, its role in ccRCC is largely unknown. In the present study, using genetic data and clinical information obtained from the TCGA data portal and GEO database, we found that ASF1B was highly expressed in ccRCC cancer tissue compared with normal tissue, and ASF1B expression was positively correlated with tumor stage, tumor grade and patient survival. The function of ASF1B in cell proliferation and migration was assessed by pathological and molecular analyses. The results showed that ASF1B overexpression significantly enhanced the proliferation and migration of 786-O cells and Caki-1 cells, while silencing ASF1B expression significantly inhibited the proliferation and migration. In addition, ASF1B overexpression enhanced cell proliferation by upregulating PCNA and downregulating P27 expression and promoted cell migration by upregulating MMP2 and MMP9. Furthermore, the phosphorylation levels of protein kinase B (AKT) and P-P70 S6K1 were significantly upregulated in the ASF1B overexpression group. More importantly, AKT inhibitor blocked the promotional effect of ASF1B on proliferation and migration. In summary, the present study demonstrated that ASF1B overexpression promoted tumor cell proliferation and migration, which was dependent on the AKT/P70 S6K1 pathway.

Expression analysis of long non-coding RNAs in a renal ischemia-reperfusion injury model

Abstract Purpose: To investigate the long non-coding RNAs (lncRNAs) profile on renal ischemia reperfusion in a mouse model. Methods: Microarray analysis was used to study the expression of misregulated lncRNA in a mouse model of renal ischemia reperfusion(I/R) with long ischemia time. Quantitative real-time PCR (qPCR) was used to verify the expression of selected lncRNAs and mRNAs.The potential functions of the lncRNA was analyzed by bioinformatics tools and databases. Results: Kidney function was impaired in I/R group compared to the normal group. Analysis showed that a total of 2267 lncRNAs and 2341 messenger RNAs (mRNAs) were significantly expressed in I/R group (≥2.0-fold, p < 0.05).The qPCR result showed that lncRNAs and mRNAs expression were consistent with the microarray analysis. The co-expression network profile analysis based on five validated lncRNAs and 203 interacted mRNAs showed it existed a total of 208 nodes and 333 connections. The GO and KEEG pathway analysis results showed that multiple lncRNAs are involved the mechanism of I/R. Conclusion: Multiple lncRNAs are involved in the mechanism of I/R.These analysis results will help us to further understand the mechanism of I/R and promote the new methods targeted at lncRNA to improve I/R injury.

A preliminary identification of Rf*-A619, a novel restorer gene for CMS-C in maize (Zea mays L.).

C-type cytoplasmic male sterility (CMS-C) is widely utilized for hybrid maize seed production. However, genetic mechanisms underlying the fertility restoration are very complicated. At present, there is a divergence on the number of fertility restorer genes in maize inbred line A619 for CMS-C. To further elucidate the restoring mechanism of A619, we used genetic analysis and molecular markers to confirm the restorer genes of maize inbred line A619 for C-type male sterile line C48-2 in this study. Firstly, the fertility segregations of (C48-2 × A619)F2 populations were investigated under three environments during 2013-2015. The segregation ratio of fertile and sterile plants in the F2 population fit to 15:1 via chi-square test and this result suggested that there are two dominant restorer genes in A619 for CMS-C, i.e., Rf4 and a novel gene named Rf*-A619. Next, based on the sequence differences between Rf4 and its recessive allelic rf4, a novel dominant marker F2/R2 was developed and validated to genotyping Rf4 in the F2 population. Through genotypic analysis, we found that there were a certain amount of fertile individuals without Rf4 which accounted for 3/16 in the F2 population via chi-square test at the 0.05 level. These results provided another proof to sustain that the inbred line A619 contains one additional restorer gene for CMS-C fertility restoration except Rf4. At last, we used one SSR marker which is tightly linked with the dominant restorer gene Rf5 to analyze those fertile plants without Rf4 in the F2 population. The PCR amplification results showed that Rf*-A619 is not allelic to Rf5 but a novel restorer gene for CMS-C. These results not only provide a basis for the mapping and characterization of a novel restorer gene but also give a new insight into the mechanism of CMS-C fertility restoration.

[Setting up a risk prediction model on metabolic syndrome among 35-74 year-olds based on the Taiwan MJ Health-checkup Database].

OBJECTIVE: This study aimed to provide an epidemiological modeling method to evaluate the risk of metabolic syndrome (MS) development in the coming 5 years among 35-74 year-olds from Taiwan. METHODS: A cohort of 13 973 subjects aged 35-74 years who did not have metabolic syndrome but took the initial testing during 1997-2006 was formed to derive a risk score which tended to predict the incidence of MS. Multivariate logistic regression was used to derive the risk functions and using the 'check-up center' (Taipei training cohort)as the overall cohort. Rules based on these risk functions were evaluated in the remaining three centers (as testing cohort). Risk functions were produced to detect the MS on a training sample using the multivariate logistic regression models. Started with those variables that could predict the MS through univariate models, we then constructed multivariable logistic regression models in a stepwise manner which eventually could include all the variables. The predictability of the model was evaluated by areas under curve (AUC) the receiver-operating characteristic (ROC) followed by the testification of its diagnostic property on the testing sample. Once the final model was defined, the next step was to establish rules to characterize 4 different degrees of risks based on the cut points of these probabilities, after being transformed into normal distribution by log-transformation. RESULTS: At baseline, the range of the proportion of MS was 23.9% and the incidence of MS in 5-years was 11.7% in the non-MS cohort. The final multivariable logistic regression model would include ten risk factors as: age, history of diabetes, contractive pressure, fasting blood-glucose, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol, body mass index and blood uric acid. AUC was 0.827(95% CI: 0.814-0.839) that could predict the development of MS within the next 5 years. The curve also showed adequate performance in the three tested samples, with the AUC and 95% CI as 0.813 (0.789-0.837), 0.826 (0.800-0.852) and 0.794 (0.768-0.820), respectively. After labeling the degrees of the four risks, it was showed that over 17.6% of the incidence probability was in the population under mediate risk while over 59.0% of them was in the high risk group, respectively. CONCLUSION: Both predictability and reliability of our Metabolic Syndrome Risk Score Model, derived based on Taiwan MJ Longitudinal Health-checkup-based Population Database, were relatively satisfactory in the testing cohort. This model was simple, with practicable predictive variables and feasible form on degrees of risk. This model not only could help individuals to assess the situation of their own risk on MS but could also provide guidance on the group surveillance programs in the community regarding the development of MS.

Eye care use among rural adults in China: the Handan Eye Study.

PURPOSE: To assess the use of eye care services in a rural population in North China and to analyze the factors associated with underuse of these services. METHODS: In a cross-sectional population-based study, demographic, health and vision-related information including use of eye care services were determined during a face-to-face interview. A single visit to an eye care provider qualified as "use" of eye care services. RESULTS: Of 6612 participants, 754 (11.4%, 95% confidence interval, CI, 8.7-14.1%) had used eye care services. The most common reason cited for not seeing an eye care provider was "no need" (n = 5754). Of the 5754 who thought that there was no need to see an ophthalmologist, 3458 (60.1%) were found to have one or more type of eye disease, including glaucoma (56, 1.0%), cataract (1056, 18.4%), age-related macular degeneration (AMD; 164, 2.9%) and refractive error (3048, 53.0%). Also, 74 (1.3%) and 409 (7.1%) of the 5754 participants had visual impairment (<20/60) according to best-corrected visual acuity and presenting visual acuity, respectively. In a multiple regression model, participants who had glaucoma (adjusted odds ratio, OR, 4.0, 95% CI 3.0-5.4), AMD (adjusted OR 1.6, 95% CI 1.2-2.3) or refractive error (adjusted OR 1.4, 95% CI 1.1-1.8), were more likely to visit an eye care provider. CONCLUSION: A high proportion of the Chinese rural population had never used eye care services although three fifths had eye diseases. Further efforts towards better education of the general population about common eye problems as well as increasing the number of ocular health providers would be necessary in future.

[Association analysis of serum γ-glutamyltransferase with risk of metabolic syndrome in Beijing healthy population].

OBJECTIVE: To study the association of γ-glutamyltransferase (GGT) with the development of the metabolic syndrome (MS). METHODS: Subjects without MS at baseline in Beijing health-checkup database during 2003 and 2010, from MJ Health Management Centers, with complete key variables and at least two records were selected to derive a cohort, after comparison of the median trend, and analysis with Cox regression models and spline regression models, and to study the association of GGT with the development of MS and the dose-response relationship trend. RESULTS: Out of 10 076 (46.20/1 000 person-years) in the cohort, 1 181 subjects developed MS after follow-up of 2.54 years on average. With adjustment for age, gender, cigarette smoking, alcohol intake, physical activity, body mass index, family history of cardiovascular disease, systolic blood pressure, white blood cell count, high-density lipoprotein cholesterol, fasting blood glucose, triglycerides and C-reacted protein in Cox regression model, the hazard ratio for MS in quartiles 4 level of GGT was 1.60(95% confidence interval: 1.18-2.17). After adjustment with the use of spline regression model, the dose-response relationship showed an increasing curve with a degressive slope. The elevated GGT level was associated with an increased risk of MS, but the contribution of GGT augmented less when the GGT level was high. CONCLUSION: The elevated GGT level, an important risk factor and predictor, may be associated with an increased risk of MS.