Interaction of tetracycline and copper co-intake in inducing antibiotic resistance genes and potential pathogens in mouse gut.

The widespread use of copper and tetracycline as growth promoters in the breeding industry poses a potential threat to environmental health. Nevertheless, to the best of our knowledge, the potential adverse effects of copper and tetracycline on the gut microbiota remain unknown. Herein, mice were fed different concentrations of copper and/or tetracycline for 6 weeks to simulate real life-like exposure in the breeding industry. Following the exposure, antibiotic resistance genes (ARGs), potential pathogens, and other pathogenic factors were analyzed in mouse feces. The co-exposure of copper with tetracycline significantly increased the abundance of ARGs and enriched more potential pathogens in the gut of the co-treated mice. Copper and/or tetracycline exposure increased the abundance of bacteria carrying either ARGs, metal resistance genes, or virulence factors, contributing to the widespread dissemination of potentially harmful genes posing a severe risk to public health. Our study provides insights into the effects of copper and tetracycline exposure on the gut resistome and potential pathogens, and our findings can help reduce the risks associated with antibiotic resistance under the One Health framework.

Global biogeographic distribution of Bathyarchaeota in paddy soils.

Bathyarchaeota, known as key participants of global elements cycling, is highly abundant and diverse in the sedimentary environments. Bathyarchaeota has been the research spotlight on sedimentary microbiology; however, its distribution in arable soils is far from understanding. Paddy soil is a habitat similar to freshwater sediments, while the distribution and composition of Bathyarchaeota in paddy soils have largely been overlooked. In this study, we collected 342 in situ paddy soil sequencing data worldwide to illuminate the distribution patterns of Bathyarchaeota and explore their potential ecological functions in paddy soils. The results showed that Bathyarchaeota is the dominant archaeal lineage, and Bathy-6 is the most predominant subgroup in paddy soils. Based on random forest analysis and construction of a multivariate regression tree, the mean annual precipitation and mean annual temperature are identified as the factors significantly influencing the abundance and composition of Bathyarchaeota in paddy soils. Bathy-6 was abundant in temperate environments, while other subgroups were more abundant in sites with higher rainfall. There are highly frequent associations between Bathyarchaeota and methanogens and ammonia-oxidizing archaea. The interactions between Bathyarchaeota and microorganisms involved in carbon and nitrogen metabolism imply a potential syntrophy between these microorganisms, suggesting that members of Bathyarchaeota could be important participants of geochemical cycle in paddy soils. These results shed light on the ecological lifestyle of Bathyarchaeota in paddy soils, and provide some baseline for further understanding Bathyarchaeota in arable soils. IMPORTANCE Bathyarchaeota, the dominant archaeal lineage in sedimentary environments, has been the spotlight of microbial research due to its vital role in carbon cycling. Although Bathyarchaeota has been also detected in paddy soils worldwide, its distribution in this environment has not yet been investigated. In this study, we conducted a global scale meta-analysis and found that Bathyarchaeota is also the dominant archaeal lineage in paddy soils with significant regional abundance differences. Bathy-6 is the most predominant subgroup in paddy soils, which differs from sediments. Furthermore, Bathyarchaeota are highly associated with methanogens and ammonia-oxidizing archaea, suggesting that they may be involved in the carbon and nitrogen cycle in paddy soil. These interactions provide insight into the ecological functions of Bathyarchaeota in paddy soils, which will be the foundation of future studies regarding the geochemical cycle in arable soils and global climate change.

Improving Catalytic Activity, Acid-Tolerance, and Thermal Stability of Glutathione Peroxidase by Systematic Site-Directed Selenocysteine Incorporation.

Glutathione peroxidase (GPx) is an important antioxidant enzyme. Selenocysteine (Sec)-containing GPxs (Sec-GPxs) are usually superior to their conventional cysteine-containing counterparts (Cys-GPxs), which make up the majority of the natural GPxs but display unsuitable activity and stability for industrial applications. This study first heterologously expressed and characterized a Cys-GPx from Lactococcus lactis (LlGPx), systematically exchanged all the three Cys to Sec and introduced an extra Sec. The results showed that the insertion of Sec at the active site could effectively increase the enzyme activity and confer a lower optimal pH value on the mutants. The double mutant C36U/L157U increased by 2.65 times (5.12 U/mg). The thermal stability of the C81U mutant was significantly improved. These results suggest that site-directed Sec incorporation can effectively improve the enzymatic properties of LlGPx, which may be also used for the protein engineering of other industrial enzymes containing catalytic or other functional cysteine residues.

A reliable method of high performance liquid chromatography coupled with inductively coupled plasma mass spectrometry for determining selenoamino acids in selenoproteins from Lactococcus lactis.

A reliable method for simultaneous determination of four organic selenium species by HPLC-ICP-MS was developed and implemented in determining organic selenoamino acids (Se-AAs) in selenoproteins from Lactococcus lactis (L. lactis) NZ9000. The method consisted of liberating Se-AAs from selenoproteins using ultrasound-assisted protease hydrolysis, and quantitatively detecting Se-AA speciations by HPLC-ICP-MS. After optimizations of proteolysis conditions, chromatographic conditions and determination conditions, the established method could efficiently separate the four Se-AAs, including SeCys, SeCys2, SeMeCys and SeMet within 10 min. It presented high sensitivity with the limits of detection and quantitation in the range of 0.197∼0.240 µg∙L-1 and 0.788∼0.960 µg∙L-1, respectively, good repeatability with a relative standard deviation (RSD) of less than 5%, and good recovery in the desired floating range of 90%∼105%, verifying the good accuracy. The method successfully detected four selenium species in the purified glutathione peroxidase (LlGPx) overexpressed in L. lactis NZ9000, SeCys (0.9716∼1.6784 µg∙g-1), SeCys2 (1.0695∼1.2124 µg∙g-1), SeMeCys (0.7288∼0.7984 µg∙g-1) and SeMet (1.0058∼1.9571 µg∙g-1), accounting for up to 80.14% of total selenium. There was no difference of order of magnitude in the four Se-AAs, indirectly indicating the random incorporation of selenium into selenoprotein LlGPx in L. lactis NZ9000. This work throws new light on the identification and biosynthesis of organic selenium species in selenoproteins and selenium-riched organisms like L. lactis.

Mechanisms Affecting the Biosynthesis and Incorporation Rate of Selenocysteine.

Selenocysteine (Sec) is the 21st non-standard proteinogenic amino acid. Due to the particularity of the codon encoding Sec, the selenoprotein synthesis needs to be completed by unique mechanisms in specific biological systems. In this paper, the underlying mechanisms for the biosynthesis and incorporation of Sec into selenoprotein were comprehensively reviewed on five aspects: (i) the specific biosynthesis mechanism of Sec and the role of its internal influencing factors (SelA, SelB, SelC, SelD, SPS2 and PSTK); (ii) the elements (SECIS, PSL, SPUR and RF) on mRNA and their functional mechanisms; (iii) the specificity (either translation termination or translation into Sec) of UGA; (iv) the structure-activity relationship and action mechanism of SelA, SelB, SelC and SelD; and (v) the operating mechanism of two key enzyme systems for inorganic selenium source flow before Sec synthesis. Lastly, the size of the translation initiation interval, other action modes of SECIS and effects of REPS (Repetitive Extragenic Palindromic Sequences) that affect the incorporation efficiency of Sec was also discussed to provide scientific basis for the large-scale industrial fermentation for the production of selenoprotein.

miR­125/CDK2 axis in cochlear progenitor cell proliferation.

Hearing loss ranks fourth among the principal causes of disability worldwide, and manipulation of progenitor cells may be a key strategy for hair cell regeneration. The present study investigated the role and mechanism of miR­125 on the proliferation of cochlear progenitor cells (CPCs). CPCs were isolated from the cochleae of neonatal rats, and their morphology was observed. Furthermore, the differentiation ability of CPCs was determined by assessing the expression of 5­bromodeoxyuridine (BrdU), nestin and myosin VII by immunofluorescence. The expression levels of miR­125 and cyclin­dependent kinase 2 (CDK2) as well as the cell proliferation of CPCs were assessed. In addition, following gain­ and loss­of­function assays, the cell cycle was examined by flow cytometry, and the expression levels of miR­125, CDK2, proliferating cell nuclear antigen (PCNA) and nestin were determined by reverse transcription­quantitative PCR and western blotting. The binding sites between miR­125 and CDK2 were predicted by TargetScan and identified by the dual luciferase reporter assay. The results demonstrated that different types of progenitor spheres were observed from CPCs with positive expression of BrdU, nestin and myosin VII. Following in vitro incubation for 2, 4 and 7 days, the spheres were enlarged, and CPC proliferation gradually increased and reached a plateau after further incubation for 3 days. Furthermore, the expression levels of nestin and PCNA in CPCs increased and then decreased during in vitro incubation for 2, 4 and 7 days. Following this incubation, the expression levels of miR­125 in CPCs decreased; thereafter, its expression increased, and the expression pattern was different from that of CDK2. In addition, miR­125 overexpression in CPCs decreased the expression of CDK2 and the number of cells in the S phase. Different expression patterns were found in CPCs in response to the miR­125 knockdown. In addition, miR­125 directly targeted CDK2. Simultaneous knockdown of miR­125 and CDK2 enhanced CPC proliferation compared with CDK2 knockdown alone. Taken together, the findings from the present study suggested that miR­125 may inhibit CPC proliferation by downregulating CDK2. The present study may provide a novel therapeutic direction for treatment of hearing loss.

MicroRNA-375 represses tumor angiogenesis and reverses resistance to sorafenib in hepatocarcinoma.

Sorafenib was originally identified as an inhibitor of multiple oncogenic kinases and remains the first-line systemic therapy for advanced hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) have been reported to play critical roles in the initiation, progression, and drug resistance of HCC. In this study, we aimed to identify sorafenib-induced miRNAs and demonstrate their regulatory roles. First, we identified that the expression of the tumor-suppressive miRNA miR-375 was significantly induced in hepatoma cells treated with sorafenib, and miR-375 could exert its antiangiogenic effect partially via platelet-derived growth factor C (PDGFC) inhibition. Then, we demonstrated that sorafenib inhibited PDGFC expression by inducing the expression of miR-375 and a transcription factor, achaete-scute homolog-1 (ASH1), mediated the induction of miR-375 by sorafeinb administration in hepatoma cells. Finally, we verified that the expression of miR-375 was reduced in sorafenib-resistant cells and that the restoration of miR-375 could resensitize sorafenib-resistant cells to sorafenib partially by the degradation of astrocyte elevated gene-1 (AEG-1). In conclusion, our data demonstrate that miR-375 is a critical determinant of HCC angiogenesis and sorafenib tolerance, revealing a novel miRNA-mediated mechanism underlying sorafenib treatment.

Clinical application of combined detection of SARS-CoV-2-specific antibody and nucleic acid.

BACKGROUND: The global outbreak of human severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection represents an urgent need for readily available, accurate and rapid diagnostic tests. Nucleic acid testing of respiratory tract specimens for SARS-CoV-2 is the current gold standard for diagnosis of coronavirus disease 2019 (COVID-19). However, the diagnostic accuracy of reverse transcription polymerase chain reaction (RT-PCR) tests for detecting SARS-CoV-2 nucleic acid may be lower than optimal. The detection of SARS-CoV-2-specific antibodies should be used as a serological non-invasive tool for the diagnosis and management of SARS-CoV-2 infection. AIM: To investigate the diagnostic value of SARS-CoV-2 IgM/IgG and nucleic acid detection in COVID-19. METHODS: We retrospectively analyzed 652 suspected COVID-19 patients, and 206 non-COVID-19 patients in Wuhan Integrated TCM and Western Medicine Hospital. Data on SARS-CoV-2 nucleic acid tests and serum antibody tests were collected to investigate the diagnostic value of nucleic acid RT-PCR test kits and immunoglobulin (Ig)M/IgG antibody test kits. The χ2 test was used to compare differences between categorical variables. A 95% confidence interval (CI) was provided by the Wilson score method. All analyses were performed with IBM SPSS Statistics version 22.0 (IBM Corp., Armonk, NY, United States). RESULTS: Of the 652 suspected COVID-19 patients, 237 (36.3%) had positive nucleic acid tests, 311 (47.7%) were positive for IgM, and 592 (90.8%) were positive for IgG. There was a significant difference in the positive detection rate between the IgM and IgG test groups (P < 0.001). Using the RT-PCR results as a reference, the specificity, sensitivity, and accuracy of IgM/IgG combined tests for SARS-CoV-2 infection were 98.5%, 95.8%, and 97.1%, respectively. Of the 415 suspected COVID-19 patients with negative nucleic acid test results, 366 had positive IgM/IgG tests with a positive detection rate of 88.2%. CONCLUSION: Our data indicate that serological IgM/IgG antibody combined test had high sensitivity and specificity for the diagnosis of SARS-CoV-2 infection, and can be used in combination with RT-PCR for the diagnosis of SARS-CoV-2 infection.

SmbHLH53 is relevant to jasmonate signaling and plays dual roles in regulating the genes for enzymes in the pathway for salvianolic acid B biosynthesis in Salvia miltiorrhiza.

Basic helix-loop-helix (bHLH) transcription factors play essential roles in myriad regulatory processes, including secondary metabolism. In this study with Salvia miltiorrhiza, we isolated and characterized SmbHLH53, which encodes a bHLH family member. Expression of this gene was significantly induced by wounding and multiple hormones, including methyl jasmonic acid; transcript levels were highest in the leaves and roots. Phylogenetic analysis indicated that SmbHLH53 clusters withAtbHLH17 and AtbHLH13, two negative regulators of jasmonate (JA) responses, and is localized in the nucleus and cell membrane. Yeast two-hybrid and bimolecular fluorescent complementation assays indicated that SmbHLH53 forms a homodimer as well as a heterodimer with SmbHLH37. It also interacts with both SmJAZs1/3/8 and SmMYC2, the core members of the JA signal pathway. Unexpectedly, we noted that overexpression of SmbHLH53 did not significantly influence the concentrations of rosmarinic acid and salvianolic acid B in transgenic plants. Results from yeast one-hybrid assays showed that SmbHLH53 binds to the promoters of SmTAT1, SmPAL1, and Sm4CL9, the key genes for enzymes in the pathway for phenolic acid synthesis. Assays of transient transcriptional activity demonstrated that SmbHLH53 represses the promoter of SmTAT1 while activating the promoter of Sm4CL9. Thus, the present work revealed that SmbHLH53 may play dual roles in regulating the genes for enzymes in the pathway for Sal B biosynthesis.

Programmed Death Ligand-1 (PD-L1) Regulated by NRF-2/MicroRNA-1 Regulatory Axis Enhances Drug Resistance and Promotes Tumorigenic Properties in Sorafenib-Resistant Hepatoma Cells.

Sorafenib, a multityrosine kinase inhibitor, is a standard treatment for advanced hepatocellular carcinoma (HCC), but the clinical response to sorafenib is seriously limited by drug resistance. Programmed death ligand-1 (PD-L1) is one of the most important inhibitory molecules involved in tumor immune evasion. Recently, it has been reported that PD-L1 could play crucial roles in drug resistance of many kinds of cancers. However, the expression, function, and regulation of PD-L1 in sorafenib-resistant hepatoma cells remain unclear. In this study, we reported that PD-L1 was overexpressed in sorafenib-resistant hepatoma cells, and shRNA-mediated PD-L1 depletion attenuated drug resistance and suppressed the migration, invasion, colony formation, and tumorigenesis in sorafenib-resistant hepatoma cells in vitro and in vivo. Mechanistic investigations indicated that loss of microRNA-1 (miR-1), a tumor-suppressive microRNA, contributed to the PD-L1 upregulation in sorafenib-resistant hepatoma cells, and PD-L1 was a direct regulatory target of miR-1. Further study revealed that an oncogenic transcriptional factor, nuclear factor E2-related factor 2 (NRF-2), was induced in sorafenib-resistant hepatoma cells and inhibited expression of miR-1 in vitro. From molecular mechanism insight back to the functional verification, we eventually demonstrated that miR-1 executed its tumor-suppressive effects on drug resistance and other malignant properties in sorafenib-resistant hepatoma cells partially by PD-L1 inhibition in vitro and in vivo. In conclusion, our data suggested that a NRF-2/miR-1/PD-L1 regulatory axis contributed to the development and maintenance of drug resistance and other tumorigenic properties in sorafenib-resistant hepatoma cells and provided a potential therapeutic target for overcoming sorafenib resistance in HCC.

[Soil moisture dynamics and productivity of poplar plantations under drip and furrow irrigation managements]. / æ»´çŒä¸Žæ²ŸçŒæ ½åŸ¹æ¨æ ‘äººå·¥æž—åœŸå£¤æ°´åˆ†åŠ¨æ€ä¸Žç”Ÿäº§åŠ›.

A 9-year-old poplar plantation was cultivated by drip irrigation and furrow irrigation in the sandland of ancient Yongding River in Daxing District of Beijing. Soil moisture sensors were set up in main soil layers (20, 40, 60 and 80 cm) with most roots distributed. The intelligent collector was used to monitor soil moisture in real time to investigate soil moisture dynamics and forest productivity under different irrigation patterns. The results showed that after a single effective drip irrigation and furrow irrigation, the vertical depth of wet body formed along the tree row was 72 cm and 143 cm, and the cross-sectional area of wet body was 0.41 and 2.71 m2, respectively. The amount of irrigation was 79.20 and 776.47 m3·hm-2 respectively, with the latter being 9.8 times of the former. The duration was almost the same (11 d) when soil moisture went down to the level of slight water deficit (the soil moisture content=70% of field moisture carrying capacity) in the 0-40 cm layer where poplar absorption roots mainly distributed. From April to October 2019, total irrigation amount of three times furrow irrigation in May, July and September was 2329.41 m3·hm-2, and that of drip irrigation was 1425.60 m3·hm-2, 18 times in total. There were 109 days during which poplar trees suffered moderate water deficit (the soil moisture content ≤60% of field moisture carrying capacity) under furrow irrigation, whereas no moderate water deficit happened under drip irrigation during the whole growing season. Annual increment of standing volume was 38.92 m3·hm-2 under drip irrigation, which was 1.5 times of that under furrow irrigation (25.43 m3·hm-2). Our results suggested that different irrigation resulted in significant difference in productivity of poplar plantation.

Eukaryotic initiation factor 5A2 and human digestive system neoplasms.

Eukaryotic initiation factor 5A2 (eIF5A2), as one of the two isoforms in the family, is reported to be a novel oncogenic protein that is involved in multiple aspects of many types of human cancer. Overexpression or gene amplification of EIF5A2 has been demonstrated in many cancers. Accumulated evidence shows that eIF5A2 initiates tumor formation, enhances cancer cell growth, increases cancer cell metastasis, and promotes treatment resistance through multiple means, including inducing epithelial-mesenchymal transition, cytoskeletal rearrangement, angiogenesis, and metabolic reprogramming. Expression of eIF5A2 in cancer correlates with poor survival, advanced disease stage, as well as metastasis, suggesting that eIF5A2 function is crucial for tumor development and maintenance but not for normal tissue homeostasis. All these studies suggest that eIF5A2 is a useful biomarker in the prediction of cancer prognosis and serves as an anticancer molecular target. This review focuses on the expression, subcellular localization, post-translational modifications, and regulatory networks of eIF5A2, as well as its biochemical functions and evolving clinical applications in cancer, especially in human digestive system neoplasms.

Research on the cause of death for severe stroke patients.

AIMS AND OBJECTIVES: To explore the characteristics of mortality among severe stroke patients, analyse their causes of death and provide evidence for improving the survival rate of stroke patients. BACKGROUND: Stroke is an important fatal and disabling disease that poses a large burden on its patients, and its high death rates have caused substantial concern to the World Health Organization. DESIGN: A retrospective case-control study. METHODS: A total of 188 patients who died of stroke in the neurological intensive care unit of the First Affiliated Hospital of Chongqing Medical University from January 2012-December 2015 were selected as cases. Additionally, 188 stroke survivors from the same neurological intensive care unit were randomly selected as paired cases. The clinical characteristics of the severe stroke patient deaths were analysed, and a univariate analysis was conducted to determine potential mortality risk factors. A logistic regression analysis was then conducted to determine the independent risk factors of mortality. RESULTS: We investigated a total of 231 cases of death in neurological intensive care unit patients, 188 of whom died of stroke. Therefore, the death rate from stroke accounted for 81.3% of the total population, with ischaemic, haemorrhagic and mixed strokes accounting for 47.19%, 26.84% and 7.36% of the patients, respectively. The leading cause of death was central nervous system-related causes (central respiratory and circulatory failure, brain herniation), followed by multisystemic causes. The independent risk factors of death among the neurological intensive care unit patients were as follows: brain herniation (OR = 18.15), multiple organ failure (OR = 13.12), dyslipidemia (OR = 4.64), community-acquired lung infection (OR = 4.15), use of mechanical ventilation (OR = 3.37), hypoproteinemia (OR = 2.29), history of hypertension (OR = 2.03) and hospital-acquired pneumonia (OR = 1.75). CONCLUSIONS: The most common cause of death in stroke patients was damage to the central nervous system. Independent risk factors were brain herniation, multiple organ failure, dyslipidemia, community-acquired lung infection, the use of mechanical ventilation, hypoproteinemia, a history of hypertension and hospital-acquired pneumonia. Clinicians should be aware of the presence and possible effects of these conditions. Early prevention, monitoring and intervention to modify controllable risk factors will improve patient prognosis. RELEVANCE TO CLINICAL PRACTICE: Clinicians should be aware of the multiple independent risk factors of death and implement timely treatment measures to reduce the incidence of death in severe stroke patients.

ALDH1 Expression and the Prognosis of Lung Cancer: A Systematic Review and Meta-Analysis.

PURPOSE: Aldehyde dehydrogenase 1 (ALDH1) has been identified as a putative cancer stem cell (CSC) marker in lung cancer. However, the clinicopathological and prognostic value of this protein in lung cancer patients remains controversial. Thus, we performed a systematic review and meta-analysis of studies assessing the clinical and prognostic significance of ALDH1 expression in lung cancer. METHODS: An identification and review of publications assessing clinical or prognostic significance of ALDH1 expression in lung cancer until September 1, 2014 was undertaken. A meta-analysis was performed to clarify the association between ALDH1 expression and clinical outcomes. RESULTS: A total of 14 publications met the criteria and comprised 1926 cases. Analysis of these data showed that ALDH1 expression was not significantly associated with the patient age (OR = 0.82, 95% confidence interval [CI]: 0.45-1.50, P=0.52), tumour size (OR=0.68, 95% CI: 0.22-2.06, P=0.49), smoking status (OR=1.37, 95% CI: 0.85-2.22, P=0.19), or tumour grade (OR=1.65, 95% CI: 0.83-3.26, P=0.15). However, in the identified studies, ALDH1 expression was highly correlated with lymph node metastasis (OR=1.97, 95% CI: 1.16-3.34, P=0.01), tumour TNM staging (OR=1.68, 95% CI 1.28-2.22, P=0.0002), decreased overall survival (relative risk [RR]: 1.97,95% CI: 1.16-3.34, P =0.01) and decreased disease free survival (RR: 1.63, 95% CI: 1.01-2.64, P=0.05). CONCLUSIONS: This meta-analysis shows ALDH1 expression in lung cancer is connected with decreased overall and disease free survival and thus marks a worse prognosis.

[Determination the Change of Main Trace Elements in the Ovary with Self- and Cross-Pollination of Chinese Chestnut by ICP-MS].

Castanea mollissima Blume has potential as an non-wood forest trees that have been cultivated for thousands of years in China. In order to elucidate the trace elements of chestnut ovary, the major trace elements of self- and cross-pollination chestnut ovary were determined by inductively coupled plasma mass spectrometry. The results showed that self- and cross-pollination 5-50 d, six trace elements trends showed fluctuations. After cross-pollination 20 d, the content of Ca was up to 6.50 mg x g(-1), while the self-pollination 10 d, the content of Ca reached up to 7.77 mg x g(-1). After cross- and self-pollination pollination 30 d, the content of Mg were highest, 4.19 and 4.69 mg x g(-1), respectively. After cross-pollination 5 d, the content of Zn reached the highest, 0.038 7 mg x g(-1), while self-pollination 10d the content of Zn was 0.039 9 mg x g(-1). After self- and cross-pollination 35 d, the content of Fe were 0.022, 0.019 mg x g(-1), respectively. After cross- and self-pollination 20 d, the content of Cu were 0.056, 0.045 mg x g(-1), respectively. After self-pollination 40d, the content of Mn reaching the highest was 1.204 mg x g(-1), while cross-pollination 30 d, the content of Mn reached its maximum 0.845 mg x g(-1). The results can provide a reference for spraying fertilizer on the ovary development, thereby improving chestnut production.

MicroRNA-1 promotes apoptosis of hepatocarcinoma cells by targeting apoptosis inhibitor-5 (API-5).

Although microRNA-1 (miR-1) is a known liver cancer suppressor, the role of miR-1 in apoptosis of hepatoma cells has remained largely unknown. Our study shows that ectopic miR-1 overexpression induced apoptosis of liver hepatocellular carcinoma (HepG2) cells. Apoptosis inhibitor 5 (API-5) was found to be a potential regulator of miR-1 induced apoptosis, using a bioinformatics approach. Furthermore, an inverse relationship between miR-1 and API-5 expression was observed in human liver cancer tissues and adjacent normal liver tissues. Negative regulation of API-5 expression by miR-1 was demonstrated to promote apoptosis of HepG2 cells. Our study provides a novel regulatory mechanism of miR-1 in the apoptosis of hepatoma cells.

Reduced Krüppel-like factor 17 (KLF17) expression correlates with poor survival in patients with gastric cancer.

BACKGROUND AND AIMS: To investigate the expression and prognostic significance of Krüppel-like factor 17 (KLF17) in human gastric cancer. METHODS: KLF17 expressions in 158 paraffin-embedded gastric cancer samples were analyzed using immunohistochemistry. In addition, KLF17 expressions patterns in three fresh gastric cancer tissues and noncancerous gastric mucosa were examined by Western blotting. The correlation between KLF17 expression and clinicopathological factors as well as patient survival was investigated. RESULTS: Immunohistochemical staining data indicated that KLF17 expression was significantly decreased in 98 of 158 gastric adenocarcinoma cases. Reduced KLF17 expression in fresh gastric cancer tissues was confirmed by Western blotting. Reduced expression of KLF17 was strongly correlated with tumor size, pN stage and lymphovascular invasion. Multivariate Cox regression analysis identified KLF17 expression as an independent prognostic factor for both overall survival (HR = 0.481, 95% CI = 0.225-0.665, p = 0.009) and disease-free survival (HR = 0.438, 95% CI = 0.254-0.758, p = 0.003). CONCLUSION: The reduced expression of KLF17 protein in gastric cancer was correlated with tumor size, pN stage and lymphovascular invasion and was an independent predictor for poor survival in patients undergoing surgery for gastric cancer.

Single nucleotide polymorphisms of PIN1 promoter region and cancer risk: evidence from a meta-analysis.

BACKGROUND: Peptidylprolyl cis/trans isomerase NIMA-interacting 1 (PIN1) is involved in the process of tumorigenesis. The two single nucleotide polymorphisms (-677T>C, -842G>C) in the PIN1 promoter region have been suspected of being associated with cancer risk for years, but the conclusion is still inconclusive. METHODS: Eligible case-control studies were retrieved by searching databases and references of related reviews and studies. Genotype distribution data, adjusted odds ratios (ORs) and 95% confidence (CIs) intervals were extracted to calculate pooled ORs. RESULTS: A total of 4619 cancer cases and 4661 controls were included in this meta-analysis. Overall, the PIN1 -667T>C polymorphism was not associated with cancer risk, while the -842C allele was significantly associated with reduced cancer risk (CC+GC vs. GG, OR = 0.725, 95% CI: 0.607-0.865; P(heterogeneity) = 0.012 and GC vs. GG: OR = 0.721, 95% CI: 0.591-0.880; P(heterogeneity) = 0.003). Results from genotype distribution data were in agreement with those calculated with adjusted ORs and 95% CIs. No publication bias was detected. CONCLUSIONS: Results of this meta-analysis suggest that the PIN1 -842G>C polymorphism is associated with decreased cancer risk, but that the -667T>C polymorphism is not.

[Effect of enteral nutrition via jejunostomy catheter on quality of life in gastric cancer patients who have undergone gastrectomy].

OBJECTIVE: To study the effect of enteral nutrition via jejunostomy catheter on the quality of life in gastric cancer patients who have undergone gastrectomy. METHODS: We retrospectively analyzed clinical data of 104 consecutive patients who had undergone curative resection for gastric cancer in Peking Union Medical College Hospital in 2011.All data were obtained from a prospectively maintained database of gastric cancer.The quality of life was compared between jejunostomy tube group(n=49)and tube-free group(n=55). RESULTS: The two groups were matched in gender,age,tumor size,tumor location,histological type,pTNM stage,type of surgery,body mass index(BMI),quality of life scales,and cycles of postoperative adjuvant chemotherapy(all P>0.05).Also,the global health status(P=0.154),physical function score(P=0.321),role function score(P=0.492),and fatigue symptom score(P=0.845)were not significantly different between these two groups one month after surgery.Three and 6 months after the surgery,patients in the jejunostomy tube group had significantly higher overall health status scores( P<0.001,P=0.038),physical function scores(P=0.004,P=0.005),and role function scores(P=0.002,P=0.038)and significantly lower fatigue symptom scores(P=0.020,P=0.043)when compared to patients from tube-free group. CONCLUSION: Enteral nutrition via jejunostomy catheter can improve the quality of life of gastric cancer patients who have undergone gastrectomy.

Digoxin downregulates NDRG1 and VEGF through the inhibition of HIF-1α under hypoxic conditions in human lung adenocarcinoma A549 cells.

Digoxin, an inhibitor of Na+/K+ ATPase, has been used in the treatment of heart-related diseases (such as congestive heart failure and atrial arrhythmia) for decades. Recently, it was reported that digoxin is also an effective HIF-1α inhibitor. We investigated whether digoxin could suppress tumor cell growth through HIF-1α in non-small cell lung cancer cells (A549 cells) under hypoxic conditions. An MTT assay was used to measure cell viability. RT-PCR and western blotting were performed to analyze the mRNA and protein expression of VEGF, NDRG1, and HIF-1α. HIF-1α nuclear translocation was then determined by EMSA. Digoxin was found to inhibit the proliferation of A549 cells under hypoxic conditions. Our results showed that hypoxia led to the upregulation of VEGF, NDRG1, and HIF-1α both at the mRNA and protein levels. We also found that the hypoxia-induced overexpression of VEGF, NDRG1, and HIF-1α was suppressed by digoxin in a concentration-dependent manner. As expected, our EMSA results demonstrated that under hypoxic conditions HIF-1α nuclear translocation was also markedly reduced by digoxin in a concentration-dependent manner. Our results suggest that digoxin downregulated hypoxia-induced overexpression of VEGF and NDRG1 at the transcriptional level probably through the inhibition of HIF-1α synthesis in A549 cells.