All-trans retinoic acid suppressed GES-1 cell proliferation induced by exosomes from patients with precancerous lesions by arresting the cell cycle in S-phase.

We aimed to detect the expression of specific LncRNAs in exosomes isolated from the serum of patients with precancerous lesions and to study the effect of these serum exosomes on the activity of GES-1 cells in patients with precancerous lesions, as well as the activity of all-trans retinoic acid on GES-1 cells with or without the exosomes. Exosomes were extracted from the serum of patients with precancerous lesions and normal controls. Based on our previous sequencing results, quantitative real time-PCR was used to detect differentially expressed LncRNAs. Exosomes from the serum of patients with precancerous lesions were cocultured with GES-1 cells, and 5 µM all-trans retinoic acid was added as an intervention. Changes in cell viability and expression of LncHOXA10 were observed. Compared with the blank group, the proliferation activity of GES-1 cells cocultured with exosomes derived from the serum of patients with precancerous lesions was increased (P < 0.01), the proportion of cells in S phase was increased (P < 0.05). After adding 5 µM all-trans retinoic acid, the viability of cells decreased significantly (P < 0.01), the proportion of cells in S phase decreased significantly (P < 0.05). The expression of LncHOXA10 was decreased (P < 0.05). All-trans retinoic acid can conduct its chemopreventive effects by inhibiting the expression of LncHOXA10, thereby reducing the activity of LncHOXA10 in GES-1 cells cocultured with serum exosomes from patients with precancerous lesions.

All-Trans Retinoic Acid Rescues the Tumor Suppressive Role of RAR-ß by Inhibiting LncHOXA10 Expression in Gastric Tumorigenesis.

Numerous long noncoding RNAs (LncRNAs) were having recently been shown to be involved in cancer development, including gastric cancer (GC). However, the precise mechanism and treatments to target these molecules have rarely been studied. Thus, we aimed to investigate the function of LncHOXA10 in gastric tumorigenesis and targeted therapy. First, we measured the differences in LncHOXA10 and retinoic acid receptor ß (RAR-ß) levels in gastric cancer tissues and cell lines compared with those in noncancerous tissues and cell lines. We observed that LncHOXA10 was significantly upregulated in gastric cancer tissues and cell lines, whereas RAR-ß showed the opposite trend. Subsequently, loss and gain of LncHOXA10 cell lines were constructed to determine whether LncHOXA10 plays a role in gastric tumorigenesis. The results showed that LncHOXA10 promoted the proliferation, migration, and invasion of cells, whereas apoptosis was markedly inhibited. Subsequently, mechanistic investigations revealed that LncHOXA10 can repress RAR-ß expression and that all-trans retinoic acid (ATRA) can rescue the expression of RAR-ß. Finally, we showed that ATRA can reverse the pro-cancerous function of LncHOXA10. We showed that LncHOXA10 may be a prognostic and therapeutic factor of gastric cancer by negatively regulating RAR-ß. Furthermore, ATRA can inhibit the role of LncHOXA10 in gastric tumorigenesis.

Intention to response, emergency preparedness and intention to leave among nurses during COVID-19.

AIM: To comprehensively assess the current level and identify associated factors of intention to response and emergency preparedness of clinical nurses during COVID-19 outbreak. DESIGN: A cross-sectional study was designed. METHODS: Demographic and characteristic questionnaire, intention to response scale, emergency preparedness scale and a self-designed questionnaire related to effects of events and intention to leave were used in this study. RESULTS: The mean scores of intention to response and emergency preparedness were 82.00 (SD = 18.17) and 64.99 (SD = 12.94), respectively. Moral consideration, engaged in COVID-19 protection training, had working experience in SARS, and the other eight factors were explained 34.6% of the total model variance in intention to response model (F = 80.05, p < .001). While, the level of IR, whether the pace of work was affected and above three same factors were explained 21.5% of the total model variance (F = 91.05, p < .001). Pathway analysis revealed that moral consideration, intention to leave and impacts on work and life mediate the relationship between EP and IR.

Dietary Fat Intake and the Risk of Skin Cancer: A Systematic Review and Meta-Analysis of Observational Studies.

We conducted a meta-analysis to evaluate the association between fat intake and the risk of three major types of skin cancer including basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and cutaneous malignant melanoma (CMM). A comprehensive search of PubMed and EMBASE was performed to identify all relevant observational studies published up to December 1, 2018. Specific odds ratio (OR) or relative risk (RR) estimates for the highest versus the lowest intake of dietary fat and 95% confidence intervals (CI) from the included studies were pooled using random effect model. Three prospective cohort studies (175,675 participants and 30,915 BCC cases, 4,106 SCC cases and 1,638 CMM cases) and nine case-control studies (328 BCC cases, 493 SCC cases, 1,547 CMM cases and 2,660 controls) were identified. The pooled results indicated that dietary consumption of total fat and saturated fat were not associated with three major types of skin cancer. High consumption of monounsaturated fat was significantly associated with a decreased risk of BCC (RR: 0.90, 95% CI: 0.85-0.96) and high level of polyunsaturated fat intake was potentially positively associated with SCC (RR: 1.19, 95% CI: 1.06-1.33). Our findings should be confirmed by further evidence from well-designed and large-scale prospective cohort studies.

The effect of Chinese famine exposure in early life on dietary patterns and chronic diseases of adults.

OBJECTIVE: To assess the effect of famine exposure during early life on dietary patterns, chronic diseases, and the interaction effect between famine exposure and dietary patterns on chronic diseases in adulthood. DESIGN: Cross-sectional study. Dietary patterns were derived by factor analysis. Multivariate quantile regression and log-binomial regression were used to evaluate the impact of famine exposure on dietary patterns, chronic diseases and the interaction effect between famine exposure and dietary patterns on chronic diseases, respectively. SETTING: Hefei, China. PARTICIPANTS: Adults aged 45-60 years (n 939). RESULTS: 'Healthy', 'high-fat and high-salt', 'Western' and 'traditional Chinese' dietary patterns were identified. Early-childhood and mid-childhood famine exposure were remarkably correlated with high intake of the traditional Chinese dietary pattern. Compared with the non-exposed group (prevalence ratio (PR); 95 % CI), early-childhood (3·13; 1·43, 6·84) and mid-childhood (2·37; 1·05, 5·36) exposed groups showed an increased PR for diabetes, and the early-childhood (2·07; 1·01, 4·25) exposed group showed an increased PR for hypercholesterolaemia. Additionally, relative to the combination of non-exposed group and low-dichotomous high-fat and high-salt dietary pattern, the combination of famine exposure in early life and high-dichotomous high-fat and high-salt dietary pattern in adulthood had higher PR for diabetes (4·95; 1·66, 9·05) and hypercholesterolaemia (3·71; 1·73, 7·60), and significant additive interactions were observed. CONCLUSIONS: Having suffered the Chinese famine in childhood might affect an individual's dietary habits and health status, and the joint effect between famine and harmful dietary pattern could have serious consequences on later-life health outcomes.

Prognostic value of the expression of cancer stem cell-related markers CD133 and CD44 in hepatocellular carcinoma: From patients to patient-derived tumor xenograft models.

High expression of cancer stem cell (CSC) markers is related to poor prognosis of patients with hepatocellular carcinoma (HCC). However, the expression of these markers in patient-derived xenograft (PDX) models and the relationship of the expression levels of these markers between HCC patients and their PDX models at subsequent low passages are unclear. To investigate the prognostic impact of putative CSC markers in patients with HCC and in related PDX models, the expression of CD133, CD90, CD44, ALDH1, CK7, CK19, OCT4, SOX2, vimentin, nestin, CD13 and EpCam were assessed by quantitative reverse transcription-PCR (qRT-PCR) and then were validated using immunohistochemistry in tumor or peritumoral tissues from patients and tumor tissues from PDX models. Cumulative survival analysis of the patients and animals was conducted using the Kaplan-Meier method and the log-rank test. Only the expression levels of CD133 and CD44 were higher in tumor tissues than in the peritumoral tissues of HCC patients by qRT-PCR. High consistency of the prognostic value of the expression of CD133/CD44 was observed in HCC patients and the PDX models. High expression levels of CD133 and CD44 were positively related to the poor prognosis of HCC patients and to that in the PDX models. PDX HCC models in the present study have been suggested to be predictive of disease outcome, which could shed light on personalized medicine and the mechanisms of CSC marker expression on prognosis.

Physiological and behavioral responses in offspring mice following maternal exposure to sulfamonomethoxine during pregnancy.

Sulfamonomethoxine (SMM), a veterinary antibiotic, is widely used in China. However, the impacts of maternal SMM exposure on neurobehavioral development in early life remain little known. In this study, we investigated the effects of maternal SMM exposure during pregnancy on behavioral and physiological responses in offspring mice. Pregnant mice were randomly divided into three SMM-treated groups, namely low-(10mg/kg/day), medium-(50mg/kg/day), and high-dose (200mg/kg/day), and a control group. The pregnant mice in the SMM-treated groups received SMM by gavage daily from gestational day 1-18, whereas those in the control received normal saline. On postnatal day (PND) 50, spatial memory was assessed using the Morris water maze test, and anxiety was measured using the elevated plus-maze and open field tests. The results showed significantly increased blood glucose in pups whose mothers received a high SMM dose. In addition, maternal SMM exposure increased anxiety-related activities among the offspring; spatial learning and memory were impaired more severely in the male offspring. The contents of tetrahydrobiopterin (BH4) and brain-derived neurotrophic factors (BDNF) on PND 22 were significantly reduced in the male offspring of the high-dose group compared with the controls. These findings indicate that SMM may be identified as a risk factor for cognitive and behavioral development on the basis of gender and that it may be associated with diminished BH4 and BDNF levels early in life.

A new mode of community continuing care service for COPD patients in China: participation of respiratory nurse specialists.

OBJECTIVE: This study explored a community nursing service mode in which respiratory nurse specialists cared for patients with chronic obstructive pulmonary disease (COPD) in a 12-week period after hospital discharge, with the aim of better preventing acute exacerbations, improving health-related quality of life (HRQOL) and reducing medical expenses in these patients. METHODS: We carried out a prospective randomized controlled study in which 68 COPD patients discharged were recruited from a general hospital in Guangzhou, China, were randomized divided into two groups. The control group underwent conventional nursing care, and the intervention group received community continuing care by respiratory nurse specialists. The observation period was 12 weeks. The results of intervention were evaluated using the Seattle Obstructive Lung Disease Questionnaire (SOLDQ) and the COPD Self-Efficacy Scale (CSES). In addition, the frequency of acute exacerbations, emergency treatments or hospitalizations, and medical expenses were recorded in the 12-week observation period. RESULTS: After six weeks, the total and subscale scores (P < 0.05) of SOLDQ and CSES significantly improved compared to the baseline ones in the intervention group. The control group had significantly higher scores in the treatment satisfaction (TS) of SOLDQ, the total score, and the weather/environment and behavioral risk factors of CSES. After 12 weeks, the total and subscale scores of SOLDQ and CSES showed a sustained and significant growth in the intervention group (P < 0.05). The control group had significantly higher scores only in the weather/environment risk factor of CSES. During the 12-week observation, the intervention group had significantly fewer acute exacerbations, emergency treatments or re-hospitalizations and significantly lower average medical expenses than the control group (P < 0.05). CONCLUSIONS: Community continuing care by respiratory nurse specialists may improve HRQOL, increase self-efficacy, reduce incidence of acute exacerbation, and lower medical expenses in patients with COPD after hospital discharge.

Plasma and tissue free amino acid profiles and their concentration correlation in patients with lung cancer.

Variation of plasma free amino acids (PFAAs) is an essential feature of protein metabolic abnormalities in cancer patients. But there still little data about the cancer tissue free amino acid (TFAAs) profiles, including their patterns and correlations with PFAAs. To evaluate the variation in PFAAs and cancer TFAAs in patients with lung cancer, including their patterns and correlations, we investigated the concentrations of free amino acids in lung cancer tissues (n=27), paired lung paracarcinomous tissues (n=27) and plasma (n=27) using an automatic amino acid analyzer after pre-treatment. Within the PFAAs, the concentrations of five amino acids (tryptophan, glycine, citrulline, ornithine and proline) were significantly decreased, while that of phenylalanine was markedly increased compared with control subjects. Within the TFAAs, the concentrations of three amino acids (taurine, glutamic acid and glycine) were increased, while the concentrations of two amino acids (lysine and ornithine) were decreased significantly in lung cancer tissues compared with the paracarcinomous tissues. The amino acid patterns in PFAAs and TFAAs had similar trends, but percentage variations were diverse. Additionally, the concentrations of five amino acids (lysine, phenylalanine, threonine, serine, and alanine) in PFAAs correlated with those in lung cancer TFAAs, but no amino acids in PFAAs were correlated with those in lung paracarcinomous TFAAs. Thus, PFAA profiles may reflect the status of cancer tissues, which may provide more information about the metabolic statuses and prognoses of patients with lung cancer.

The mRNA of human cytoplasmic arginyl-tRNA synthetase recruits prokaryotic ribosomes independently.

There are two isoforms of cytoplasmic arginyl-tRNA synthetase (hcArgRS) in human cells. The long form is a component of the multiple aminoacyl-tRNA synthetase complex, and the other is an N-terminal truncated form (NhcArgRS), free in the cytoplasm. It has been shown that the two forms of ArgRS arise from alternative translational initiation in a single mRNA. The short form is produced from the initiation at a downstream, in-frame AUG start codon. Interestingly, our data suggest that the alternative translational initiation of hcArgRS mRNA also takes place in Escherichia coli transformants. When the gene encoding full-length hcArgRS was overexpressed in E. coli, two forms of hcArgRS were observed. The N-terminal sequencing experiment identified that the short form was identical to the NhcArgRS in human cytoplasm. By constructing a bicistronic system, our data support that the mRNA encoding the N-terminal extension of hcArgRS has the capacity of independently recruiting E. coli ribosomes. Furthermore, two critical elements for recruiting prokaryotic ribosomes were identified, the "AGGA" core of the Shine-Dalgarno sequence and the "A-rich" sequence located just proximal to the alternative in-frame initiation site. Although the mechanisms of prokaryotic and eukaryotic translational initiation are distinct, they share some common features. The ability of the hcArgRS mRNA to recruit the prokaryotic ribosome may provide clues for shedding light on the mechanism of alternative translational initiation of hcArgRS mRNA in eukaryotic cells.

Potential health risks of heavy metals in cultivated topsoil and grain, including correlations with human primary liver, lung and gastric cancer, in Anhui province, Eastern China.

Environmental exposure to heavy metals is a well-known risk factor for cancers. To evaluate potential health risks of heavy metals (Cr, Cd, Pb, As and Hg) and Se in cultivated topsoil and grains, we investigated the concentrations of Hg, As and Se using atomic fluorescence spectrometry and Cr, Cd and Pb using inductive coupled plasma emission spectrometry (ICP-MS). We also analyzed human cancer tissues for heavy metals. Potential health risks for local residents were evaluated by calculating the hazard index (HI) and the total carcinogenic risk (TCR) for soil heavy metals and the target hazard quotient (THQ) and the carcinogenic risk (CR) for grain heavy metals. A bioconcentration factor (BCF) was applied to quantify the bioaccumulation of heavy metals. Our results demonstrated that the mean concentrations of heavy metals in soil were all within the safety limits set by FAO/WHO and Chinese regulations; however, the mean concentrations of Cr and Hg in grain exceeded the safety limits. HI and TCR for soil heavy metals were all within acceptable levels, but the THQ for four grain heavy metals exceeded the target value of 1 (Cr, 2.64; Pb, 1.41; As, 1.24; Hg, 1.07; Cd, 0.39). The grain CR for Cr, Pb and As exceeded the accepted risk level of 10(-6). BCF values indicated that the bioaccumulation capacity decreased in the following sequence: Hg>Se>Cd>Cr>Pb>As. We also observed statistically significant correlations of topsoil Pb concentration with human gastric cancer and grain Hg with human liver cancer. Therefore, long-term low dose exposure of heavy metals may play a key role in tumorigenesis, and it may not be necessary to accumulate a high concentration of heavy metals in the human body for those metals to induce tumorigenesis.

[Impact of oral vitamin D supplementation in early life on diabetic mice induced by streptozotocin].

OBJECTIVE: To evaluate the effect of oral vitamin D supplementation in early life on blood glucose, insulin content, diabetes incidence, and histomorphology in pancreatic islet induced by streptozotocin. METHODS: Three-week-old C57BL/6 mice were given either control diet (American Institute of Nutrition [AIN]-93G), or three different dose of vitamin D-supplemented diet. Nine weeks after dietary intervention, C57BL/6 mice were treated with streptozotocin i.p. for 5 consecutive days. After injection of STZ, The fasting blood glucose and diabetes incidence was tested once a week. The insulin content, histomorphology in pancreatic islets was conducted at the end of experiments. RESULTS: (1) Vitamin D supplementation in early life can decrease the fasting blood glucose values induced by STZ, and the decreases effect of high dose vitamin D-supplemented group is the most significant (P<0.01). (2) Vitamin D supplementation in early life can prevent diabetes incidence, and the decreases effect of high dose vitamin D-supplemented group is the most significant, fully suppress the onset of diabetes about four weeks later after injected by STZ (P<0.01). (3) As compared to the control group, insulin content in medium and high dose vitamin D-supplemented groups were significantly up-regulated after injection of STZ (P<0.05), and the effect of high dose vitamin D-supplemented group is the most significant. (4) The damage of pancreatic islets induced by STZ was clearly restored in medium and high dose vitamin D-supplemented groups, and effect of high dose vitamin D-supplemented group is the most significant. CONCLUSION: Oral vitamin D supplementation in early life can decrease the fasting blood glucose values, prevent diabetes incidence, up-regulate insulin content, restored the damage of pancreatic islets induced by STZ, and effects of high dose vitamin D-supplementde group are all the most significant.

Human cytoplasmic ProX edits mischarged tRNAPro with amino acid but not tRNA specificity.

aaRSs (aminoacyl-tRNA synthetases) are responsible for ensuring the fidelity of the genetic code translation by accurately linking a particular amino acid to its cognate tRNA isoacceptor. To ensure accuracy of protein biosynthesis, some aaRSs have evolved an editing process to remove mischarged tRNA. The hydrolysis of the mischarged tRNA usually occurs in an editing domain, which is inserted into or appended to the main body of the aaRS. In addition, autonomous, editing domain-homologous proteins can also trans-edit mischarged tRNA in concert or in compensating for the editing function of its corresponding aaRS. The freestanding ProX is a homologue of the editing domain of bacterial ProRS (prolyl-tRNA synthetase). In the present study, we cloned for the first time a gene encoding HsProX (human cytoplasmic ProX) and purified the expressed recombinant protein. The catalytic specificity of HsProX for non-cognate amino acids and identity elements on tRNAPro for editing were also investigated. We found that HsProX could deacylate mischarged Ala-tRNAPro, but not Cys-HstRNA(UGGPro), and specifically targeted the alanine moiety of Ala-tRNAPro. The importance of the CCA76 end of the tRNA for deacylation activity and key amino acid residues in HsProX for its editing function were also identified.

[Influence of different dietary patterns on bone mineral density and body mass index of college freshmen in urban and rural areas of China].

OBJECTIVE: To find out the differences of dietary patterns among freshmen coming from urban and rural areas that might have influenced their bone mineral density and body mass index (BMI). METHODS: With stratified random sampling method, dietary patterns and their bone mineral density, BMI of 1319 freshmen were studied. RESULTS: (1) The ratios of urban freshmen who chose "western food" pattern (χ(2) = 31.548, P = 0.000; χ(2) = 13.068, P = 0.001), "animal food" pattern (χ(2) = 8.279, P = 0.016; χ(2) = 41.137, P = 0.000) or "calcium food" pattern (χ(2) = 37.254, P = 0.000; χ(2) = 15.651, P = 0.000) were higher than that of rural freshmen, and the ratios of rural freshmen who chose "Chinese traditional" pattern (χ(2) = 36.194, P = 0.000; χ(2) = 25.936, P = 0.000) were higher than that of urban freshmen. (2) The average height, weight, BMI, speed of sound (SOS) of male freshmen from rural areas were lower than that from the city and the differences were statistically significant (P < 0.05). Among those female freshmen, only height and weight were significantly different (P < 0.05). (3) In both rural and urban freshmen, the factor scores of "western food" pattern had a positive correlation with BMI, with the correlation coefficients as 0.187, 0.192, 0.551, 0.465 (P < 0.001). The factor scores of "calcium food" pattern were positively related to bone mineral density (SOS values) with correlation coefficients as 0.680, 0.342, 0.841, 0.786, P < 0.001 respectively. The factor scores on "Chinese traditional" pattern were negatively correlated with BMI, with correlation coefficients as -0.223, -0.093 (P < 0.05) which were positively related to bone mineral density (SOS values) in both rural and urban male freshmen, with correlation coefficients as 0.905, 0.711 (P < 0.001). CONCLUSION: Different dietary patterns chosen by urban and rural freshmen had a significant impact on both bone mineral density and BMI.

Role of tRNA amino acid-accepting end in aminoacylation and its quality control.

Aminoacyl-tRNA synthetases (aaRSs) are remarkable enzymes that are in charge of the accurate recognition and ligation of amino acids and tRNA molecules. The greatest difficulty in accurate aminoacylation appears to be in discriminating between highly similar amino acids. To reduce mischarging of tRNAs by non-cognate amino acids, aaRSs have evolved an editing activity in a second active site to cleave the incorrect aminoacyl-tRNAs. Editing occurs after translocation of the aminoacyl-CCA76 end to the editing site, switching between a hairpin and a helical conformation for aminoacylation and editing. Here, we studied the consequence of nucleotide changes in the CCA76 accepting end of tRNA(Leu) during the aminoacylation and editing reactions. The analysis showed that the terminal A76 is essential for both reactions, suggesting that critical interactions occur in the two catalytic sites. Substitutions of C74 and C75 selectively decreased aminoacylation keeping nearly unaffected editing. These mutations might favor the regular helical conformation required to reach the editing site. Mutating the editing domain residues that contribute to CCA76 binding reduced the aminoacylation fidelity leading to cell-toxicity in the presence of non-cognate amino acids. Collectively, the data show how protein synthesis quality is controlled by the CCA76 homogeneity of tRNAs.

A unique insertion in the CP1 domain of Giardia lamblia leucyl-tRNA synthetase.

Leucyl-tRNA synthetase (LeuRS) catalyzes the esterification of the tRNA(Leu) isoacceptor with leucine. It contains a large insertion domain, connective peptide 1 (CP1), for amino acid editing. Here, we cloned the gene encoding LeuRS from Giardia lamblia (GlLeuRS), one of the most ancient eukaryotes. GlLeuRS was purified from an Escherichia coli overproduction strain, and its properties were investigated. The isolated CP1 domain of GlLeuRS (GlLeuRS-CP1) was an active protein for editing mischarged G. lamblia tRNA(Leu)(AAG) (GltRNA(Leu)). Insertion of 49 amino acid residues within the CP1 domain (the so-called 49-amino acid motif) was important for the optimal aminoacylation activity of GlLeuRS and was crucial for the editing capacity of GlLeuRS-CP1. Additionally, the motif can confer editing activity on the editing-defective isolated CP1 domain from E. coli LeuRS (EcLeuRS-CP1). We also found that GlLeuRS could not rescue a Saccharomyces cerevisiae leuS null strain, suggesting different recognition modes for these two LeuRSs with respect to tRNA(Leu).