Helicobacter pylori upregulates circPGD and promotes development of gastric cancer.

PURPOSE: Helicobacter pylori (H. pylori) has unique biochemical traits and pathogenic mechanisms, which make it a substantial cause of gastrointestinal cancers. Circular RNAs (circRNAs) have concurrently been identified as an important participating factor in the pathophysiology of several different cancers. However, the underlying processes and putative interactions between H. pylori and circRNAs have received very little attention. To address this issue, we explored the interaction between H. pylori and circRNAs to investigate how they might jointly contribute to the occurrence and development of gastric cancer. METHODS: Changes in circPGD expression in H. pylori were detected using qRT-PCR. Cell proliferation and migration changes were assayed by colony formation, the CCK-8 assay and the transwell assay. Apoptosis was measured by flow cytometry. Western blot was conducted to detect changes in cell migration, apoptosis, proliferation and inflammation-associated proteins. QRT-PCR was used to measure changes in circPGD and inflammation-associated factors. RESULTS: We found that H. pylori induced increased circPGD expression in infected human cells and facilitated gastric cancer progression in three ways by promoting cell proliferation and migration, enhancing the inflammatory response, and inhibiting apoptosis. CONCLUSIONS: CircPGD appears to play a role in H. pylori-related gastric cancer and may thus be a viable, novel target for therapeutic intervention.

Assessment of the cultivated land quality in the black soil region of Northeast China based on the field scale.

In some developing countries, particularly China, a significant number of individual farmers manage small field scale of cultivated land. However, the existing research on cultivated land quality assessment mainly focuses on large-scale regions, establishing comprehensive index systems from a macro perspective, while lacking evaluations customized to individual farmers, who constitute a crucial component in agricultural production, and a demand-driven field-scale assessment of cultivated land quality. Therefore, we developed a field-scale index system that meets the needs of individual farmers in the black soil region of Northeast China. Additionally, we proposed a machine learning model for field-scale cultivated land quality assessment. The experimental results showed that our model achieved an [Formula: see text] value of 0.9660 and an [Formula: see text] of [Formula: see text] under fourfold cross-validation, which represents an improvement of 5.19% and a reduction of 1.13%, respectively, relative to the XGBoost model. Ultimately, we conducted obstacle factor diagnosis, aiming to assist individual farmers in identifying the existing issues in their cultivated land fields. This study not only provides guidance to individual farmers but also addresses the research gap in cultivated land quality assessment by offering an individual farmer demand-driven index system for field-scale studies.

CircRNA_15430 reduced by Helicobacter pylori infection and suppressed gastric cancer progression via miR-382-5p/ZCCHC14 axis.

BACKGROUND: Helicobacter pylori (H.pylori, HP) is one of the main causes of gastric cancer (GC). CircRNAs have been reported to play a crucial role in developing many types of cancer. However, the role of circRNAs in the development and progression of HP infected-GC has not been studied. METHODS: The location of circRNA_15430 in GC cells were detected by nuclear and cytoplasmic RNA fractionation and RNA fluorescence in situ hybridization analysis (FISH) assays, and circRNA_15430, miR-382-5p and ZCCHC14 expression in GC cell lines and tissues were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The function of circRNA_15430 in GC cells were examined by using colony formation, cell counting kit-8 (CCK-8) and Transwell assays, flow cytometry and laser scanning confocal microscopy. The protein levels were detected by Western blotting. Whether circRNA_15430 sponges miR-382-5p was monitored with a dual-luciferase reporter assay. Furthermore, circRNA_15430 was analyzed in vivo in tumor growth with nude mice. RESULTS: CircRNA_15430 is primarily localized in the cytoplasm of GC cells, and downregulated in the GC cell lines and tissues, and is negatively correlated with the tumor size. Downregulation of circRNA_15430 promotes proliferation, migration and suppresses cell apoptosis and autophagy in GC cells. Mechanically, circRNA_15430 acts as a miR-382-5p sponge, alleviating the inhibitory effect of miR-382-5p on its target ZCCHC14. Knockdown circRNA_15430 enhances tumor growth in vivo. In addition, circRNA_15430 was reduced in HP + gastritis tissues and HP-infected MGC-803 cells, reversing the pro-HP effect on autophagy. Additionally, miR-382-5p was increased in HP + gastritis tissue and HP-infected MGC-803 cells while ZCCHC14 decreased in HP-infected MGC-803 cells. MiR-382-5p reverses the effect of si-ZCCHC14 on autophagosome numbers in MGC-803 cells. CONCLUSIONS: Therefore, circRNA_15430 plays an inhibitory role in GC and regulates the progression of HP infection-related GC, providing a novel molecular marker for GC therapy.

Low Expression of GIGYF1 Inhibits Metastasis, Proliferation, and Promotes Apoptosis and Autophagy of Gastric Cancer Cells.

GRB10 interacting GYF protein 1 (GIGYF1) binds to the N-terminal region of Grb10, regulates multiple signaling pathways. However, it is not clear what happens to cell proliferation, metastasis, apoptosis, and autophagy when the expression level of GIGYF1 gene is reduced. Detection of GIGYF1 expression in clinical tissue specimens and gastric cancer (GC) cell lines by quantitative Real-time PCR (qRT-PCR), GIGYF1 gene was knocked down in MGC-803 cells using small interfering RNA, the effect of GIGYF1 gene on cell metastasis was detected using Transwell assay and wound healing assay, the effect on cell proliferation was detected using plate cloning assay and cck-8 assay, the effect on apoptosis was detected using flow cytometry, autophagosomes were detected using laser confocal microscopy, and the effect on protein expression was detected using immunofluorescence and Western blotting. GIGYF1 gene expression was higher in tumor tissue samples than in paracancer tissue samples, and higher in human GC cell lines than in human normal gastric epithelial cells. GIGYF1 gene knockdown inhibited cell migration, scratch healing ability and EMT process, weakened cell proliferation ability, increased apoptosis rate, promoted the formation of autophagosomes, and changed the corresponding protein expression level. Meanwhile, GIGYF1 knockdowns inhibited the ERK and AKT signaling. In conclusion, the low expression of GIGYF1 gene can inhibit the occurrence and progression of gastric cancer, during which the ERK and AKT signaling pathways are inhibited.

Circular RNA circPGD contributes to gastric cancer progression via the sponging miR-16-5p/ABL2 axis and encodes a novel PGD-219aa protein.

CircRNAs have critical effects on tumor development and progression. However, circPGD effect on gastric cancer (GC) is still elusive. Nuclear and cytoplasmic RNA fractionation, and RNA-FISH assay examined the localization of circPGD in MGC-803 cells. qRT-PCR was conducted to detect the expression and prognostic significance of circPGD, miR-16-5p, and ABL2 within GC tissues. Meanwhile, qRT-PCR, luciferase reporter assays, rescue, and western blotting assays confirmed the interactions between circPGD, miR-16-5p, and ABL2. Transwell, wound healing, and colony-formation assays, as well as CCK-8 and cell apoptosis assays, analyzed the functions of circPGD, miR-16-5p, ABL2, as well as PGD-219aa within GC cells. Western blotting and cell immunofluorescence experiments detected the differences in the expression of the related proteins. Finally, xenograft and metastatic mouse models were used to investigate circPGD function in vivo. Mass spectrometry was used to detect the existence of PGD-219aa in MGC-803 cells. CircPGD was localized in the cytoplasm and nucleus of MGC-803 cells. Compared with the control, circPGD and ABL2 expression increased within GC tissues and cells, and the miR-16-5p level was decreased. Functionally, circPGD promoted cell proliferation, migration and suppressed apoptosis in vitro. Mechanistically, circPGD sponged miR-16-5p for relieving miR-16-5p suppression on the corresponding target ABL2 via the SMAD2/3 and YAP signaling pathways. In addition, circPGD encodes a novel PGD-219aa protein that can enhance the growth and migration of GC cells, while inhibiting GC cells apoptosis via the SMAD2/3 and YAP signaling pathways. Furthermore, circPGD overexpression enhanced tumor aggressiveness, while circPGD knockdown inhibited tumor growth. Overall, circPGD has a novel oncogenic effect on GC cells, indicating the potential of circPGD as the tumorigenic factor and a promising diagnostic marker for GC.

High expression of ANRIL correlated with the poor prognosis in patients with cancer: A meta-analysis.

BACKGROUND: ANRIL, also called CDKN2B antisense RNA 1, is an important genetic susceptibility locus for cardiovascular diseases and associated with numerous pathologies, including several human cancers. OBJECTIVE: The relationship between ANRIL and the clinical outcome or prognosis of cancer patients was analyzed in this meta-analysis. METHODS: One thousand seven hundred eight cancer patients were selected in 23 studies from 3 databases (Pubmed, Cochrane Library, and EMBASE). RESULTS: A fixed-effects model indicated that the high expression of ANRIL is obviously linked to poor overall survival (OS) (Hazard ratio [HR] = 1.77, 95% confidence interval [CI] = 1.57-2.00, P < .00001); the random-effects model revealed poor disease-free survival (DFS) (HR = 1.86, 95% CI: 1.46-2.37, P < .00001). A high level of ANRIL expression was also associated with the tumor size (small vs large, odds ratio [OR] = 0.57, 95% CI: 0.39-0.83, P = .003), TNM stage (I + II vs III + IV; OR = 0.40, 95% CI: 0.24-0.69, P = .0008), and lymph node metastasis (LNM) (Yes vs No, OR = 3.66, 95% CI: 1.46-9.17, P = .006). ANRIL was not related significantly to histologic differentiation compared to poor with moderate + well; the OR value is 0.74, 95% CI: 0.26-2.12, P = .58. In addition, evidence suggested that a high level of ANRIL was positively associated with human cancer type, follow-up time, and sample size. CONCLUSION: This meta-analysis demonstrated that ANRIL may be a valuable biomarker for predicting poor prognosis in cancer patients.

Helicobacter pylori promotes gastric cancer progression through the tumor microenvironment.

Gastric cancer (GC) is a leading type of cancer. Although immunotherapy has yielded important recent progress in the treatment of GC, the prognosis remains poor due to drug resistance and frequent recurrence and metastasis. There are multiple known risk factors for GC, and infection with Helicobacter pylori is one of the most significant. The mechanisms underlying the associations of H. pylori and GC remain unclear, but it is well known that infection can alter the tumor microenvironment (TME). The TME and the tumor itself constitute a complete ecosystem, and the TME plays critical roles in tumor progression, metastasis, and drug resistance. H. pylori infection can act synergistically with the TME to cause DNA damage and abnormal expression of multiple genes and activation of signaling pathways. It also modulates the host immune system in ways that enhance the proliferation and metastasis of tumor cells, promote epithelial-mesenchymal transition, inhibit apoptosis, and provide energy support for tumor growth. This review elaborates myriad ways that H. pylori infections promote the occurrence and progression of GC by influencing the TME, providing new directions for immunotherapy treatments for this important disease. KEY POINTS: • H. pylori infections cause DNA damage and affect the repair of the TME to DNA damage. • H. pylori infections regulate oncogenes or activate the oncogenic signaling pathways. • H. pylori infections modulate the immune system within the TME.

The significant prognostic value of ZEB1-AS1 up-regulation in patients with cancer.

Zinc finger E-box binding homeobox 1 antisense 1 (ZEB1-AS1) is a long non-coding RNA, which has found to unregulated in various kinds of cancer. This meta-analysis was conducted to demonstrate the association between ZEB1-AS1 expression levels and clinical outcome or prognosis of cancer patients.10 studies with 783 cancer patients were included in this meta-analysis by retrieving 5 databases (PubMed Central, EMBASE, Cochrane Library, Wiley Online Library and Medline).The result showed that overexpression of ZEB1-AS1 is significantly correlated with poor OS (Hazard ratio, HR=2.45, 95% confidence interval, CI: 1.89-3.16). ZEB1-AS1 expression levels were also associated with clinicopathological parameters including lymph node metastasis (Yes vs. No; OR=4.00, 95%CI: 2.23-7.17, P<0.00001), histologic differentiation (Moderate + poor vs. Well; OR=2.72, 95% CI: 1.69-4.37, p<0.0001), tumor metastasis and invasion (Yes vs. No; OR =2.52, 95%CI: 1.12-5.68, P=0.03) and TNM stage (III+IV vs. I+II; OR=2.76, 95 %CI 1.46-5.21, P=0.002). However, ZEB1-AS1 expression was not significantly associated with patients' gender (Male vs. Female; OR=1.20, 95% CI: 0.87-1.66; P=0.27).This meta-analysis indicated the potential value of ZEB1-AS1 as a biomarker for predicting a poor prognosis in patients with cancer.

High Expression of ABL2 Suppresses Apoptosis in Gastric Cancer.

BACKGROUND: Diseases associated with Abelson-related gene (also called ABL2) include leukemia; furthermore, previous researches have studied the expressions and functions of ABL2 in different types of malignancies and found that it plays an important role in almost all kinds of cancers. AIMS: Nevertheless, the mechanism of ABL2 in gastric cancer (GC) remains vague. METHODS: In the present study, the level of ABL2 in human GC tissues was detected by immunohistochemistry. Also, the GC cell lines MGC-803 and BGC-823 were selected to stably knock down and overexpress the level of ABL2 by corresponding lentiviral vectors. Puromycin was used to maintain the stable low expression of ABL2 MGC-803 cells compared with control cells; what is more, the high expression of ABL2 BGC-823 cells was also obtained. Based on it, we detected the proteins associated with apoptosis, such as Bcl-2 family and caspase family by western blotting. RESULTS: The most appropriate concentration of puromycin to kill GC cells is 1 µg/mL; then, we obtained the corresponding stable cell lines. Furthermore, we found that high level of ABL2 in BGC-823 cells increased the expression of Bcl-XL, total PARP, and caspase3, while decreased the level of cleaved caspase3 and cleaved caspase9. Consistent results are received in MGC-803 cells. In addition, ABL2 overexpression led to the protein related with Ras/Erk and PI3K/AKT signaling pathway increased; also, we found that the major proteins play a significant role in it. CONCLUSION: All the data showed that high expression of ABL2 suppresses apoptosis through Ras/Erk and PI3K/AKT signaling pathway in GC cell lines.

Preliminary study and bioinformatics analysis on the potential role of CagQ in type IV secretion system of H.pylori.

Helicobacter pylori (H.pylori), is a major causative agent of chronic gastritis, gastric carcinoma and duodenal ulcer. Remarkably, H.pylori carries cytotoxin-associated gene pathogenicity island (CagPAI) which encodes a type IV secretion system (T4SS). T4SS is capable of forming a syringe-like structure to deliver oncoprotein cytotoxin-associated Antigen (CagA) into gastric epithelial cells and resulting in a cascade of events in host cells, such as induction of pro-inflammatory cytokines, alteration of cellular gene expression and cytoskeletal rearrangements. Among of those proteins in T4SS, CagQ still remains unknown functions. In this study, we performed analysis of protein-protein interaction and revealed that CagQ correlated with the most virulence factor CagA in T4SS. Interestingly, our data demonstrated that CagQ-deficient mutant strain had significantly lower expression in both mRNA and protein levels of CagA compared with H.pylori wild-type strain 26695. Moreover, we demonstrated that CagQ deletion also played a vital role in suppressing CagA-induced apoptosis of host gastric epithelial cells. To further investigate the role of CagQ in T4SS, we used bioinformatics analysis to provide a preliminary insight into CagQ. These results showed that CagQ possessed a transmembrane region from amino acid 50-68 which is also consistent with the prediction of hydrophobic scale and structure modeling. Thus, we conclude that CagQ is a membrane protein in T4SS and is crucial for maintaining CagA expression and CagA-induced apoptotic effects. This provides a novel specific therapeutic target for H.pylori CagA-induced gastroduodenal diseases.

Awareness Status of Chronic Disabling Neurological Diseases among Elderly Veterans.

BACKGROUND: The awareness, treatment and prevention of chronic diseases are generally poor among the elderly population of China, whereas the prevention and control of chronic diseases in elderly veteran communities have been ongoing for more than 30 years. Therefore, investigating the awareness status of chronic disabling neurological diseases (CDND) and common chronic diseases (CCD) among elderly veterans may provide references for related programs among the elderly in the general population. METHODS: A cross-sectional survey was conducted among veterans ≥60 years old in veteran communities in Beijing. The awareness of preventive strategies against dementia, Alzheimer's disease (AD), Parkinson's disease (PD), sleep disorders, cerebrovascular disease (CVD) and CCD such as hypertension, and the approaches used to access this information, including media, word of mouth (verbal communication among the elderly) and health care professionals, were investigated via face-to-face interviews. RESULTS: The awareness rates for CCD and CVD were approximately 100%, but that for AD was the lowest at <10%. The awareness rates for sleep disorders, PD and dementia, were 51.0-89.4%. Media was the most commonly selected mode of communication by which veterans acquired knowledge about CCD and CVD. Media was used by approximately 80% of veterans. Both health care professionals and word of mouth were used by approximately 50% of veterans. With respect to the source of information about CDND excluding AD, the rates of the use of health care professionals, word of mouth and media were 10.6-28.2%, 56.5-76.5%, and approximately 50%, respectively. CONCLUSIONS: The awareness of CDND among elderly veterans was significantly lower than that of CCD. More information about CDND should be disseminated by health care professionals. Appropriate guidance will promote the rapid and extensive dissemination of information about the prevention of CDND by media and word-of-mouth peer education.

[The contributing risk factors, prevention and treatment of functional dependence among the oldest-old and elderly subjects].

OBJECTIVE: To compare the risk factors on the functional dependence between the oldest-old and elderly veterans. METHODS: A cross-sectional survey was conducted among veterans ( ≥ 60 years of age) lived in 44 veterans' communities in Beijing. The socio-demographic information and history of non-communicable chronic diseases were collected via face-to-face interviews, and the functional status was assessed by the 20-item version of the Activities of Daily Living Scale. RESULTS: The risk factors associated with increased hazard of the functional dependence in the oldest-old ( ≥ 80 years old) were cognitive impairment, extrapyramidal diseases, cerebral infarction, transient ischemic attack, sleep disorders, hypnotics, osteoarthrosis, hypertension and fall with the odds ratio (OR) of 1.241-2.962 (all P < 0.05). Stroke, depression, cognitive impairment, extrapyramidal diseases, sleep disorders, hypnotics, fall, cardiovascular diseases, osteoarthrosis and hearing loss were the risk factors for that in the elderly subjects (aged 60-79 years). The OR was 1.232-5.790 (all P < 0.05). However, avocational activities such as social activity, physical exercise, photography, reading and games, decreased the risk of functional dependence in both the oldest-old and elderly people. CONCLUSIONS: Neuropsychiatric disorders are the leading causes contributed to the functional dependence among oldest-old and elderly population. Neurodegenerative diseases in the oldest-old, stroke and depression in elderly people should be the priorities in ameliorating disability. Healthy lifestyle and avocational activities could improve the functional status of the oldest-old and elderly population.

Improving the productivity of propionic acid with FBB-immobilized cells of an adapted acid-tolerant Propionibacterium acidipropionici.

Propionic acid is an important short-chain fatty acid with many applications, but its large-scale bioproduction was hindered by the low productivity. An adapted acid-tolerant Propionibacterium acidipropionici CGMCC 1.2230 strain was selected to produce propionic acid with a relatively high productivity (0.29 g/(Lh)) in the free-cell fermentation. Further immobilized-cell fermentation in fibrous-bed bioreactor (FBB) supported high-level repeated batch fermentations with a high productivity of 0.96 g/(Lh). The FBB also presents the potential to increase final propionic acid concentration by using glucose feeding strategy. The propionic acid concentration was increased to 51.2g/L in the fed-batch fermentation with the productivity of 0.71 g/(Lh). By adopting the above strategies, sugarcane bagasse hydrolysate could support the production of propionic acid with high productivity in the repeat-batch and fed-batch fermentations. The present work would pave one road to the accomplishment of large-scale bioproduction of propionic acid from renewable resources.

[A novel recombinant human interferon alpha2b with high antivirus activity by combinatorial mutagenesis].

In order to create a novel recombinant human interferon alpha2b (rh-IFN alpha2b) with higher biological activity, we subjected the rational designed sequence of rh-IFN alpha2b to direct evolution by strategy of the combinatorial mutagenesis. The amino acid residues at multiple sites of 52-53-55, 103-107, and 121-125 were simultaneously mutated. The resulted gene of the mutated rh-IFN a2b was cloned into the pET28a and expressed in E. coli BL21 Condon plus (RIL). The anti-virus activity of the novel interferon alpha2b was 9.3 x 10(7) IU/mg, 93 times higher than the wild type (1 x 10(6) IU/mg). The results showed that the multiple point mutation used in this study could effectively combine the site effects of rh-IFN alpha2b and increase its biological activity.