RplI interacts with 5' UTR of exsA to repress its translation and type III secretion system in Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an important opportunistic pathogen capable of causing variety of infections in humans. The type III secretion system (T3SS) is a critical virulence determinant of P. aeruginosa in the host infections. Expression of the T3SS is regulated by ExsA, a master regulator that activates the expression of all known T3SS genes. Expression of the exsA gene is controlled at both transcriptional and posttranscriptional levels. Here, we screened a P. aeruginosa transposon (Tn5) insertional mutant library and found rplI, a gene coding for the ribosomal large subunit protein L9, to be a repressor for the T3SS gene expression. Combining real-time quantitative PCR (qPCR), western blotting and lacZ fusion assays, we show that RplI controls the expression of exsA at the posttranscriptional level. Further genetic experiments demonstrated that RplI mediated control of the exsA translation involves 5' untranslated region (5' UTR). A ribosome immunoprecipitation assay and qPCR revealed higher amounts of a 24 nt fragment from exsA mRNA being associated with ribosomes in the ΔrplI mutant. An interaction between RplI and exsA mRNA harboring its 24 nt, but not 12 nt, 5' UTR was confirmed by RNA Gel Mobility Shift and Microscale Thermophoresis assays. Overall, this study identifies the ribosomal large subunit protein L9 as a novel T3SS repressor that inhibits ExsA translation in P. aeruginosa.

A New Method for Training CycleGAN to Enhance Images of Cold Seeps in the Qiongdongnan Sea.

Clear underwater images can help researchers detect cold seeps, gas hydrates, and biological resources. However, the quality of these images suffers from nonuniform lighting, a limited range of visibility, and unwanted signals. CycleGAN has been broadly studied in regard to underwater image enhancement, but it is difficult to apply the model for the further detection of Haima cold seeps in the South China Sea because the model can be difficult to train if the dataset used is not appropriate. In this article, we devise a new method of building a dataset using MSRCR and choose the best images based on the widely used UIQM scheme to build the dataset. The experimental results show that a good CycleGAN could be trained with the dataset using the proposed method. The model has good potential for applications in detecting the Haima cold seeps and can be applied to other cold seeps, such as the cold seeps in the North Sea. We conclude that the method used for building the dataset can be applied to train CycleGAN when enhancing images from cold seeps.

Molecular detection of H. pylori antibiotic-resistant genes and molecular docking analysis.

To explore the mutation characteristics of H. pylori resistance-related genes to antibiotics of clarithromycin (CAM), levofloxacin (LVX) and metronidazole, 23SrRNA, gyrA, gyrB, rdxA, and frxA genes were amplified and sequenced, respectively. Molecular docking study was performed to explore molecular interactions between chemotherapeutic agents and target proteins. In the CAM-resistant strains, the mutation rate in site A2143G was 74.2% (n = 23). The interactions in sites of G1949A, C1953T, and G2211T with CAM were weaker after mutation. In the LVX-resistant strains, the mutation rates in 87 (N to K/I) and 91 (D to N/Y/G) of gyrA were 28.6% (n = 16) and 12.5% (n = 7), respectively. We could infer by docking studies that N87 K/I, D91Y/G/N, D99N, and D143E mutations in GyrA protein all had weakened interaction with LVX. The mutation types of RdxA protein consisted of protein truncation caused by premature stop codons (n = 26, 33.3%), frameshift mutations (n = 8, 10.3%), FMN-binding sites (n = 16, 20.5%), and the others (n = 11, 14.1%). Docking analysis showed that some mutations in those four types of RdxA protein could reduce interaction with MNZ, and play a significant role in antibiotic resistance. What's more, we performed natural transformation with some of these mutated DNA fragments to see if they really impact susceptibility to antibiotics. Our study suggested that in addition to the reported mutation sites, H. pylori antibiotic resistance in this region may also be associated with changes in some new sites. Our study provides novel ideas and methods for the identification of H. pylori resistance-related mutations, and also clues and basis for further investigation on specific molecular mechanism.

Identification of cancer stem cell-related biomarkers in intestinal-type and diffuse-type gastric cancer by stemness index and weighted correlation network analysis.

BACKGROUND: Cancer stem cells (CSCs) play an important role in drug resistance, recurrence, and metastasis of tumors. Considering the heterogeneity of tumors, this study aimed to explore the key genes regulating stem cells in intestinal-type and diffuse-type gastric cancer. METHODS: RNA-seq data and related clinical information were downloaded from The Cancer Genome Atlas (TCGA). WGCNA was used to clustered differentially expressed genes with similar expression profiles to form modules. Furtherly, based on the mRNA expression-based stemness index (mRNAsi), significant modules and key genes were identified. Next, the expression of key genes was further verified by the Oncomine database. RESULTS: MRNAsi scores of GC were significantly higher than that of normal tissue. Additionally, mRNAsi scores of intestinal-type GC (IGC) were significantly higher than that of diffuse-type GC (DGC). WGCNA showed that the blue module of IGC and the brown module of DGC were both the most significantly associated with mRNAsi. We screened out 16 and 43 key genes for IGC and DGC and found that these genes were closely related, respectively. Functional analysis showed the relationship between the key genes confirmed in the Oncomine database and the fate of cells. CONCLUSIONS: In this study, 16 and 43 genes related to the characteristics of CSCs were identified in IGC and DGC, respectively. These genes were both associated with cell cycle, which could serve as therapeutic targets for the inhibition of stem cells from both types of GC.

H. pylori slyD, a novel virulence factor, is associated with Wnt pathway protein expression during gastric disease progression.

We have previously reported that the virulence factor HpslyD is related to the occurrence of gastric diseases. However, its mechanism of pathogenesis is still unclear. It is commonly believed that the Wnt/ß-catenin pathway is indispensable for the development of gastric cancer, but it is unclear whether HpslyD and Wnt/ß-catenin interact during the development of gastric diseases. Therefore, we measured the expression of E-cadherin, ß-catenin, TCF4, and CDX2 proteins by IHC in gastric mucosa specimens from patients with different gastric diseases and compared the differences in protein expression to H. pylori-infection status. The results indicated that the expression of these proteins was associated with HpslyD infection. HpslyD subtype infection, rather than common H. pylori infection, may have a greater effect on the expression of Wnt proteins in atrophic gastritis and gastric cancer. Additionally, HpslyD strain infection promoted the expression of Wnt pathway-related proteins with the progression of gastric disease. This study provides insight into the pathogenesis of H. pylori-related gastric diseases and "type-based treatment" for H. pylori infection.

The antibiotic resistance of Helicobacter pylori to five antibiotics and influencing factors in an area of China with a high risk of gastric cancer.

BACKGROUND: H. pylori exhibits antibiotic resistance with regional differences. In this paper, we explored antibiotic resistance of H. pylori to five antibiotics in an area with a high risk of gastric cancer. RESULTS: H. pylori resistance rates to metronidazole, levofloxacin, clarithromycin, amoxicillin, and tetracycline were 78.0, 56.0, 31.0, 9.0, and 15.0%, respectively. Double, triple, quadruple, and quintuple resistance rates were 23, 20, 6, and 4%, respectively. The clarithromycin and multidrug resistance rates were significantly higher in males than females (clarithromycin: 44.4% vs 15.2%, respectively, P = 0.002; multidrug: 75.5% vs 37.2%, respectively; P < 0.001). During the three periods of 1998-1999, 2002-2004 and 2016-2017, the resistance rates to levofloxacin and amoxicillin were increasing (OR: 2.089, 95%CI: 1.142-3.821, P = 0.017; and OR: 5.035, 95%CI: 1.327-19.105, P = 0.018, respectively). The antibiotic resistance rates were unassociated with the host disease state. Metronidazole resistance was lower in the vacAs1m1/m2 group than the vacAs1m1m2 group (65% vs 85.7%, respectively; P = 0.026). As for levofloxacin resistance, it was higher with cagA + than cagA- (60.9% vs 23.1%, respectively; P = 0.020) but lower with slyD+ than slyD- (41.4% vs 68.5%, respectively; P = 0.009). Clarithromycin had a lower resistance rate with iceA++ than iceA-+ (19.7% vs 52.4%, respectively; P = 0.017). For amoxicillin, the iceA++ group had a lower resistance rate than the iceA-- group (1.6% vs 27.8%, respectively; P = 0.009). CONCLUSIONS: The total resistance rates of H. pylori to metronidazole, levofloxacin, clarithromycin, amoxicillin, and tetracycline were high in Zhuanghe. The resistanc rates to levofloxacin and amoxicillin increased over time. Clarithromycin resistance was associated with male and iceA. The resistance of metronidazole was related to vacA. Levofloxacin resistance was concerned with cagA and slyD and amoxicillin resistance was concerned with iceA. While, the antibiotic resistance of H. pylori had nothing to do with the status of gastric disease.

Role of abnormal microRNA expression in Helicobacter pylori associated gastric cancer.

Epidemiological studies have shown that Helicobacter pylori (HP) infection is a risk factor for gastric cancer (GC). HP infection may induce the release of pro-inflammatory mediators, and abnormally increase the level of reactive oxygen species (ROS), nitric oxide (NO), and cytokines in mucosal epithelial cells of the stomach. However, the specific mechanism underlying the pathogenesis of HP-associated GC is still poorly understood. Recent studies have revealed that abnormal microRNA expression may affect the proliferation, differentiation, and apoptosis of mucosal epithelial cells of the stomach to further influence GC occurrence, development, and metastasis. Herein, we summarize the role of abnormal microRNAs in the regulation of HP-associated GC progression. Abnormal microRNA expression in HP-positive GC may be a biomarker for GC diagnosis, occurrence, and development as well as its targeted treatment and prognosis.

ABA receptor PYL9 promotes drought resistance and leaf senescence.

Drought stress is an important environmental factor limiting plant productivity. In this study, we screened drought-resistant transgenic plants from 65 promoter-pyrabactin resistance 1-like (PYL) abscisic acid (ABA) receptor gene combinations and discovered that pRD29A::PYL9 transgenic lines showed dramatically increased drought resistance and drought-induced leaf senescence in both Arabidopsis and rice. Previous studies suggested that ABA promotes senescence by causing ethylene production. However, we found that ABA promotes leaf senescence in an ethylene-independent manner by activating sucrose nonfermenting 1-related protein kinase 2s (SnRK2s), which subsequently phosphorylate ABA-responsive element-binding factors (ABFs) and Related to ABA-Insensitive 3/VP1 (RAV1) transcription factors. The phosphorylated ABFs and RAV1 up-regulate the expression of senescence-associated genes, partly by up-regulating the expression of Oresara 1. The pyl9 and ABA-insensitive 1-1 single mutants, pyl8-1pyl9 double mutant, and snrk2.2/3/6 triple mutant showed reduced ABA-induced leaf senescence relative to the WT, whereas pRD29A::PYL9 transgenic plants showed enhanced ABA-induced leaf senescence. We found that leaf senescence may benefit drought resistance by helping to generate an osmotic potential gradient, which is increased in pRD29A::PYL9 transgenic plants and causes water to preferentially flow to developing tissues. Our results uncover the molecular mechanism of ABA-induced leaf senescence and suggest an important role of PYL9 and leaf senescence in promoting resistance to extreme drought stress.

Resistance mechanisms of Helicobacter pylori and its dual target precise therapy.

Helicobacter pylori drug resistance presents a significant challenge to the successful eradication of this pathogen. To find strategies to improve the eradication efficacy of H. pylori, it is necessary to clarify the resistance mechanisms involved. The mechanisms of H. pylori drug resistance can be investigated from two angles: the pathogen and the host. A comprehensive understanding of the molecular mechanisms of H. pylori resistance based on both pathogen and host would aid the implementation of precise therapy, or ideally "dual target precise therapy" (bacteria and host-specific target therapy). In recent years, with increased understanding of the mechanisms of H. pylori resistance, the focus of eradication has shifted from disease-specific to patient-specific treatment. The implementation of "precision medicine" has also provided a new perspective on the treatment of infectious diseases. In this article, we systematically review current research on H. pylori drug resistance from the perspective of both the pathogen and the host. We also review therapeutic strategies targeted to pathogen and host factors that are aimed at achieving precise treatment of H. pylori.

Serum levels of matrix metalloproteinase 9 and toll-like receptor 4 in acute aortic dissection: a case-control study.

BACKGROUND: Matrix metalloproteinase 9 (MMP9) and Toll-like receptor 4 (TLR4) play important roles in aortic pathophysiology. However, there is lacking research on serum TLR4 levels in acute aortic dissection (AAD) patients, and the performance of serum MMP9 and TLR4 for the diagnosis of AAD is still unknown. This study aimed to evaluate the serum levels of MMP9 and TLR4 in AAD patients, identify their associations with circulating C-reactive protein (CRP) and D-dimer, which are well-known classical biomarkers of AAD, and further explore the potential diagnostic role of MMP9 and TLR4 in AAD. METHODS: Serum levels of MMP9 and TLR4 were measured by enzyme-linked immunosorbent assay (ELISA) in 88 AAD patients and 88 controls. The clinical test related information was collected from patients' electronic medical records. RESULTS: Serum MMP9 and TLR4 levels were significantly higher in AAD patients than those in healthy controls in the general and stratified comparisons. Either serum MMP9 or TLR4 was independently associated with the risk of AAD (all p < 0.001). There was a positive significant association between serum MMP9 and TLR4 (r = 0.518, p < 0.001). Both MMP9 and TLR4 levels were statistically correlated with circulating CRP, but not D-dimer. Based on receiver-operating characteristic (ROC) analysis, the area under the curves (AUCs) of MMP9 and TLR4 alone for the diagnosis of AAD were 0.810 and 0.799 with optimal cut-off points of 379.47 ng/ml and 7.83 ng/ml, respectively. Moreover, a combination of serum MMP9 and TLR4 increased the AUC to 0.89 with a sensitivity of 60.2% and specificity of 94.3%. CONCLUSIONS: Serum MMP9 and TLR4 could be potential biomarkers for identifying AAD, while the combined diagnostic value was higher in safely ruling out AAD.

A Serological Biopsy Using Five Stomach-Specific Circulating Biomarkers for Gastric Cancer Risk Assessment: A Multi-Phase Study.

OBJECTIVES: We aimed to assess a serological biopsy using five stomach-specific circulating biomarkers-pepsinogen I (PGI), PGII, PGI/II ratio, anti-Helicobacter pylori (H. pylori) antibody, and gastrin-17 (G-17)-for identifying high-risk individuals and predicting risk of developing gastric cancer (GC). METHODS: Among 12,112 participants with prospective follow-up from an ongoing population-based screening program using both serology and gastroscopy in China, we conducted a multi-phase study involving a cross-sectional analysis, a follow-up analysis, and an integrative risk prediction modeling analysis. RESULTS: In the cross-sectional analysis, the five biomarkers (especially PGII, the PGI/II ratio, and H. pylori sero-positivity) were associated with the presence of precancerous gastric lesions or GC at enrollment. In the follow-up analysis, low PGI levels and PGI/II ratios were associated with higher risk of developing GC, and both low (<0.5 pmol/l) and high (>4.7 pmol/l) G-17 levels were associated with higher risk of developing GC, suggesting a J-shaped association. In the risk prediction modeling analysis, the five biomarkers combined yielded a C statistic of 0.803 (95% confidence interval (CI)=0.789-0.816) and improved prediction beyond traditional risk factors (C statistic from 0.580 to 0.811, P<0.001) for identifying precancerous lesions at enrollment, and higher serological biopsy scores based on the five biomarkers at enrollment were associated with higher risk of developing GC during follow-up (P for trend <0.001). CONCLUSIONS: A serological biopsy composed of the five stomach-specific circulating biomarkers could be used to identify high-risk individuals for further diagnostic gastroscopy, and to stratify individuals' risk of developing GC and thus to guide targeted screening and precision prevention.

Polymorphic rs9471643 and rs6458238 upregulate PGC transcription and protein expression in overdominant or dominant models.

The pepsinogen C (PGC) gene encodes a major differentiation biomarker for gastric mucosa and has two single nucleotide polymorphisms, rs9471643 G>C and rs6458238 G>A, within its 5' upstream region that are involved in gastric carcinogenesis. However, in what genetic models the two polymorphisms modulate disease risk and how they relate to gastric carcinogenesis needs further study. We fitted the most appropriate genetic models to the PGC polymorphisms and validated their robustness; then with knowledge of the genetic model, we investigated the influence of functional variant alleles or genotypes on gene expression in vitro and in vivo. We confirmed that rs9471643 CG genotype was stably associated with reduced gastric cancer risk in complete overdominant model. This favorable CG genotype was also associated with reduced atrophic gastritis risk in subjects carrying rs6458238 AG/AA genotype. The G>C transition at rs9471643 enhanced promoter activity and transcription factor binding ability, and the CG genotype was consistently associated with elevated levels of PGC mRNA, in situ protein and serum protein in complete overdominant model based-analyses. Additionally, rs6458238 AG/AA genotype was associated with reduced atrophic gastritis risk in dominant model. Its favorable A allele was related to higher promoter activity and lower transcription factor binding ability, and the AG/AA genotype showed association with elevated levels of serum PGC protein in dominant model based-analyses. Our results suggest that rs9471643 CG and rs6458238 AG/AA genotypes have important roles in up-regulating PGC expression, which may partially explain why individuals with these favorable genotypes have decreased risks of getting gastric cancer.

RDM4 modulates cold stress resistance in Arabidopsis partially through the CBF-mediated pathway.

The C-REPEAT-BINDING FACTOR (CBF) pathway has important roles in plant responses to cold stress. How the CBF genes themselves are activated after cold acclimation remains poorly understood. In this study, we characterized cold tolerance of null mutant of RNA-DIRECTED DNA METHYLATION 4 (RDM4), which encodes a protein that associates with RNA polymerases Pol V and Pol II, and is required for RNA-directed DNA methylation (RdDM) in Arabidopsis. The results showed that dysfunction of RDM4 reduced cold tolerance, as evidenced by decreased survival and increased electrolyte leakage. Mutation of RDM4 resulted in extensive transcriptomic reprogramming. CBFs and CBF regulon genes were down-regulated in rdm4 but not nrpe1 (the largest subunit of PolV) mutants, suggesting that the role of RDM4 in cold stress responses is independent of the RdDM pathway. Overexpression of RDM4 constitutively increased the expression of CBFs and regulon genes and decreased cold-induced membrane injury. A great proportion of genes affected by rdm4 overlapped with those affected by CBFs. Chromatin immunoprecipitation results suggested that RDM4 is important for Pol II occupancy at the promoters of CBF2 and CBF3. We present evidence of a considerable role for RDM4 in regulating gene expression at low temperature, including the CBF pathway in Arabidopsis.

Serum VacA antibody is associated with risks of peptic ulcer and gastric cancer: A meta-analysis.

BACKGROUND: Increasing studies have investigated the relationship between the status of H. pylori vacA antibody and risks of peptic ulcer disease (PUD) and gastric cancer (GC). However, the results were controversial. The aim of this meta-analysis is to clarify whether serum vacA antibody is associated with risks of PUD and GC. METHODS: Databases including PubMed, Embase, Web of knowledge, Wanfang, Chinese National Knowledge Infrastructure (CNKI), OVID, Karger and Scopus were systematically searched for potentially eligible literature. Odds ratios (OR) and their 95% confidence interval (CI) were adopted to assess the strength of association. RESULTS: Serum VacA antibody was associated with increased risk of PUD compared with gastritis/functional dyspepsia (FD) (OR = 1.96, 95%CI = 1.56-2.46, P < 0.001). Serum VacA antibody was significantly associated with increased risk of gastric ulcer (GU) and duodenal ulcer (DU) compared with gastritis/FD (GU: OR = 1.64, 95%CI = 1.02-2.62, P = 0.042; DU: OR = 2.06, 95%CI = 1.50-2.84, P < 0.001, respectively). Significant increased risk of GC was found in serum VacA antibody positive subjects compared with serum VacA antibody negative individuals (OR = 2.78, 95%CI = 1.98-3.89, P < 0.001). There was no significant publication bias in all of the comparisons. CONCLUSIONS: Serum VacA antibody was significantly associated with increased risks of peptic ulcer disease, gastric ulcer and duodenal ulcer compared with gastritis and functional dyspepsia controls. Significant association was also found between serum VacA antibody and gastric cancer risk. Serum VacA antibody might be a potential biomarker for the prediction of risks of PUD and GC.

Temporal changes in serum biomarkers and risk for progression of gastric precancerous lesions: a longitudinal study.

Effectively managing precancerous lesions is crucial to reducing the gastric cancer (GC) burden. We evaluated associations of temporal changes in multiple serological markers (pepsinogen I [PGI], PGII, PGI/II ratio, gastrin-17 and anti-Helicobacter pylori IgG) with risk for progression of gastric precancerous lesions. From 1997 to 2011, repeated esophagogastroduodenoscopies with gastric mucosal biopsies and blood sample collections were conducted on 2,039 participants (5,070 person-visits) in the Zhuanghe Gastric Diseases Screening Program, Liaoning, China. Serum biomarkers were measured using ELISA, and gastric biopsies were evaluated using standardized histologic criteria. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using generalized estimating equations for correlated binary outcomes. The ORs for progression of gastric conditions comparing those whose serum PGI, PGII, and anti-H. pylori IgG levels increased ≥ 50% relative to those whose decreased ≥ 50% were, respectively 1.67 (CI, 1.22-2.28), 1.80 (CI, 1.40-2.33) and 1.93 (CI, 1.48-2.52). The OR for those whose PGI/II ratio decreased ≥ 50% relative to those whose increased ≥ 50% was 1.40 (CI, 1.08-1.81), and for those whose PGII and anti-H. pylori IgG levels both increased ≥ 50% relative to those whose levels both decreased ≥ 50% the OR was 3.18 (CI, 2.05-4.93). Changes in gastrin-17 were not statistically significantly associated with progression. These findings suggest that temporal changes in serum PGI, PGII, PGI/II ratio, and anti-H. pylori IgG levels (especially PGII and anti-H. pylori IgG combined) may be useful for assessing and managing risk for progression of gastric precancerous lesions.

Helicobacter pylori Infection Status Correlates with Serum Parameter Levels Responding to Multi-organ Functions.

BACKGROUND: Epidemiological studies have demonstrated the relationship between Helicobacter pylori infection and gastric and extra-gastric diseases. Therefore, H. pylori infection might be a "systemic" disease. AIM: To investigate the relationship between H. pylori infection status and serum parameter levels responding to multi-organ functions. METHODS: A total of 2,044 subjects were selected, including 1,249 males and 795 females with ages ranging from 16 to 86 years. Relevant parameters including blood lipids, complete blood count, tumor markers, indexes of stomach, kidney, liver, thyroid, and immune system function, H.pylori IgG antibody levels, and (14)C-UBT were collected. RESULTS: Serum pepsinogen (PG)I, PGII, and gastrin (G)17 levels were decreased in chronic long-term, past, and acute short-term infection patients compared with uninfected controls. However, the serum PGI/II ratio increased gradually. Serum white blood cell levels gradually decreased in past, chronic long-term, and acute short-term infection patients compared with uninfected controls. The same trend was also observed for CD4(+) T cell levels. In addition, LDL levels were higher in chronic long-term infection, HDL levels were lower in past infection, and ALP and CEA levels were higher in acute short-term infection compared with the uninfected group. CONCLUSIONS: Helicobacter pylori infection correlated with increased PGI, PGII, G17, WBC, and CD4(+) T cell levels, and decreased PGI/II ratio. In chronic long-term or past infection, H. pylori infection was associated with higher LDL or lower HDL levels. In acute short-term infection, H. pylori infection correlated with higher ALP and CEA levels. H. pylori infection correlated with serum parameter levels responding to multi-organ functions.

Characterization, isolation, and culture of mouse and human spermatogonial stem cells.

Spermatogenesis is a special process by which spermatogonial stem cells (SSCs) divide and differentiate to male gametes called mature spermatozoa. SSCs are the unique cells because they are adult stem cells that transmit genetic information to subsequent generations. Accumulating evidence has demonstrated that SSCs can be reprogrammed to acquire pluripotency to become embryonic stem-like cells that differentiate into all cell lineages of the three germ layers, highlighting potential important applications of SSCs for regenerative medicine. Recent studies from peers and us have made great achievements on the characterization, isolation, and culture of mouse and human SSCs, which could lead to better understanding the biology of SSCs and the applications of SSCs in both reproductive and regenerative medicine. In this review, we first compared the cell identity and biochemical phenotypes between mouse SSCs and human SSCs. Notably, the cell types of mouse and human SSCs are distinct, and human SSCs share some but not all phenotypes with mouse SSCs. The approaches for isolating SSCs as well as short- and long-term culture of mouse SSCs and short-period culture of human SSCs were also discussed. We further addressed the new advances on the self-renewal of SSCs with an aim to establish the long-term culture of human SSCs which has not yet been achieved.

Generation of male differentiated germ cells from various types of stem cells.

Infertility is a major and largely incurable disease caused by disruption and loss of germ cells. It affects 10-15% of couples, and male factor accounts for half of the cases. To obtain human male germ cells 'especially functional spermatids' is essential for treating male infertility. Currently, much progress has been made on generating male germ cells, including spermatogonia, spermatocytes, and spermatids, from various types of stem cells. These germ cells can also be used in investigation of the pathology of male infertility. In this review, we focused on advances on obtaining male differentiated germ cells from different kinds of stem cells, with an emphasis on the embryonic stem (ES) cells, the induced pluripotent stem (iPS) cells, and spermatogonial stem cells (SSCs). We illustrated the generation of male differentiated germ cells from ES cells, iPS cells and SSCs, and we summarized the phenotype for these stem cells, spermatocytes and spermatids. Moreover, we address the differentiation potentials of ES cells, iPS cells and SSCs. We also highlight the advantages, disadvantages and concerns on derivation of the differentiated male germ cells from several types of stem cells. The ability of generating mature and functional male gametes from stem cells could enable us to understand the precise etiology of male infertility and offer an invaluable source of autologous male gametes for treating male infertility of azoospermia patients.

Serum anti-Helicobacter pylori immunoglobulin G titer correlates with grade of histological gastritis, mucosal bacterial density, and levels of serum biomarkers.

OBJECTIVE. Clinical implications of serum anti-Helicobacter pylori immunoglobulin G (IgG) titer were unclear. This study investigated the associations of serum anti-H. pylori IgG titer with grade of histological gastritis, mucosal bacterial density and levels of serum biomarkers, including pepsinogen (PG) I, PGII, PGI/II ratio and gastrin-17. MATERIAL AND METHODS. Study participants were from a screening program in northern China. Serum anti-H. pylori IgG measurements were available for 5922 patients with superficial gastritis. Serum anti-H. pylori IgG titer and serum biomarkers were measured using ELISA, and gastric biopsies were evaluated using standardized criteria. RESULTS. In patients with mild, moderate or severe superficial gastritis, the mean serum anti-H. pylori IgG titers were 17.3, 33.4 and 54.4 EIU (p for trend < 0.0001), respectively. As mucosal H. pylori density score increased from 0 to 3, the mean serum anti-H. pylori IgG titers also increased from 24.7 to 44.8 EIU (p for trend < 0.0001). Serum anti-H. pylori IgG titer was associated positively with serum PGI, PGII and gastrin-17 concentrations and negatively with PGI/II ratio, and the association was the strongest for PGII. The mean PGII concentration of the patients in the highest quartile of IgG titer was twice the mean concentration of the patients in the lowest quartile (17.2 vs. 8.6 EIU, p < 0.0001). CONCLUSIONS. Our results suggest that serum anti-H. pylori IgG titer was associated positively with grade of histological gastritis, mucosal bacterial density and concentrations of serum PGI, PGII and gastrin-17, and negatively with PGI/II ratio.

A comprehensive evaluation of fasting serum gastrin-17 as a predictor of diseased stomach in Chinese population.

BACKGROUND AND AIM: Fasting serum gastrin-17 (FsG17) is considered as a noninvasive biomarker reflecting the structure and functional status of gastric mucosa, but its clinical utility remains unclear. This study aimed to evaluate FsG17 comprehensively: establish the ranges and cut-off points of FsG17 levels in different gastric diseases, identify their influencing factors, and investigate the accuracy of FsG17 for identifying diseased stomach. METHODS: The study included 4064 participants from Northern China between 2008 and 2013. FsG17 and serum Helicobacter pylori IgG antibody levels were measured by enzyme-linked immunosorbent assay. Diagnostic accuracy was assessed by receiver operator characteristic curves. Multivariate logistic regression analysis was performed to determine the best predictors of gastric histopathological conditions. RESULTS: Median FsG17 levels in healthy, non-atrophic, atrophic, and cancerous stomachs were 1.8, 4.0, 3.8, and 6.1 pmol/l, respectively. Age, smoking status, alcohol consumption, H. pylori infection, and predominant lesion site were factors that affected FsG17 levels. The optimal cut-off values for FsG17 were 3.0 pmol/l (sensitivity of 59.3% and specificity of 67.3%) for discriminating between healthy stomach and diseased stomach and 10.7 pmol/l (sensitivity of 37% and specificity of 83.7%) for discriminating between cancerous stomach and cancer-free stomach; the screening accuracy was higher (sensitivity of 50.0% and specificity of 83.0%) for gastric cancer in the corpus. Multivariate analysis showed that FsG17, gender, age, and H. pylori infection were independent predictors of cancerous stomach. CONCLUSION: With the progression from health stomach to malignancy, FsG17 levels significantly increased and were influenced by other factors. FsG17 combined with age, gender, and H. pylori infection could distinguish between cancerous stomach and cancer-free stomach. The results will enhance our understanding of the potential clinical utility of FsG17.