Interaction Between Hypoxia-Inducible Factor 1-alpha Gene Polymorphism and Helicobacter pylori Infection on Gastric Cancer in a Chinese Tibetan Population.

To investigate the impact of four single nucleotide polymorphisms (SNPs) of the HIF1α gene and its interaction with Helicobacter pylori (H. pylori) infection on susceptibility to gastric cancer (GC).Logistic regression was used to test the relationship between four SNPs of HIF1α gene and the susceptibility of GC. A generalized multifactor dimensionality reduction (GMDR) model was used to assess the HIF1α gene-H. pylori infection interaction.Logistic regression analysis indicated that both the rs11549465-CT genotype and the T allele were associated with an increased risk of GC, adjusted OR (95% CI) were 1.63 (1.09-2.20) (CT vs. CC) and 1.70 (1.13-2.36) (T vs. C), respectively. We also found that both the rs11549467-A allele and rs11549467-GA genotype were associated with an increased risk of GC, and adjusted OR (95% CI) were 2.21 (1.61-2.86) (GA vs. GG), 2.13 (1.65-2.65) (A vs. G), respectively. However, no statistically significant impact of rs2057482 or rs1957757 on risk of GC was found. The GMDR model indicated a statistically significant two-dimensional model combination (including rs11549467 and H. pylori infection). The selected model had testing balanced accuracy of 0.60 and the best cross-validation consistencies of 10/10 (p = 0.0107). Compared with H. pylori infection negative participants with rs11549467-GG genotype, H. pylori positive participants with the rs11549467-GA genotype had the highest GC risk, the OR (95% CI) was 3.04 (1.98-4.12).The rs11549467-A allele and rs11549467-GA genotype was associated with increased GC risk. Additionally, the gene-environment interaction between HIF-1α-rs11549467 and H. pylori infection was also correlated with an increased risk of GC.

Human immunodeficiency virus-associated dementia complex with positive 14-3-3 protein in cerebrospinal fluid: A case report.

BACKGROUND: Human immunodeficiency virus (HIV)-associated dementia (HAD) is a subcortical form of dementia characterized by memory deficits and psychomotor slowing. However, HAD often presents with symptoms similar to those of Creutzfeldt-Jakob disease (CJD), particularly in patients with acquired immune deficiency syndrome (AIDS). CASE SUMMARY: We report the case of a 54-year-old male who exhibited cognitive dysfunction and secondary behavioral changes following HIV infection and suspected prion exposure. The patient was diagnosed with HIV during hospitalization and his cerebrospinal fluid tested positive for 14-3-3 proteins. His electroencephalogram showed a borderline-abnormal periodic triphasic wave pattern. Contrast-enhanced magnetic resonance imaging revealed moderate encephalatrophy and demyelination. Initially, symptomatic treatment and administration of amantadine were pursued for presumed CJD, but the patient's condition continued to deteriorate. By contrast, the patient's condition improved following anti-HIV therapy. This individual is also the only patient with this prognosis to have survived over 4 years. Thus, the diagnosis was revised to HAD. CONCLUSION: In the diagnostic process of rapidly progressive dementia, it is crucial to rule out as many potential causes as possible and to consider an autopsy to diminish diagnostic uncertainty. The 14-3-3 protein should not be regarded as the definitive marker for CJD. Comprehensive laboratory screening for infectious diseases is essential to enhance diagnostic precision, especially in AIDS patients with potential CJD. Ultimately, a trial of diagnostic treatment may be considered when additional testing is not feasible.

Novel noninvasive indices for the assessment of liver fibrosis in primary biliary cholangitis.

The present study aimed to investigate the accuracy of new noninvasive markers in predicting liver fibrosis among individuals with primary biliary cholangitis (PBC). This retrospective analysis included subjects with PBC who had liver biopsies. Scheuer's classification was used to determine the fibrosis stage. The bilirubin to albumin (Alb) ratio (BAR), fibrosis index based on the four factors (FIB-4), γ-glutamyl transpeptidase to platelet (PLT) ratio (GPR), red cell distribution width to PLT ratio (RPR), aspartate aminotransferase (AST) to alanine aminotransferase ratio (AAR), AST to PLT ratio index (APRI) and total bilirubin to PLT ratio (TPR) were calculated based on the laboratory parameters. A novel index called BARP was conceived as BAR x RPR. A total of 78 individuals with PBC were included in the study, 84.6% of whom had significant fibrosis, 30.8% had advanced fibrosis and 15.4% had cirrhosis. In the multivariate analysis, Alb was determined to be an independent predictor of advanced fibrosis (odds ratio=0.823, P=0.034). The area under the receiver operating characteristic curves (AUROCs) of the BAR, GPR, TPR and BARP were statistically significant in predicting severe fibrosis (P<0.05) and were 0.747, 0.684, 0.693 and 0.696, respectively. In assessing advanced fibrosis, the AUROCs for the AAR, APRI, BAR, FIB-4, RPR, TPR and BARP were 0.726, 0.650, 0.742, 0.716, 0.670, 0.735 and 0.750, respectively. The AUROCs for the APRI, BAR, FIB-4, RPR, TPR and BARP for cirrhosis prediction were 0.776, 0.753, 0.821, 0.819, 0.808 and 0.832, respectively. By comparing the AUROCs, it was demonstrated that the diagnostic capabilities of the BARP (P=0.021) and TPR (P=0.044) were superior to those of the APRI in predicting advanced fibrosis. In conclusion, the BAR, BARP and TPR were of predictive value for the grade of liver fibrosis in PBC and Alb had a diagnostic value in identifying early fibrosis. The aforementioned noninvasive indices may be used for predicting histologic stages of PBC.

Transporter mining and metabolic engineering of Escherichia coli for high-level D-allulose production from D-fructose by thermo-swing fermentation.

D-Allulose is an ultra-low-calorie sweetener with broad market prospects in the fields of food, beverage, health care, and medicine. The fermentative synthesis of D-allulose is still under development and considered as an ideal route to replace enzymatic approaches for large-scale production of D-allulose in the future. Generally, D-allulose is synthesized from D-fructose through Izumoring epimerization. This biological reaction is reversible, and a high temperature is beneficial to the conversion of D-fructose. Mild cell growth conditions seriously limit the efficiency of producing D-allulose through fermentation. FryABC permease was identified to be responsible for the transport of D-allulose in Escherichia coli by comparative transcriptomic analysis. A cell factory was then developed by expression of ptsG-F, dpe, and deletion of fryA, fruA, manXYZ, mak, and galE. The results show that the newly engineered E. coli was able to produce 32.33 ± 1.33 g L-1 of D-allulose through a unique thermo-swing fermentation process, with a yield of 0.94 ± 0.01 g g-1 on D-fructose.

Mameliella sediminis sp. nov., a novel polyhydroxyalkanoate-accumulating bacterium.

A Gram-stain-negative, strictly aerobic, non-motile, rod-shaped bacterium, capable of producing poly-ß-hydroxyalkanoate, designated DP3N28-2T, was isolated from the sediment collected from Daya Bay, Guangdong, PR China. Optimal growth occurred at 37-40 °C, pH 6.0 and in the presence of 4 % NaCl. The 16S rRNA gene sequences analysis revealed that DP3N28-2T showed highest similarities with Mameliella alba DSM 23384T (98.3 %), Antarctobacter jejuensis 13-2-B6T (97.2 %), Antarctobacter heliothermus El-219T (96.8 %), Maliponia aquimaris MM-10T (96.7 %), Ponticoccus litoralis CL-GR66T (96.4 %) and Aquicoccus porphyridii L1 8-17T (96.1 %). The predominant fatty acids (>10 %) were summed feature 8 (C18 : 1ω6c and/or C18 : 1ω7c; 72.1 %) and C16 : 0 (11.0 %). The polar lipids contain phosphatidylethanolamine, phosphatidylmonomethylethanolamine, phosphatidylglycerol, one aminophosphlipid, one phospholipid and three unidentified lipids. The respiratory quinone was Q-10. The DNA G+C content was 63.0 mol% (data from the genome sequence). The estimated genome size was 5.12 Mb. The average nucleotide identity values between the DP3N28-2T genome and the genome of M. alba was 81.1 %, while the digital DNA-DNA hybridization value was 23.4 %. The phenotypic, genotypic and chemotaxonomic differences between DP3N28-2T and its phylogenetic relatives indicates that DP3N28-2T should be regarded as representing a novel species of the genus Mameliella, for which the name Mameliella sediminis sp. nov. is proposed. The type strain is DP3N28-2T (=MCCC 1K06218T=KCTC 82804T).

Sensitive and selective nitrite assay based on fluorescent gold nanoclusters and Fe2+/Fe3+ redox reaction.

In recent years, gold nanoclusters (AuNCs) have received considerable attention as optical transducers in chemo/biosensors. Herein, a facile and efficient assay for NO2- has been successfully developed based on the fluorescence quenching of AuNCs co-modified by bovine serum albumin and 3-mercaptopropionic acid (BSA/MPA-AuNCs). In the presence of NO2- under acidic conditions, Fe2+ can be readily oxidized and transformed to Fe3+, which can significantly suppress the fluorescence of BSA/MPA-AuNCs via non-radiative electron-transfer mechanism. The linear range and detection limit for this system were found to be 5-30 µM (r = 0.9975) and 0.7 µM, respectively. Other common anions and cations showed only very minor interference with the NO2- detection. Furthermore, the effectiveness of the proposed sensing strategy was validated by the demonstration of good performance in the determination of the amount of NO2- in ham samples, rendering it a powerful tool for the assessment of food security and water quality.

Lactoferrin ameliorates aging-suppressed osteogenesis via IGF1 signaling.

Lactoferrin (LF) is an iron-binding glycoprotein that plays an important role in promoting bone formation and inhibiting bone resorption; however, its effects on senile osteoporosis remain unknown. This study aimed to investigate the effects and mechanism of LF intervention using a senile osteoporosis model (SAMP6 mice) and senescent osteoblasts. Micro-CT and hematoxylin and eosin staining demonstrated that the intragastric administration (2 g/kg/day) of LF could improve the bone mass and microstructure of SAMP6 mice. Furthermore, LF treatment improved bone metabolism and increased insulin-like growth factor 1 (Igf1) mRNA expression and activated phosphorylation status of AKT. Using osteoblasts passaged for ten generations as an in vitro senescence model, various markers associated with osteoblast formation and differentiation, as well as related indices of oxidative stress were analyzed. Our results revealed that after multiple generations, osteoblasts entered senescence, in conjunction with increased oxidative stress damage, reduced bone metabolism and enhanced expression of aging-related markers. While inhibiting oxidative stress, LF improved osteoblast proliferation by promoting the expression of osteogenesis markers, including alkaline phosphatase (ALP) activity, Igf1, bone gla protein (Bglap) and osteoprotegerin/receptor activator of nuclear factor-kB ligand (Opg/Rankl) mRNA and delayed senescence by decreasing the level of p16 and p21 expression. RNAI-mediated downregulation of IGF1 attenuated the effect of LF on osteogenesis. Therefore, the findings of the present study indicate that LF may promote osteogenesis via IGF1 signaling, thereby preventing senile osteoporosis.

Synthesis, Anti-inflammatory Activities and Mechanisms of 3,5- dihydroxycinnamic Acid Derivatives.

BACKGROUND: 3,4-dihydroxycinnamic acid and its derivatives exhibit numerous biologic activities. Such activities have not previously been reported for 3,5-dihydroxycinnamic acid derivatives. In this study, ten derivatives of 3,5- dihydroxycinnamic acid were synthesized and their anti-inflammatory activities were tested in 12-O-tetradecanoylphorbol 13-acetate-induced mouse ear edema. Molecular biological studies have shed lights on their anti-inflammatory mechanism. METHODS: Anti-inflammatory activities of ten new synthesized derivatives of 3,5-dihydroxycinnamic acid were tested in 12-O-tetradecanoylphorbol 13-acetate-induced mouse ear edema, and their anti-inflammatory mechanism was studied by ELISA, real-time RT-PCR, MPO assay and AA-induced mouse ear edema. RESULTS: Compound 7 showed a pronounced anti-inflammatory effect and the inhibition rate was 65.6% at a dose of 1.6mg/ear. This compound acted by reducing mRNA and protein synthesis of tumor necrosis factor-α, interleukins 1ß and 6, and also by decreasing the levels of activated neutrophil infiltrates. Furthermore, compound 7 significantly suppressed arachidonic acid-induced edema as well. Cell-based assays showed that compound 7 inhibited the production of cyclooxygenase- 2-catalyzed prostaglandin E2 from lipopolysaccharide-treated RAW 264.7 cells, and also inhibited 5-lipoxygenase production from A23187-treated RBL-1 cells, and consequently reduced leukotriene B4 production. CONCLUSION: This investigation revealed that some of the derivatives of 3,5-dihydroxycinnamic acid exhibit a more pronounced anti-inflammatory effect than 3,4-dihydroxycinnamic acid. Therefore, 3,5-dihydroxycinnamic acid derivatives, especially compound 7, represent potential value for antiinflammatory drug development.