Characterization of cytotoxic Citrobacter braakii isolated from human stomach.

Citrobacter braakii (C. braakii) is an anaerobic, gram-negative bacterium that has been isolated from the environment, food, and humans. Infection by C. braakii has been associated with acute mucosal inflammation in the intestine, respiratory tract, and urinary tract. However, the pathogenesis of C. braakii in the gastric mucosa has not yet been clarified. In this study, the bacterium was detected in 35.5% (61/172) of patients with chronic gastritis (CG) and was closely associated with the severity of mucosal inflammation. Citrobacter braakii P1 isolated from a patient with CG exhibited urease activity and acid resistance. It contained multiple secretion systems, including a complete type I secretion system (T1SS), T5aSS and T6SS. We then predicted the potential pilus-related adhesins. Citrobacter braakii P1 diffusely adhered to AGS cells and significantly increased lactate dehydrogenase (LDH) release; the adhesion rate and LDH release were much lower in HEp-2 cells. Strain P1 also induced markedly increased mRNA and protein expression of IL-8 and TNF-α in AGS cells, and the fold increase was much higher than that in HEp-2 cells. Our results demonstrate proinflammatory and cytotoxic role of C. braakii in gastric epithelial cells, indicating the bacterium is potentially involved in inducing gastric mucosa inflammation.

Evaluation of polygenic risk score for risk prediction of gastric cancer.

Genetic variations are associated with individual susceptibility to gastric cancer. Recently, polygenic risk score (PRS) models have been established based on genetic variants to predict the risk of gastric cancer. To assess the accuracy of current PRS models in the risk prediction, a systematic review was conducted. A total of eight eligible studies consisted of 544842 participants were included for evaluation of the performance of PRS models. The overall accuracy was moderate with Area under the curve values ranging from 0.5600 to 0.7823. Incorporation of epidemiological factors or Helicobacter pylori (H. pylori) status increased the accuracy for risk prediction, while selection of single nucleotide polymorphism (SNP) and number of SNPs appeared to have little impact on the model performance. To further improve the accuracy of PRS models for risk prediction of gastric cancer, we summarized the association between gastric cancer risk and H. pylori genomic variations, cancer associated bacteria members in the gastric microbiome, discussed the potentials for performance improvement of PRS models with these microbial factors. Future studies on comprehensive PRS models established with human SNPs, epidemiological factors and microbial factors are indicated.

Microbial dysbiosis in oral squamous cell carcinoma: A systematic review and meta-analysis.

Objective: The aim of this study was to summarize previously published data and assess the alterations in the composition of the oral microbiome in OSCC using a systematic review and meta-analysis. Design: Electronic databases were systematically searched for studies on the oral microbiome in OSCC published before December 2021. Qualitative assessments of compositional variations at the phylum level were performed. The meta-analysis on abundance changes of bacteria genera was performed via a random-effects model. Results: A total of 18 studies involving 1056 participants were included. They consisted of two categories of studies: 1) case-control studies (n = 9); 2) nine studies that compared the oral microbiome between cancerous tissues and paired paracancerous tissues. At the phylum level, enrichment of Fusobacteria but depletion in Actinobacteria and Firmicutes in the oral microbiome was demonstrated in both categories of studies. At the genus level, Fusobacterium showed an increased abundance in OSCC patients (SMD = 0.65, 95% CI: 0.43-0.87, Z = 5.809, P = 0.000) and in cancerous tissues (SMD = 0.54, 95% CI: 0.36-0.72, Z = 5.785, P = 0.000). The abundance of Streptococcus was decreased in OSCC (SMD = -0.46, 95% CI: -0.88-0.04, Z = -2.146, P = 0.032) and in cancerous tissues (SMD = -0.45, 95% CI: -0.78-0.13, Z = -2.726, P = 0.006). Conclusions: Disturbances in the interactions between enriched Fusobacterium and depleted Streptococcus may participate in or prompt the occurrence and development of OSCC and could be potential biomarkers for detection of OSCC.

Prediction of gastric cancer risk by a polygenic risk score of Helicobacter pylori.

BACKGROUND: Genetic variants of Helicobacter pylori (H. pylori) are involved in gastric cancer occurrence. Single nucleotide polymorphisms (SNPs) of H. pylori that are associated with gastric cancer have been reported. The combined effect of H. pylori SNPs on the risk of gastric cancer remains unclear. AIM: To assess the performance of a polygenic risk score (PRS) based on H. pylori SNPs in predicting the risk of gastric cancer. METHODS: A total of 15 gastric cancer-associated H. pylori SNPs were selected. The associations between these SNPs and gastric cancer were further validated in 1022 global strains with publicly available genome sequences. The PRS model was established based on the validated SNPs. The performance of the PRS for predicting the risk of gastric cancer was assessed in global strains using quintiles and random forest (RF) methods. The variation in the performance of the PRS among different populations of H. pylori was further examined. RESULTS: Analyses of the association between selected SNPs and gastric cancer in the global dataset revealed that the risk allele frequencies of six SNPs were significantly higher in gastric cancer cases than non-gastric cancer cases. The PRS model constructed subsequently with these validated SNPs produced significantly higher scores in gastric cancer. The odds ratio (OR) value for gastric cancer gradually increased from the first to the fifth quintile of PRS, with the fifth quintile having an OR value as high as 9.76 (95% confidence interval: 5.84-16.29). The results of RF analyses indicated that the area under the curve (AUC) value for classifying gastric cancer and non-gastric cancer was 0.75, suggesting that the PRS based on H. pylori SNPs was capable of predicting the risk of gastric cancer. Assessing the performance of the PRS among different H. pylori populations demonstrated that it had good predictive power for cancer risk for hpEurope strains, with an AUC value of 0.78. CONCLUSION: The PRS model based on H. pylori SNPs had a good performance for assessment of gastric cancer risk. It would be useful in the prediction of final consequences of the H. pylori infection and beneficial for the management of the infection in clinical settings.

Cosmetic-Derived Mannosylerythritol Lipid-B-Phospholipid Nanoliposome: An Acid-Stabilized Carrier for Efficient Gastromucosal Delivery of Amoxicillin for In Vivo Treatment of Helicobacter pylori.

Helicobacter pylori infection is a leading cause of gastritis and peptic ulcer. Current treatments for H. pylori are limited by the increase in antibiotic-resistant strains and low drug delivery to the infection site, indicating the need for effective delivery systems of antibiotics. Although liposomes are the most successful drug delivery carriers that have already been applied commercially, their acidic stability still stands as a problem. Herein, we developed a novel nanoliposome using cosmetic raw materials of mannosylerythritol lipid-B (MEL-B), soy bean lecithin, and cholesterol, namely, LipoSC-MELB. LipoSC-MELB exhibited enhanced stability under the simulated gastric-acid condition, owing to its strong intermolecular hydrogen-bond interactions caused by the incorporation of MEL-B. Moreover, amoxicillin-loaded LipoSC-MELB (LipoSC-MELB/AMX) had a particle size of approximately 100 nm and exhibited sustained drug release under varying pH conditions (pH 3-7). Besides, LipoSC-MELB/AMX exhibited significantly higher anti-H. pylori and anti-H. pylori biofilm activity as compared with free AMX. Furthermore, LipoSC-MELB was able to carry AMX across the barriers of gastric mucus and H. pylori biofilms. Remarkably, in vivo assays indicated that LipoSC-MELB/AMX was effective in treating H. pylori infection and its associated gastritis and gastric ulcers. Overall, the findings of this study showed that LipoSC-MELB was effective for gastromucosal delivery of amoxicillin to improve its bioavailability for the treatment of H. pylori infection.

Frameshift and wild-type proteins are often highly similar because the genetic code and genomes were optimized for frameshift tolerance.

Frameshift mutations have been considered of significant importance for the molecular evolution of proteins and their coding genes, while frameshift protein sequences encoded in the alternative reading frames of coding genes have been considered to be meaningless. However, functional frameshifts have been found widely existing. It was puzzling how a frameshift protein kept its structure and functionality while substantial changes occurred in its primary amino-acid sequence. This study shows that the similarities among frameshifts and wild types are higher than random similarities and are determined at different levels. Frameshift substitutions are more conservative than random substitutions in the standard genetic code (SGC). The frameshift substitutions score of SGC ranks in the top 2.0-3.5% of alternative genetic codes, showing that SGC is nearly optimal for frameshift tolerance. In many genes and certain genomes, frameshift-resistant codons and codon pairs appear more frequently than expected, suggesting that frameshift tolerance is achieved through not only the optimality of the genetic code but, more importantly, the further optimization of a specific gene or genome through the usages of codons/codon pairs, which sheds light on the role of frameshift mutations in molecular and genomic evolution.

Single-Cell Identification, Drug Susceptibility Test, and Whole-genome Sequencing of Helicobacter pylori Directly from Gastric Biopsy by Clinical Antimicrobial Susceptibility Test Ramanometry.

BACKGROUND: The battle against Helicobacter pylori (H. pylori) infections demands fast, reliable, and sensitive methods for pathogen identification (ID), antimicrobial susceptibility tests (ASTs) based on metabolic response, and genome-wide mutation profiling that reveals resistance mechanisms. METHODS: Here we introduce Clinical Antimicrobial Susceptibility Test Ramanometry for H. pylori (CAST-R-HP), and its validation with clinical samples. This method performs rapid ID, metabolism inhibition-based AST, and high-quality whole-genome sequencing for cells of targeted resistance phenotype, all at precisely 1-cell resolution and directly from biopsy samples. RESULTS: In CAST-R-HP, automated acquisition and machine learning of single-cell Raman spectra (SCRS) enable distinguishing individual H. pylori cells directly from a biopsy sample, with 98.5 ± 0.27% accuracy in ID. Moreover, by adding a 48- to72-h D2O feeding and drug exposure step prior to SCRS acquisition, CAST-R-HP reports AST for levofloxacin and clarithromycin with 100% accuracy, based on metabolic inhibition level. Furthermore, CAST-R-HP supports rapid sorting, low-bias DNA amplification, and full genome sequencing of single H. pylori cells with the SCRS defined, targeted drug-susceptibility phenotype, via Raman-activated gravity-driven cell encapsulation and sequencing. The genome-wide mutation map (maximum 99.70% coverage), at precisely 1-cell resolution, not only elucidates the drug-susceptibility phenotypes but also unveils their underlying molecular mechanisms. CONCLUSION: The culture independency, shorter turnaround time, high resolution, and comprehensive information output suggest that CAST-R-HP is a powerful tool for diagnosing and treating H. pylori infections.

Intrinsic specificity of plain ammonium citrate carbon dots for Helicobacter pylori: Interfacial mechanism, diagnostic translation and general revelation.

The exploitation of carbon dots (CDs) is now flourishing; however, more effort is needed to overcome their lack of intrinsic specificity. Herein, instead of synthesizing novel CDs, we reinvestigated three reported CDs and discovered that plain ammonium citrate CDs (AC-CDs) exhibited surprising specificity for Helicobacter pylori. Notably, we showed that the interfacial mechanism behind this specificity was due to the affinity between the high abundant urea/ammonium transporters on H. pylori outer membrane and the surface-coordinated ammonium ions on AC-CDs. Further, we justified that ammonium sulfate-citric acid CDs also possessed H. pylori-specificity owing to their NH4 + doping. Thereby, we suggested that the incorporation of a molecule that could be actively transported by abundant membrane receptors into the precursors of CDs might serve as a basis for developing a plain CD with intrinsic specificity for H. pylori. Moreover, AC-CDs exhibited specificity towards live, dead, and multidrug-resistant H. pylori strains. Based on the specificity, we developed a microfluidics-assisted in vitro sensing approach for H. pylori, achieving a simplified, rapid and ultrasensitive detection with two procedures, shortened time within 45.0 â€‹min and a low actual limit of detection of 10.0 â€‹CFU â€‹mL-1. This work sheds light on the design of more H. pylori-specific or even bacteria-specific CDs and their realistic translation into clinical practice.

Bacteria-targeting chitosan/carbon dots nanocomposite with membrane disruptive properties improve eradication rate of Helicobacter pylori.

We designed a bacteria-targeting and membrane disrupting nanocomposite for successful antibiotic treatment of Helicobacter pylori (H. pylori) infections in the present study. The antibacterial nanocomposite was prepared from thiolated-ureido-chitosan (Cys-U-CS) and anionic poly (malic acid) (PMLA) via electrostatic interaction decorated with dual functional ammonium citrate carbon quantum dots (CDs). Cys-U-CS serves as a targeting building block for attaching antibacterial nanocomposite onto bacterial cell surface through Urel-mediated protein channel. Simultaneously, membrane disrupting CDs generate ROS and lyse the bacterial outer membrane, allowing antibiotics to enter the intracellular cytoplasm. As a result, Cys-U-CS/PMLA@CDs nanocomposite (UCPM-NPs) loaded with the antibiotic amoxicillin (AMX) not only effectively target and kill bacteria in vitro via Urel-mediated adhesion but also efficiently retain in the stomach where H. pylori reside, serving as an effective drug carrier for abrupt on-site release of AMX into the bacterial cytoplasm. Furthermore, since thiolated-chitosan has a mucoadhesive property, UCPM-NPs may adhere to the stomach mucus layer and pass through it swiftly. According to our results, bacterial targeting is crucial for guaranteeing successful antibiotic treatment. The bacteria targeting UCPM-NPs with membrane disruptive ability may establish a promising drug delivery system for the effective targeted delivery of antibiotics to treat H. pylori infections.

Overgrowth of Lactobacillus in gastric cancer.

Dysbiosis of the gastric microbiome is involved in the development of gastric cancer (GC). A number of studies have demonstrated an increase in the relative abundance of Lactobacillus in GC. In this review, we present data that support the overgrowth of Lactobacillus in GC from studies on molecular and bacterial culture of the gastric microbiome, discuss the heterogenic effects of Lactobacillus on the health of human stomach, and explore the potential roles of the overgrowth of Lactobacillus in gastric carcinogenesis. Further studies are required to examine the association between Lactobacillus and GC at strain and species levels, which would facilitate to elucidate its role in the carcinogenic process.

Aptamer-superparamagnetic nanoparticles capture coupling siderophore-Fe3+ scavenging actuated with carbon dots to confer an "off-on" mechanism for the ultrasensitive detection of Helicobacter pylori.

The detection of Helicobacter pylori infection in human feces is an appropriate non-invasive diagnostic method. However, the antibody-dependent stool antigen immunoassay bears many challenges. Therefore, we developed an antibody-independent biosensing platform. The core of this platform was a triple-module biosensor. The first module was Ca2+-doped superparamagnetic nanoparticles modified with an H. pylori-specific aptamer, functioning to selectively capture H. pylori cells from samples. The second module was a bifunctional co-polymer of chloroprotoporphyrin IX iron (III)-polyethylene glycol-desferrioxamine, which could bind to H. pylori with high affinity and chelate Fe3+ from the third module of Fe3+-quenched carbon dots (CDs) solution. When the formed module 1-H. pylori-module 2 complexes reacted with module 3, a subsequent magnetic separation could scavenge Fe3+, causing fluorescence recovery from quenched CDs as the transducing mechanism. This transducer could respond to tiny changes in Fe3+ concentration with distinguishable fluorescence differences, thus conferring the biosensor with high sensitivity, a wide detection range of 10-107 CFU/mL and a limit of detection (LOD) as low as 1 CFU/mL. From simulated human stool samples, H. pylori was enriched with a centrifugal microfluidic plate to eliminate any interference from matrices, and the bacteria were subjected to detection using the biosensor. The actual LOD for the biosensing platform coupling microfluidics and the biosensor was 101, and the total time taken was 65 min. This work showcases an instant, accurate, and ultra-sensitive diagnosis of H. pylori in feces.

Cytotoxic xanthones from the plant endophytic fungus Paecilamyces sp. TE-540.

One new xanthone, chryxanthone C (1), together with four known analogues (2-5), were isolated from the cultures of Paecilamyces sp. TE-540, an endophytic fungus obtained from the leaves of Nicotiana tabacum L. The structure of 1 was elucidated by comprehensive spectral analysis including HRESIMS and 1D/2D NMR, which were confirmed by Cu Kα X-ray crystallography. Compound 1 featured an unusual dihydropyran ring fused to an aromatic ring, rather than the commonly occurring prenyl moiety. The cytotoxicity of compounds 1-5 were evaluated against five human tumour cell lines and 4 exhibited moderate to strong cytotoxicities with IC50 values ranging from 5.6 to 14.2 µM.

Signatures of Mucosal Microbiome in Oral Squamous Cell Carcinoma Identified Using a Random Forest Model.

OBJECTIVE: The aim of this study was to explore the signatures of oral microbiome associated with OSCC using a random forest (RF) model. PATIENTS AND METHODS: A total of 24 patients with OSCC were enrolled in the study. The oral microbiome was assessed in cancerous lesions and matched paracancerous tissues from each patient using 16S rRNA gene sequencing. Signatures of mucosal microbiome in OSCC were identified using a RF model. RESULTS: Significant differences were found between OSCC lesions and matched paracancerous tissues with respect to the microbial profile and composition. Linear discriminant analysis effect size analyses (LEfSe) identified 15 bacteria genera associated with cancerous lesions. Fusobacterium, Treponema, Streptococcus, Peptostreptococcus, Carnobacterium, Tannerella, Parvimonas and Filifactor were enriched. A classifier based on RF model identified a microbial signature comprising 12 bacteria, which was capable of distinguishing cancerous lesions and paracancerous tissues (AUC = 0.82). The network of the oral microbiome in cancerous lesions appeared to be simplified and fragmented. Functional analyses of oral microbiome showed altered functions in amino acid metabolism and increased capacity of glucose utilization in OSCC. CONCLUSION: The identified microbial signatures may potentially be used as a biomarker for predicting OSCC or for clinical assessment of oral cancer risk.

Gastric Mucosa-Associated Microbial Signatures of Early Gastric Cancer.

Alterations in the microbiome are associated with the development of gastric cancer. Our study aimed to identify dysbiotic features in early gastric cancer (EC). The gastric microbiome was assessed in EC (n = 30), advanced gastric cancer (AC) (n = 30), and chronic gastritis (CG) (n = 60). The results demonstrated significant differences in the microbial profile and composition between EC and AC, suggesting alterations associated with gastric cancer progression. Linear discriminant analysis (LDA) effect size (LEfSe) analyses identified 32 bacterial genera that were associated with EC. Functional analyses of the gastric microbiome showed that the production of urease and synthesis of bacterial flagella were weakened in EC, while the glycolysis of fructose and hydrolysis of glycosides were enhanced. A classifier based on a random forest (RF) machine learning algorithm identified a microbial signature that distinguished EC from CG or AC with high accuracy. The correct identification of the signature was further validated in independent cohorts. This signature enriched of bacteria with varied abundance, high degree of bacterial interactions and carcinogenic potentials. Constrained principal coordinate analyses revealed that the presence of Helicobacter pylori and the cagA and vacA virulence genotypes influenced the structure of the gastric microbiome. To determine the impacts of host genetic variations on the gastric microbiome, six previously reported single nucleotide polymorphisms (SNPs) were examined. The minor allele of MUC1 rs4072037 was associated with an increased abundance of Ochrobactrum. The gastric microbiome altered in EC, which might be attributed in part to host genetic variations, H. pylori infection, bacterial virulence and environmental adaptations. The identified microbial signature could serve as biomarkers for clinical assessment of gastric cancer risk in high-risk patients.

Gastric hyperplastic polyps inversely associated with current Helicobacter pylori infection.

The incidence of gastric hyperplastic polyps (HPs) has been on the rise in recent years. The contribution of Helicobacter pylori infection to this trend has remained to be elucidated. The present study aimed to explore the association between HPs and H. pylori in China, an area with a high infection rate of H. pylori. In order to study trends of HPs and H. pylori infection over the past decades, cases encountered from 2009 to 2018 were assessed and a total of 109,150 consecutive patients who underwent esophagogastroduodenoscopy at Qingdao Municipal Hospital (Qingdao, China) were enrolled. The incidence of HPs and the prevalence of H. pylori were determined and their correlation was explored. Gastric HPs were detected in 1,497 patients (1.6%) who received gastric biopsies. The incidence of HPs exhibited a rising trend, with a ~4-fold increase in the annual detection rate from 2009 to 2018. The prevalence of H. pylori infection was inversely associated with the prevalence of HPs (adjusted odds ratio, 0.66). The prevalence of H. pylori in the examined cohort decreased with time (r=-0.76, P=0.011). The decreasing trend of H. pylori infection was negatively correlated with the rising trend of HPs (r=-0.64, P=0.048), further indicating an inverse association between them. The difference in the prevalence of HPs between H. pylori-negative and -positive patients increased with age (r=0.80, P=0.018). The age-associated increase was slower in H. pylori-infected patients. The decline in H. pylori infection with time appeared to not be associated with the birth cohort effect, suggesting the decline was not caused by exposure to environmental factors during an early period of life. The present results indicated that the incidence of gastric HPs increased with the decline in H. pylori infection, demonstrating an inverse association between the occurrence of HPs and the infection.

Association of Nonalcoholic Fatty Liver Disease and Coronary Artery Disease with FADS2 rs3834458 Gene Polymorphism in the Chinese Han Population.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) patients are often prone to coronary artery disease (CAD), and CAD is found to be the main cause of death in NAFLD patients. The purpose of this study was to investigate the association between fatty acid desaturase 2 (FADS2) rs3834458 polymorphism and serum FADS2 level with NAFLD and CAD in Chinese Han population. MATERIALS AND METHODS: The serum level of FADS2 was detected by enzyme-linked immunosorbent assay (ELISA) in healthy people, NAFLD patients, and NAFLD patients combined with CAD (NAFLD+CAD). Polymerase chain reaction (PCR) was used to detect the genotypes of FADS2 rs3834458 in the three groups. RESULTS: Body mass index (BMI), glucose (GLU), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) of the NAFLD group and the NAFLD+CAD group were higher than those of the healthy control group (P < 0.05); the HDL-C of the NAFLD+CAD group was significantly lower than that of the healthy people and the NAFLD group (P < 0.05). The serum FADS2 concentration in the NAFLD+CAD group was significantly higher than that in the NAFLD group (P < 0.05) and the healthy people (P < 0.05). There was no significant difference in genotype distribution (χ 2 = 5.347, P < 0.497) and allele frequency (χ 2 = 3.322, P = 0.345) between the three groups. Logistic regression analysis showed that the T allele was not an independent risk factor for CAD with NAFLD (OR = 1.62, 95% CI: 0.422-6.180). CONCLUSIONS: Serum FADS2 concentration was positively correlated with the susceptibility of NAFLD with CAD, while the polymorphism of rs3834458 was not associated with NAFLD with CAD.

Role and effective therapeutic target of gut microbiota in NAFLD/NASH.

Non-alcoholic fatty liver disease (NAFLD), the most prevalent chronic liver disease in the world, is affected by numerous extrinsic and intrinsic factors, including lifestyle, environment, diet, genetic susceptibility, metabolic syndrome and gut microbiota. Accumulating evidence has proven that gut dysbiosis is significantly associated with the development and progression of NAFLD, and several highly variable species in gut microbiota have been identified. The gut microbiota contributes to NAFLD by abnormal regulation of the liver-gut axis, gut microbial components and microbial metabolites, and affects the secretion of bile acids. Due to the key role of the gut microbiota in NAFLD, it has been regarded as a potential target for the pharmacological and clinical treatment of NAFLD. The present review provides a systematic summary of the characterization of gut microbiota and the significant association between the gut microbiota and NAFLD. The possible mechanisms of how the gut microbiota is involved in promoting the development and progression of NAFLD were also discussed. In addition, the potential therapeutic methods for NAFLD based on the gut microbiota were summarized.

Salidroside suppresses the metastasis of hepatocellular carcinoma cells by inhibiting the activation of the Notch1 signaling pathway.

Salidroside (SDS) is a phenylpropanoid glycoside isolated from Rhodiola rosea L. It exhibits multiple pharmacological properties in clinical medicine and has been commonly used in traditional Chinese medicine. The present study investigated the inhibitory effects of SDS on tumor invasion and migration, and the expression of metastasis­related genes in highly metastatic hepatocellular carcinoma (HCC) cells (MHCC97H) in vitro. The underlying mechanisms of SDS on the tumor metastasis were also explored. SDS was found to significantly reduce wound closure areas and inhibit cell migration. In addition, SDS markedly inhibited the invasion of these cells into Matrigel­coated membranes. SDS markedly downregulated the expression of Notch1, Snail, COX­2, MMP­2, MMP­9 genes and upregulated the expression of E­cadherin in a dose­dependent manner. Furthermore, SDS inhibited the expression of the Notch signaling target genes, Hey1, Hes1 and Hes5. On the whole, the findings of this study suggest that SDS inhibits HCC cell metastasis by modulating the activity of the Notch1 signaling pathway.

Diagnostic value of MRI-PDFF for hepatic steatosis in patients with non-alcoholic fatty liver disease: a meta-analysis.

OBJECTIVE: To systematically review studies about the diagnostic accuracy of magnetic resonance imaging proton density fat fraction (MRI-PDFF) in the classification of hepatic steatosis grade in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: Areas under the summary receiver operating characteristic curves (AUROC), sensitivity, specificity, overall diagnostic odds ratio (DOR), diagnostic score, positive likelihood ratio (+LR), and negative likelihood ratio (-LR) for MRI-PDFF in classification of steatosis grades 0 vs. 1-3, 0-1 vs. 2-3, and 0-2 vs. 3 were compared and analyzed. RESULTS: A total of 6 studies were included in this meta-analysis (n = 635). The summary AUROC values of MRI-PDFF for classifying steatosis grades 0 vs. 1-3, 0-1 vs. 2-3, and 0-2 vs. 3 were 0.98, 0.91, and 0.90, respectively. Pooled sensitivity and specificity of MRI-PDFF for classifying steatosis grades 0 vs. 1-3, 0-1 vs. 2-3, and 0-2 vs. 3 were 0.93 and 0.94, 0.74 and 0.90, and 0.74 and 0.87, respectively. Summary +LR and -LR of MRI-PDFF for classifying steatosis grades 0 vs. 1-3, 0-1 vs. 2-3, and 0-2 vs. 3 were 16.21 (95%CI, 4.72-55.67) and 0.08 (95%CI, 0.04-0.15), 7.19 (95%CI, 5.04-10.26) and 0.29 (95%CI, 0.22-0.38), and 5.89 (95%CI, 4.27-8.13) and 0.29 (95%CI, 0.21-0.41), respectively. CONCLUSIONS: Our meta-analysis suggests that MRI-PDFF has excellent diagnostic value for assessment of hepatic fat content and classification of histologic steatosis in patients with NAFLD. KEY POINTS: • MRI-PDFF has significant diagnostic value for hepatic steatosis in patients with NAFLD. • MRI-PDFF may be used to classify grade of hepatic steatosis with high sensitivity and specificity.

Ureido-modified carboxymethyl chitosan-graft-stearic acid polymeric nano-micelles as a targeted delivering carrier of clarithromycin for Helicobacter pylori: Preparation and in vitro evaluation.

The effect of antibiotics in the stomach for curing Helicobacter pylori infection is hampered by the adverse gastric environment and low bioavailability of the administered drugs. Concerning these challenges, a polymeric nano-micelle was developed. Initially, carboxymethyl chitosan (CMCS) was hydrophobically modified with stearic acid (SA), and the obtained CMCS-g-SA co-polymers was further conjugated with urea to acquire U-CMCS-g-SA co-polymers. Sphere-shaped nano-micelles (UCS-NMs) with the particle sizes of approximately 200nm were obtained with the U-CMCS-g-SA co-polymers. It was specified that this nano-micelle had no cell toxicity to AGS cells, and it could maintain a stable particle size for 6h in simulated gastric fluid and for 24h in 1×PBS. Attractively, the CMCS backbones granted this nano-micelle an excellent retention time in the stomach, almost 24h; meanwhile, the grafted ureido groups conferred effective targeting to H. pylori. This nano-micelle could load clarithromycin with high efficiency and exhibited slow release of this antibiotic in a slightly alkaline environment. In vitro inhibitory assay also indicated that a significantly enhanced anti-H. pylori activity was achieved by using this nano-micelle. This work demonstrated that the U-CMCS-g-SA nano-micelle is a proper carrier for targeted delivery of clarithromycin to H. pylori under the gastric mucus layer.