Characterization of linezolid- and methicillin-resistant coagulase-negative staphylococci in a tertiary hospital in China.

BACKGROUND: Recently, linezolid-resistant staphylococci have become an emerging problem worldwide. Understanding the mechanisms of resistance, molecular epidemiology and transmission of linezolid-resistant CoNS in hospitals is very important. METHODS: The antimicrobial susceptibilities of all isolates were determined by the microdilution method. The resistance mechanisms and molecular characteristics of the strains were determined using whole-genome sequencing and PCR. RESULTS: All the strains were resistant to oxacillin and carried the mecA gene; 13 patients (36.1%) had prior linezolid exposure. Most S. epidermidis and S. hominis isolates were ST22 and ST1, respectively. MLST typing and evolutionary analysis indicated most linezolid-resistant CoNS strains were genetically related. In this study, we revealed that distinct CoNS strains have different mechanisms of linezolid resistance. Among ST22-type S. epidermidis, acquisition of the T2504A and C2534T mutations in the V domain of the 23 S rRNA gene, as well as mutations in the ribosomal proteins L3 (L101V, G152D, and D159Y) and L4 (N158S), were linked to the development of linezolid resistance. In S. cohnii isolates, cfr, S158Y and D159Y mutations in the ribosomal protein L3 were detected. Additionally, emergence of the G2576T mutation and the cfr gene were major causes of linezolid resistance in S. hominis isolates. The cfr gene, G2576T and C2104T mutations, M156T change in L3 protein, and I188S change in L4 protein were found in S. capitis isolates. CONCLUSION: The emergence of linezolid-resistant CoNS in the environment is concerning because it involves clonal dissemination and frequently coexists with various drug resistance mechanisms.

Association of SULT1A2 rs1059491 with obesity and dyslipidaemia in southern Chinese adults.

In the sulfotransferase (SULT) superfamily, members of the SULT1 family mainly catalyse the sulfonation reaction of phenolic compounds, which is involved in the phase II metabolic detoxification process and plays a key role in endocrine homeostasis. A coding variant rs1059491 in the SULT1A2 gene has been reported to be associated with childhood obesity. This study aimed to investigate the association of rs1059491 with the risk of obesity and cardiometabolic abnormalities in adults. This case‒control study included 226 normal weight, 168 overweight and 72 obese adults who underwent a health examination in Taizhou, China. Genotyping of rs1059491 was performed by Sanger sequencing in exon 7 of the SULT1A2 coding region. Chi-squared tests, one-way ANOVA, and logistic regression models were applied. The minor allele frequencies of rs1059491 in the overweight combined with obesity and control groups were 0.0292 and 0.0686, respectively. No differences in weight and body mass index were detected between the TT genotype and GT + GG genotype under the dominant model, but the levels of serum triglycerides were significantly lower in G-allele carriers than in non-G-allele carriers (1.02 (0.74-1.32) vs. 1.35 (0.83-2.13) mmol/L, P = 0.011). The GT + GG genotype of rs1059491 versus the TT genotype reduced the risk of overweight and obesity by 54% (OR 0.46, 95% CI 0.22-0.96, P = 0.037) after adjusting for sex and age. Similar results were observed for hypertriglyceridaemia (OR 0.25, 95% CI 0.08-0.74, P = 0.013) and dyslipidaemia (OR 0.37, 95% CI 0.17-0.83, P = 0.015). However, these associations disappeared after correction for multiple tests. This study revealed that the coding variant rs1059491 is nominally associated with a decreased risk of obesity and dyslipidaemia in southern Chinese adults. The findings will be validated in larger studies including more detailed information on genetic background, lifestyle and weight change with age.

Is Intermittent Fasting Better Than Continuous Energy Restriction for Adults with Overweight and Obesity?

As a popular weight management intervention, intermittent fasting (IF) has been widely applied to the treatment of overweight and obesity in adults. This review describes the different forms and implementation protocols of IF and their effects on body weight, body composition, cardiometabolic risk factors and other diseases. The existing evidence suggests that IF is as effective as continuous energy restriction and may be a feasible and effective approach to weight loss.

Association of Helicobacter pylori infection with osteoporosis risk in a physical examination population.

The association between Helicobacter pylori (H. pylori) infection and osteoporosis risk remains equivocal. Our findings showed that H. pylori infection appears to have no effect on the risk of osteopenia and osteoporosis. Weight status may modify the association of H. pylori infection with low bone mass. PURPOSE: To evaluate the association between baseline H. pylori infection and osteoporosis risk in the general population. METHODS: From January 1, 2019, to March 31, 2020, 1388 women and men aged over 50 years underwent a health examination. H. pylori infection was detected by the 13C urea breath test. Subjects were classified as having normal bone mineral density (BMD), osteopenia, and osteoporosis according to dual-energy X-ray absorptiometry. Chi-square tests and multinomial logistic regression models were performed to analyze the associations of H. pylori infection with osteopenia and osteoporosis. RESULTS: Of the 1388 participants, 545 (39.3%) were H. pylori-positive. The prevalence rates of osteoporosis and osteopenia were 10.2% and 32.3%, respectively. No differences were observed in the rates of osteoporosis and osteopenia between H. pylori-positive and H. pylori-negative groups (P > 0.05). The association for the trend between the H. pylori infection and osteoporosis was only seen in the nonoverweight subgroup (trend χ2 = 5.455, P = 0.02). The odds ratio (OR) between H. pylori infection and osteoporosis was 1.31 (95% CI, 0.86-2.02, P = 0.211) after adjusting for sex, age, and body weight status. CONCLUSIONS: We demonstrate that H. pylori infection is not an independent risk factor for osteopenia and osteoporosis. This study did not support the association of H. pylori infection with osteoporosis.

Persistent infection of Helicobacter pylori affects weight loss in obese population compared with persistent negative: A case-control study based on healthy Chinese.

BACKGROUND: The relationship between Helicobacter pylori (H pylori) and body mass index (BMI) is still inconclusive. Not only the high rate of H pylori infection but also the increasing higher BMI levels are endangering Chinese today. METHODS: The aim of this research was to evaluate the association between different situations of H pylori infection and BMI values or levels in Chinese healthy population. A total of 39 091 individuals aged from 18 years to 80 years, performed healthy examination including a 13 C/14 C urease breath test (13 C/14 C-UBT), were included. Among them, 30 224 individuals only had one time of health examination, and 8867 had two or more times. A case-cohort data of 8752 with an interval time more than 6 months, collected by the first and the last time, were established from the latter. BMI groups are classified according to the China recommendation: low weight (<18.5 kg/m2 ), normal weight (18.5 ~ 23.9 kg/m2 ), overweight (24.0 ~ 27.9 kg/m2 ), and obesity (≥28.0 kg/m2 ). RESULTS: The rate of H pylori infection among low weight, normal weight, overweight, and obesity was 43.2%, 44.7%, 46.4%, and 48.0%, respectively (P = .000). H pylori infection increased the risk of higher level of BMI (OR = 1.077, 95% confidence interval = 1.036-1.119, χ2  = 14.048, P = .000) with adjustments for sex and age. In the case-control study, the rate of persistent negative, persistent infection, new infection, and eradicated infection was 39.5%, 25.8%, 15.8%, and 18.9%, respectively, with a median interval time of 13 months. The mean obesity BMI descend values in the persistent negative subgroup were lower than those in the persistent infection subgroup (-0.21 ± 1.19 kg/m2 vs -0.003 ± 1.01 kg/m2 , P = .021). But the change of BMI classifications had no difference between the subgroups of H pylori infection in different BMI levels. CONCLUSIONS: H pylori infection was positively correlated with higher BMI levels. And H pylori persistent infection had a negative effect on the fall of BMI values in Chinese obese population.

The emergence of Staphylococcus epidermidis simultaneously nonsusceptible to linezolid and teicoplanin in China.

Two linezolid-resistant and teicoplanin-intermediate Staphylococcus epidermidis strains were isolated from blood cultures in China. The 2 S. epidermidis strains were methicillin-resistant and showed multidrug-resistance patterns; in addition, population analysis profiling/area under the curve (PAP/AUC) result showed heterogeneous resistant to vancomycin. Comparing to teicoplanin susceptible strains, the 2 isolates showed reduced autolytic activity. Pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) indicated that the 2 S. epidermidis isolates belonged to the same clone. Furthermore, the cfr gene, a G2576T mutation, and a novel C2146T mutation were detected in the 2 isolates. This was the first report of S. epidermidis simultaneously nonsusceptible to linezolid and teicoplanin in China.

HOXD-AS1 confers cisplatin resistance in gastric cancer through epigenetically silencing PDCD4 via recruiting EZH2.

Increasing evidence suggests that dysregulation of long non-coding RNAs (lncRNAs) is implicated in chemoresistance in cancers. However, the function and molecular mechanisms of lncRNAs in gastric cancer chemoresistance are still not well understood. In this study, we aimed to investigate the functional role and the underlying molecular mechanisms of lncRNA HOXD cluster antisense RNA 1 (HOXD-AS1) in cisplatin (DDP) resistance in gastric cancer. Our results revealed that HOXD-AS1 was upregulated in DDP-resistant gastric cancer tissues and cells. Patients with gastric cancer with high HOXD-AS1 expression levels had a poor prognosis. Knockdown of HOXD-AS1 facilitated the sensitivity of DDP-resistant gastric cancer cells to DDP. Additionally, HOXD-AS1 epigenetically silenced PDCD4 through binding to the histone methyltransferase enhancer of zeste homologue 2 (EZH2) on the promoter of PDCD4, thus increasing H3K27me3. More importantly, PDCD4 silencing counteracted HOXD-AS1 knockdown-mediated enhancement of DDP sensitivity in DDP-resistant gastric cancer cells. In summary, HOXD-AS1 led to DDP resistance in gastric cancer by epigenetically suppressing PDCD4 expression, providing a novel therapeutic strategy for patients with gastric cancer with chemoresistance.

Long noncoding RNA FEZF1-AS1 promotes the motility of esophageal squamous cell carcinoma through Wnt/ß-catenin pathway.

Background: Long noncoding RNAs (lncRNAs), a class of noncoding RNA nucleotides >200 bp, has been demonstrated to play vital role in the development of cancer. FEZ family zinc finger 1 antisense RNA 1 (FEZF1-AS1) has been reported as an lncRNA which acts as a tumor-promoting effect in some cancers. However, the role of it in esophageal squamous cell carcinoma (ESCC) and its potential regulatory mechanism was unclear now. Methods: qRT-PCR was used to detect the levels of FEZF1-AS1 and mRNA CTNNB1 (ß-catenin) in ESCC tissues and cells. Cell transfection experiments were used to knock down or overexpress the level of FEZF1-AS1 in EC1 and EC9706 cell lines. WST-1 assays, cell cycle assays, scratch wound assays, migration, and invasion assays were used to evaluate the function of FEZF1-AS1 in ESCC progression. Results: FEZF1-AS1 was remarkably upregulated in ESCC tissues and cell lines. Silencing of FEZF1-AS1 significantly inhibited the migration and invasion of ESCC cells, while overexpression of FEZF1-AS1 notably accelerated ESCC migration and invasion. Meanwhile, the levels of FEZF1-AS1 had no effect on ESCC cell proliferation and cell cycle. We also found that ß-catenin was upregulated in ESCC tissues, and the level of it was positively correlated with the expression of FEZF1-AS1. Silencing of FEZF1-AS1 could decrease the mRNA and protein level of ß-catenin, while overexpression FEZF1-AS1 could lead to the contrary. Conclusion: Our results suggested that the expression of lncRNA FEZF1-AS1 played an important role in ESCC progression, especially the motility of the tumor. FEZF1-AS1 may provide us with a new sight for ESCC treatment.

Construction of a long non-coding RNA-associated ceRNA network reveals potential prognostic lncRNA biomarkers in hepatocellular carcinoma.

OBJECTIVES: Hepatocellular carcinoma (HCC) is the sixth leading cause of cancer-related mortality in the world. Accumulating evidence has highlighted the regulatory roles of long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) in HCC. METHODS: The lncRNA expression data and corresponding patient information were obtained from The Cancer Genome Atlas (TCGA) database. Competing lncRNA-mRNA interactions were identified using the hypergeometric test. Co-expression analysis was implemented using the Spearman correlation coefficient. Multivariate Cox regression survival analysis was utilized to extract prognostic lncRNAs in the network. RESULTS: Based on the "ceRNA hypothesis", a global lncRNA-associated ceRNA network (LCeNET) in HCC was constructed. Nine lncRNAs were identified as hubs and found to be enriched in various cancer-related biological processes. In addition, ceRNA pairs associated with survival were screened to construct a lncRNA-miRNA-mRNA sub network. Finally, we developed a sixteen-lncRNA model that could classify patients into high- and low-risk subgroups with different survival outcomes, and MCM3AP-AS1 functioned as a hub in both LCeNET and prognostic model. CONCLUSIONS: Our work will improve the understanding of lncRNA-mediated ceRNA regulatory mechanisms in HCC pathogenesis and facilitate the identification of candidate prognostic biomarkers for HCC.

Linc00472 suppresses proliferation and promotes apoptosis through elevating PDCD4 expression by sponging miR-196a in colorectal cancer.

Long intergenic non-coding RNA Linc00472 has been considered as a tumor suppressor in some cancers. However, the function and mechanism of Linc00472 in colorectal cancer has not been well elucidated. In this study, we found that Linc00472 was down-regulated in colorectal cancer tissues and cells. Elevated Linc00472 expression suppressed proliferation and induced apoptosis in colorectal cancer cells. Moreover, Linc00472 acted as a competing endogenous RNA (ceRNA) of miR-196a to release programmed cell death 4 (PDCD4). Furthermore, miR-196a overexpression or PDCD4 knockdown reversed Linc00472-mediated proliferation inhibition and apoptosis induction in colorectal cancer cells. Ectopic Linc00472 expression hindered tumor growth in vivo. Our study demonstrated that Linc00472 suppressed proliferation and induced apoptosis through up-regulating PDCD4 by decoying miR-196a, which may be an effective therapeutic target for colorectal cancer.

Mechanism for carbapenem resistance of clinical Enterobacteriaceae isolates.

Carbapenemase-producing 'super bacteria', particularly NDM-1 and its variants, have become a major public health concern worldwide. The present study aimed to explore the molecular mechanism for carbapenem resistance of clinical Enterobacteriaceae isolates. Seventy-eight non-repeated Enterobacteriaceae strains resistant to any carbapenem were screened at the First Affiliated Hospital of Zhengzhou University (Zhengzhou, China) between December 2011 and December 2015. Outer membrane porin (OMP) proteins were detected using SDS-PAGE. Carbapenemases, extended-spectrum ß-lactamases (ESBLs) and plasmid AmpC enzyme genes were detected using polymerase chain reaction (PCR). PCR and SDS-PAGE demonstrated that 60.3% (47/78) of the strains produced carbapenemases, of which 33.3% (26/78) produced KPC-2 carbapenemase, suggesting that the strains resisted carbapenems primarily through carbapenemases. SDS-PAGE showed that the OMP proteins in the majority of carbapenem-resistant Enterobacteriaceae (CRE) strains were deleted or decreased compared with those in the sensitive strains. Of the 44 Klebsiella strains, 59.1% (26/44) did not express or expressed less OmpK35 or OmpK36. Among the 34 strains of other enterobacteria, 97.1% (33/34) did not express or expressed less OmpC or OmpF. Of all CRE strains, 35.9% (28/78) lost at least one OMP protein, indicating that the strains resisted carbapenems also by producing ESBLs and/or plasmid AmpC enzyme, as well as by losing OMP proteins. The resistance of clinically isolated CRE strains may primarily be attributed to the production of carbapenemases, and may also involve the deletion of OMP proteins or mutation of OMP genes.

Exosomes participate in the carcinogenesis and the malignant behavior of gastric cancer.

OBJECTIVE: In order to summarize the role of exosomes in invasion and metastasis in gastric cancer (GC). MATERIAL: Exosomes are vesicles of endocytic origin ranging from 30 to 100 nm in size; they are composed of a lipid bilayer and contain DNA, mRNA, miRNA, circular RNA and multiple proteins. Recently, increasing evidence shows that exosomes play a crucial role in the tumorigenesis of GC. RESULTS: In this review, we focus on the latest findings on GC exosomes, mainly summarizing their role in invasion and metastasis in GC. Then, exosomes? potential functions as novel diagnostic and therapeutic biomarkers for GC are briefly discussed. At last, we prospect the clinical application perspective of exosomes in GC. CONCLUSIONS: Exosomes play a vital role in gastric cancer carcinogenesis and metastasis.