Exposure to trace levels of live seaweed-derived antibacterial 2,4,6-tribromophenol modulates ß-lactam antibiotics resistance in Vibrio.

Non-antibiotic substances have been found to contribute to the spread of antibiotic resistance. Bromophenols (BPs) are special anti-bacterial substances obtained from seaweed. This study explored the modulatory effect of trace BPs from a live seaweed on the antibiotic resistance of pathogenic Vibrio (V.) strains. A hydroponic solution of Ulva fasciata was found to contain trace levels (9-333 µg L-1) of 2,4,6-tribromophenol (TBP), a typical BP. TBP at a concentration of 165 µg L-1 significantly increased the inhibition zone diameter of widely used ß-lactam antibiotics (amoxicillin and ampicillin) against V. alginolyticus M7 (Va. M7) and V. parahaemolyticus M3 (Vp. M3) as well as reduced the minimum inhibitory concentration by 2-4 fold against Va. M7. Whole genome re-sequencing analysis demonstrated that Va. M3 (53-60) had more mutant genes than Vp. M7 (44) in ß-lactam resistance pathway. Transcriptome sequencing analysis, along with verification through RT-qPCR, further showed that oligopeptide permease (opp) was the only differentially expressed gene (DEG) among the mutated genes in the ß-lactam resistance pathway. The opp transport activity and membrane permeability of Vibrio were both enhanced at 165 µg L-1 of TBP, and the ability of biofilm formation was also decreased. Thus, antibiotics resistance improvement of Vibrio by TBP was potentially related with the promoted opp transport activity, membrane permeability and inhibited biofilm formation.

PLAGL2 Promotes the Proliferation and Migration of Diffuse Large B-cell Lymphoma Cells via Wnt/ß-catenin Pathway.

OBJECTIVE: Pleomorphic adenoma gene like-2 (PLAGL2) belongs to PLAG protein family and functions as a zinc finger transcriptional factor to participate in the cellular processes, including cell transformation, migration, and apoptosis. Increasing evidence has shown the oncogenic role of PLAGL2 in various cancers, while the potential molecular mechanism and biology roles of PLAGL2 in diffuse large B-cell lymphoma (DLBCL) are still unclear. METHODS: Expression of PLAGL2 was found to be elevated in DLBCL cells. Functional assays showed that silence of PLAGL2 suppressed cell proliferation and reduced the cell migration and invasion in DLBCL. The cell proliferation and metastasis in DLBCL were promoted by over-expression of PLAGL2. Moreover, the protein expression of E-cadherin was increased, while the protein expressions of N-cadherin and vimentin were decreased in DLBCL cells by knockdown of PLAGL2. However, over-expression of PLAGL2 promoted epithelial to mesenchymal transition (EMT) of DLBCL through down-regulation of E-cadherin, and up-regulations of N-cadherin and vimentin. RESULTS: Over-expression of PLAGL2 up-regulated ß-catenin and c-myc, while down-regulated axis inhibition protein 2 (AXIN2) and adenomatous polyposis coli (APC) in DLBCL. Knockdown of PLAGL2 suppressed the activation of Wnt/ß-catenin pathway in DLBCL through downregulating ß-catenin and c-myc but upregulating AXIN2 and APC. Xenograft model also demonstrated that interference of PLAGL2 repressed the in vivo tumor growth of DLBCL. CONCLUSION: In conclusion, PLAGL2 promoted the malignancy of DLBCL through activation of Wnt/ß-catenin pathway.

A Novel Prognostic Scoring Model for Myelodysplastic Syndrome Patients With SF3B1 Mutation.

The outcomes of myelodysplastic syndrome (MDS) patients with SF3B1 mutation, despite identified as a favorable prognostic biomarker, are variable. To comprehend the heterogeneity in clinical characteristics and outcomes, we reviewed 140 MDS patients with SF3B1 mutation in Zhejiang province of China. Seventy-three (52.1%) patients diagnosed as MDS with ring sideroblasts (MDS-RS) following the 2016 World Health Organization (WHO) classification and 118 (84.3%) patients belonged to lower risk following the revised International Prognostic Scoring System (IPSS-R). Although clonal hematopoiesis-associated mutations containing TET2, ASXL1 and DNMT3A were the most frequent co-mutant genes in these patients, RUNX1, EZH2, NF1 and KRAS/NRAS mutations had significant effects on overall survival (OS). Based on that we developed a risk scoring model as IPSS-R×0.4+RUNX1×1.1+EZH2×0.6+RAS×0.9+NF1×1.6. Patients were categorized into two subgroups: low-risk (L-R, score <= 1.4) group and high risk (H-R, score > 1.4) group. The 3-year OS for the L-R and H-R groups was 91.88% (95% CI, 83.27%-100%) and 38.14% (95% CI, 24.08%-60.40%), respectively (P<0.001). This proposed model distinctly outperformed the widely used IPSS-R. In summary, we constructed and validated a personalized prediction model of MDS patients with SF3B1 mutation that can better predict the survival of these patients.

Magnolol suppressed cell migration and invasion and induced cell apoptosis via inhibition of the NF-κB signaling pathway by upregulating microRNA-129 in multiple myeloma.

Multiple myeloma (MM) is incurable cancer in the blood system. Magnolol is an effective component against various cancers. This study tried to investigate the effect and mechanism of magnolol on MM via regulating miR-129. Human normal plasma cells (nPCs) and MM cells U266 and LP1 were used in this study, accompanied by treatment of magnolol. The miR-129 inhibitor was transfected into U266 and LP1 cells during experiments. Cell viability was detected by Cell Counting Kit-8 assay. Cell migration and invasion were tested by wound healing assay and Transwell assay. And Annexin-V-FITC/PI assay was utilized to assess cell apoptosis. miR-129, miR-1271-5p, miR-342-3p, and miR-124-3p expressions were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and western blot was adopted to evaluate Cyclin D1, matrix metalloprotein (MMP)-7, MMP-9, phosphorylation (p)-IκBα, p-p65, and p65 protein levels. In U266 and LP1 cells, with magnolol concentration increasing, cell viability, migration, and invasion rates, Cyclin D1, MMP-7, and MMP-9 expressions decreased, while cell apoptosis rose. And magnolol increased the miR-129 expression in MM cells. Besides, miR-129 inhibitor antagonized the above-mentioned effect of magnolol and partly offset the magnolol-induced decrease of p-IκBα and p-p65 expression, as well as the ratio of p-p65 to p65 in U266 and LP1 cells. Magnolol suppressed cell migration and invasion and induced cell apoptosis via inhibiting NF-κB pathway activation, by upregulating miR-129 in MM.

Aidi injection combined with CHOP chemotherapy regimen in the treatment of malignant lymphoma: A meta-analysis based on randomized controlled trials.

OBJECTIVE: The aim of this study was to evaluate the clinical efficacy of Aidi injection combined with CHOP chemotherapy regimen in the treatment of malignant lymphoma. METHODS: We made an electronic search in the database of Wanfang, CNKI, and PubMed. All the clinical studies related to Aidi injection combined with CHOP chemotherapy regimen in the treatment of malignant lymphoma were screened and reviewed. The combined objective response rate (ORR), life quality improvement, and hematological toxicity were pooled by random- or fixed-effect model according to the heterogeneity across the included study. Moreover, the publication bias was evaluated by Begg's funnel plot and Egger's line regression test. RESULTS: Eight prospective clinical trials with 513 subjects (273 in the Aidi injection plus CHOP group and 240 in the CHOP group) were included in this meta-analysis. The pooled results showed that Aidi injection combined with CHOP chemotherapy regimen can significantly improve the ORR (odds ratio [OR] =1.68, 95% confidence interval [CI]: 1.09-2.60, P < 0.05), improve the life quality (OR = 3.32, 95% CI: 1.97-5.58, P < 0.05), and decrease the risk of developing leukopenia (OR = 0.25, 95% CI: 0.17-0.39, P < 0.05) and thrombocytopenia (OR = 0.34, 95% CI: 0.22-0.53, P < 0.05). CONCLUSION: With the present evidence, Aidi injection combined with CHOP chemotherapy regimen can improve the treatment response and quality of life and decrease the risk of developing severe leukopenia or thrombocytopenia.

A Case of Primary Hepatic Lymphoma and Related Literature Review.

Objective. Primary hepatic lymphoma is a rare disease. And the clinical manifestations of this disease are nonspecific. The objective of this paper is to improve clinicians' understanding of this disease. Methods. We analyzed the clinical characteristics of a case of primary hepatic lymphoma in association with hepatitis B virus infection and reviewed the literature. Conclusion. The clinical manifestations of primary hepatic lymphoma are nonspecific. And it is easily misdiagnosed. Postoperative radiotherapy of patients with early stage was previously speculated to achieve favorable improvement. The application of targeted therapeutic drugs, chemotherapy, or combined local radiotherapy has become the first-line treatment strategy.