Characterization of the novel broad-spectrum lytic phage Phage_Pae01 and its antibiofilm efficacy against Pseudomonas aeruginosa.

Introduction: Pseudomonas aeruginosa is present throughout nature and is a common opportunistic pathogen in the human body. Carbapenem antibiotics are typically utilized as a last resort in the clinical treatment of multidrug-resistant infections caused by P. aeruginosa. The increase in carbapenem-resistant P. aeruginosa poses an immense challenge for the treatment of these infections. Bacteriophages have the potential to be used as antimicrobial agents for treating antibiotic-resistant bacteria. Methods and Results: In this study, a new virulent P. aeruginosa phage, Phage_Pae01, was isolated from hospital sewage and shown to have broad-spectrum antibacterial activity against clinical P. aeruginosa isolates (83.6%). These clinical strains included multidrug-resistant P. aeruginosa and carbapenem-resistant P. aeruginosa. Transmission electron microscopy revealed that the phage possessed an icosahedral head of approximately 80 nm and a long tail about 110 m, indicating that it belongs to the Myoviridae family of the order Caudovirales. Biological characteristic analysis revealed that Phage_Pae01 could maintain stable activity in the temperature range of 4~ 60°C and pH range of 4 ~ 10. According to the in vitro lysis kinetics of the phage, Phage_Pae01 demonstrated strong antibacterial activity. The optimal multiplicity of infection was 0.01. The genome of Phage_Pae01 has a total length of 93,182 bp and contains 176 open reading frames (ORFs). The phage genome does not contain genes related to virulence or antibiotic resistance. In addition, Phage_Pae01 effectively prevented the formation of biofilms and eliminated established biofilms. When Phage_Pae01 was combined with gentamicin, it significantly disrupted established P. aeruginosa biofilms. Conclusion: We identified a novel P. aeruginosa phage and demonstrated its effective antimicrobial properties against P. aeruginosa in both the floating and biofilm states. These findings offer a promising approach for the treatment of drug-resistant bacterial infections in clinical settings.

The Postoperative Platelet to Creatinine Ratio as A Prognostic Index of In-Hospital Mortality in Patients with Acute Type A Aortic Dissection.

BACKGROUND: The purpose of the investigation was to assess the value of post-operation platelet to creatinine ratio (PCR) in predicting in-hospital mortality among patients with acute type A aortic dissection (TAAAD). METHODS: A retrospective study was carried out from January 2017 to December 2019. The best cutoff value of post-operation PCR was assessed by receiver operating characteristic (ROC) curve. Patients were divided into survivors and nonsurvivors. Univariate and multivariate logistic analyses were carried out to identify independent risk factors influencing in-hospital mortality. RESULTS: A total of 171 patients were included in this investigation, with an in-hospital mortality rate of 18.1%. The optimal cut-off value of post-operation PCR was 0.7242 (area under the ROC curve (AUC): 0.798, 95% confidence interval (CI) 0.730-0.856, p < 0.001), and the sensitivity and specificity were 74.2% and 74.3%. The levels of post-operation PCR were lower in nonsurvivors than in survivors (0.56 ± 0.33 vs. 1.50 ± 1.36, p < 0.001). Multivariate logistic regression analysis displayed that post-operation PCR was positively related to in-hospital survivors when confounding factors were adjusted (HR = 8.850, 95% CI = 2.611-30.303, p < 0.001). CONCLUSIONS: Post-operative PCR is a readily accessible and cost-effective biomarker that is independently associated with in-hospital mortality in TAAAD patients. Furthermore, it exhibits superior performance in predicting patient outcomes following surgery.

Elevated neutrophil - to - monocyte ratio as a prognostic marker for poor outcomes in neonatal sepsis.

Objectives: Neonatal sepsis is one of the leading causes of neonatal death. The aim of this study was to evaluate the value of neutrophil - to - monocyte ratio (NMR) in predicting mortality in neonatal sepsis. Methods: In this present retrospective study, a total of 134 neonates with sepsis were included. Baseline laboratory parameters were collected. The best cutoff value of NMR was determined by receiver operating characteristic (ROC) curve. Univariate and multivariate analysis were carried out to survey the predict value of NMR. Results: The results showed that NMR in non-survival group was significantly higher than that in survival group. Results from multivariate analysis showed that high NMR was an independent risk factor for neonatal sepsis (Hazard ratio (HR): 7.519, p = 0.001). ROC displayed that the area under curve (AUC) of NMR was 0.740, sensitivity and specificity of NMR were 80% and 65.8% when 7.65 was selected. Conclusions: NMR could be a promising prognostic factor for neonatal sepsis.

Evaluation of the Efficacy of Stem Cell Therapy in Ovariectomized Osteoporotic Rats Based on Micro-CT and Dual-Energy X-Ray Absorptiometry: A Systematic Review and Meta-Analysis.

OBJECTIVE: Osteoporosis is an abnormal bone metabolism disease characterized by microstructural degeneration of bone tissue and reduction in bone mass, resulting in increased brittleness of bone tissue and susceptibility to fracture. Due to the tissue regenerative potential of stem cell transplantation, it is now used in the treatment of various disease models such as osteoporosis. The purpose of this work is to carry out a systematic review and meta-analysis of the efficacy of stem cell therapy in ovariectomized (OVX) osteoporotic rats. METHODS: PubMed, Cochrane Library, ScienceDirect, Embase, CNKI, and Wanfang Databases were used to search for articles that met the inclusion criteria. Two researchers independently screened the articles that met the inclusion criteria. RevMan 5.3 and STATA 16.0 were used for data analysis. This meta-analysis was registered at INPLASY with reference number ID: INPLASY202150017. RESULTS: Thirteen eligible studies were selected, including 405 rats. The sources of stem cells are divided into four main categories: bone marrow mesenchymal stem cells (BMSCs), adipose-derived stem cells (ADSCs), amniotic membrane mesenchymal stem cells (AM-MSCs), and human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs). Compared with the OVX group, both stem cell transplantation groups had higher bone mineral density (BMD) (BMSCs: SMD = 2.01, 95% CI: [1.38, 2.63], P < 0.001, I 2 = 76.6%; ADSCs: SMD = 2.24, 95% CI: [0.79, 3.69], P = 0.003, I 2 = 86.7%) and bone volume/total volume (BV/TV) (hUCB-MSCs: SMD = 1.71, 95% CI: [0.97, 2.44], P < 0.001, I 2 = 0%; ADSCs: SMD = 2.16, 95% CI: [0.27, 4.04], P = 0.025, I 2 = 82.6%). In the BMSC treatment groups, the trabecular numbers (Tb.N) (SMD = 4.28, 95% CI: [0.91, 7.64], P = 0.013, I 2 = 94.9%) were significantly higher, whereas the results for trabecular thickness (Tb.Th) (SMD = 2.7, 95% CI: [-0.34, 5.73], P = 0.081, I 2 = 95.4%) and trabecular spacing (Tb.Sp) (SMD = -3.08, 95% CI: [-6.55, 0.38], P = 0.081, I 2 = 96.3%) were not statistically significant compared to those of the OVX group. The stem cell transplantation group had a low BMD, BV/TV, and Tb.N compared to the sham operation group. CONCLUSION: Stem cell therapy may increase bone strength, bone volume, and the number of trabeculae in OVX osteoporotic rats. The results of this meta-analysis showed the potential therapeutic effect of stem cell transplantation in OVX osteoporotic rats, bringing new therapeutic ideas and directions to the clinical treatment of osteoporosis. Due to the limited number and quality of studies related to some outcomes, more high-quality RCTs are still needed in the future to complement the existing findings.

GATA1/SP1 and miR-874 mediate enterovirus-71-induced apoptosis in a granzyme-B-dependent manner in Jurkat cells.

Enterovirus 71 (EV71)-induced T lymphocyte apoptosis plays an important role in hand, foot, and mouth disease (HFMD), and granzyme B (GZMB) has been shown to be critical for this process. However, the mechanisms underlying GZMB-mediated apoptosis of T lymphocytes remain unknown. In this study, we investigated whether transcription factors and microRNAs (miRNAs) are involved in GZMB-mediated apoptosis of T lymphocytes in response to EV71 infection. Our findings indicated that EV71 infection significantly induced apoptosis in Jurkat cells, a human T lymphocytes cell line, as revealed in flow cytometric analysis. Furthermore, EV71 increased the expression of pro-apoptosis Bcl-2-associated X (Bax) and cleaved caspase 3 but decreased the expression of anti-apoptosis B-cell lymphoma protein 2 (Bcl2). GZMB knockdown decreased cell apoptosis and prevented EV71-induced changes in the expression of Bax, cleaved caspase 3, and Bcl2 in Jurkat cells, highlighting the role of GZMB as a key factor in EV71-induced apoptosis. Our study also indicated that overexpression of the transcription factors GATA binding factor 1 (GATA1) and specificity protein 1 (SP1) significantly increased luciferase activity when this gene was inserted in the GZMB 3' untranslated region (3'UTR). GATA1/SP1 overexpression induced cell apoptosis, increased the expression of Bax and cleaved caspase 3, and decreased the expression of Bcl2. Finally, our results suggested that miR-874 plays an essential role in GZMB-mediated cell apoptosis, since an miR-874 mimic decreases the expression of GZMB by targeting its 3'UTR. Collectively, these data indicated that GATA1/SP1 and miR-874 mediate EV71-induced apoptosis in a granzyme B-dependent manner. This signaling pathway may provide a new pharmacological target for the prevention and treatment of HFMD.

Activation of GPR120 promotes the metastasis of breast cancer through the PI3K/Akt/NF-κB signaling pathway.

G-protein-coupled receptor 120 (GPR120) plays an important role in regulating lipid and glucose metabolism as a long-chain unsaturated fatty acid receptor. However, it has been widely accepted that omega-3 polyunsaturated fatty acids are not dependent on the activation of GPR120 to exert anti-tumor activity. Therefore, the role of GPR120 in tumor development has not yet been elucidated. Here we show that activation of GPR120 promotes angiogenesis and metastasis in human breast cancer. We show that activation of GPR120 in human breast cancer cells can promote vascular endothelial growth factor, interleukin-8 secretion, cell migration, and epithelial mesenchymal transition. Similarly, phosphatidylinositide 3-kinases/RAC-alpha serine/threonine-protein kinase/nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway is involved in GPR120 activation-induced cell migration and epithelial mesenchymal transition in breast cancer cells. In conclusion, our findings indicate that GPR120 acts as a cancer-promoting receptor in the development of breast cancer. Therefore, GPR120 is expected to be a potential new target for cancer therapy.

IFN-γ Induces Gastric Cancer Cell Proliferation and Metastasis Through Upregulation of Integrin ß3-Mediated NF-κB Signaling.

Interferon γ (IFN-γ), a multifunctional cytokine, was upregulated in the resected gastric cancer tissue. However, whether IFN-γ is involved in the regulation of gastric cancer has not been well elucidated. Herein, we aimed to investigate the effects and mechanism of IFN-γ on gastric cancer. In this study, we found a vital role of IFN-γ in enhancing proliferation, inhibiting apoptosis, and promoting cell migration and invasion in gastric cancer cells SGC-7901 and MGC-803. Additionally, IFN-γ activated nuclear factor κB (NF-κB) signaling pathway by upregulating the phosphorylation expression of p65 and IκBα, and induced the expression of integrin ß3 in vitro. Therefore, to further investigate the relationship between IFN-γ and integrin ß3, SGC-7901 cells were transfected with integrin ß3 siRNA. And then cells expressed lower cell viability, migration, and invasion rates, while cell apoptosis was significantly enhanced. Meanwhile, expression of integrin ß3, MMP-2, MMP-9, and NF-κB, including p65 and IκBα, and the nuclear translocation of NF-κB/p65 were dramatically repressed, whereas IFN-γ significantly improved the effects. Moreover, in vivo, the experiment of xenograft model and pulmonary metastasis model also retarded in integrin ß3 siRNA group. And the expression of integrin ß3, MMP-2, MMP-9, and NF-κB was repressed. However, the treatment with IFN-γ improved tumor volume, lung/total weight, tumor nodules, and the protein expression described above compared with integrin ß3 siRNA group. Overall, the results indicated that IFN-γ induces gastric cancer cell proliferation and metastasis partially through the upregulation of integrin ß3-mediated NF-κB signaling. Hence, the inhibition of IFN-γ or integrin ß3 may be the key for the treatment of gastric cancer.