Synergistic Effects of Phage-Antibiotic Combinations against Citrobacter amalonaticus.

Non-antibiotic alternative treatments to combat the increasing number of infections caused by multidrug resistant bacteria are urgently needed. In recent years, bacteriophages have reemerged to potentially replace or complement the role of antibiotics, as bacterial viruses have the ability to inactivate pathogens. This study aimed to evaluate the synergy of phage-antibiotic combinations. A Citrobacter amalonaticus isolate was used in this study together with the phage MRM57. Eight different antibiotics with different mechanisms of action were used in combination with the phage to study the impact of the combination treatment on the minimal inhibitory concentrations. We found that antibiotic concentration dependent synergism exists, albeit at different extents, with very low numbers of phages. This demonstrates the use of phages as an adjuvant with a sublethal concentration of antibiotics as an effective therapeutic strategy.

Isolation, characterization, and efficacy of bacteriophages isolated against Citrobacter spp. an in vivo approach in a zebrafish model (Danio rerio).

Citrobacter infections are becoming an increasingly significant health problem in aquaculture in South-Eastern countries. The objective of this study was to isolate and evaluate the potential of lytic bacteriophages against Citrobacter infections. TEM analysis revealed that the isolated phages Citrophage MRM19 and Citrophage MRM57 were identified to be Siphovirus and Podovirus family of the order Caudovirales. The phage life-cycle studies showed that Citrophage MRM19 had an adsorption time of 18 ± 1 min and a latency period of 25 ± 3 min with burst size of 110 ± 20 phages/infected cell and Citrophage MRM57 had an adsorption time of 15 ± 1 min and a latency period of 25 ± 2 min with burst size of 50 ± 5 phages/infected cell. In vitro studies indicated that the bacterial load was reduced by 5 and 7 log units within 12 h by Citrophage MRM19 and Citrophage MRM57. The in vivo efficacy of the phages was studied using zebrafish (Danio rerio) as a model organism in low-scale tanks. The study unveiled that the use of phages increased the survival up to 17%, 23%, and 26% in the case of Citrophage MRM19, Citrophage MRM57, and phage cocktail treatment, respectively. Our study indicated that bacteriophages are suitable biocontrol agents against Citrobacter spp. especially in aquaculture industry.

Prognostic Significance of FOXC1 in Various Cancers: A Systematic Review and Meta-Analysis.

BACKGROUND: Forkhead box C1 (FOXC1), a member of the Forkhead box (Fox) transcription factor family, plays an essential role in lymphatic vessel formation, angiogenesis and metastasis. Observational studies examining the relationship between the protein biomarker FOXC1 and breast cancer prognosis have reported conflicting findings. This systematic review and meta-analysis evaluates the prognostic value of the FOXC1 expression in association with patient survival in breast cancer and other types of cancers in order to identify the overall prognostic effectiveness of FOXC1. METHODS: This study followed the guidelines established in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We conducted a broad search on the online bibliographic databases EMBASE, PubMed, Science Direct and Scopus, limiting search to publications from 2010 to 2018. The prognostic value was demonstrated by a random effects model meta-analysis using the hazard ratio (HR) with 95% confidence interval (CI) for overall survival (OS) in various cancer patients. The heterogeneity was measured by the I2 statistic. Publication bias and quality assessment for the selected articles was performed. Subgroup analysis was conducted based on the data available from the selected articles. RESULTS: A total of 16 studies met the predefined selection criteria established for our systematic review and meta-analysis, with multiple studies using diverse methodologies and reported on differing clinical outcomes, falling under a common banner of FOXC1 expression and survival in cancer. Overall, we observed a statistically non-significant association between FOXC1 protein expression and patients survival (HR: 1.186 and 95% CI 1.122-1.255, p = 0.000, I2 = 88.83%). CONCLUSION: In summary, FOXC1 protein expression indicated poor survival outcome in various carcinomas, especially in patients with breast cancer, suggesting it as a possible biomarker for the prognosis in multiple carcinomas. Further clinical evaluation and large-scale cohort studies are required to accurately identify its possible clinical utility.

Prognostic significance of blood inflammatory biomarkers NLR, PLR, and LMR in cancer-A protocol for systematic review and meta-analysis.

BACKGROUND: The neutrophil-lymphocyte-ratio, platelet-lymphocyte-ratio, and monocyte-lymphocyte-ratio have been explored as a simple, inexpensive, and effective method for cancer prognosis. However, there are no studies that have investigated the comparative utility of these markers, in multiple cancers. METHODS: The preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) guidelines were used to design this meta-analysis protocol. The final study will also be conducted under the PRISMA guidelines for systematic reviews and meta-analyses. The core bibliographic database search will be carried out by 2 reviewers working individually, with each conducting an initial screening based on titles and abstracts. The shortlisted articles will be selected for review and quantitative analysis, based on predefined inclusion and exclusion criteria. Study characteristics, relevant clinicopathological characteristics, and statistical data required for meta-analysis (hazard ratios [HRs] and 95% confidence intervals [CIs]) will be extracted and compiled into a MS Excel datasheet. Meta-analysis will be performed, using a random-effects model, and the results (pooled HR and 95% CI) will be presented in the form of a forest plot. Publication bias will also be assessed by use of Egger bias indicator test and funnel plot symmetry. If statistical data from included studies is insufficient, a qualitative literature review will be pursued.PROSPERO registration: PROSPERO CRD42019121008.

miRNA Predictors of Pancreatic Cancer Chemotherapeutic Response: A Systematic Review and Meta-Analysis.

BACKGROUND: pancreatic cancer (PC) has increasing incidence and mortality in developing countries, and drug resistance is a significant hindrance to the efficacy of successful treatment. The objective of this systematic review and meta-analysis was to evaluate the association between miRNAs and response to chemotherapy in pancreatic cancer patients. METHODS: the systematic review and meta-analysis was based on articles collected from a thorough search of PubMed and Science Direct databases for publications spanning from January 2008 to December 2018. The articles were screened via a set of inclusion and exclusion criteria based on the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. Data was extracted, collated and tabulated in MS Excel for further synthesis. Hazard ratio (HR) was selected as the effect size metric to be pooled across studies for the meta-analysis, with the random effects model being applied. Subgroup analysis was also conducted, and the presence of publication bias in the selected studies was assessed. Publication bias of the included studies was quantified. FINDINGS: of the 169 articles screened, 43 studies were included in our systematic review and 13 articles were included in the meta-analysis. Gemcitabine was observed to be the principal drug used in a majority of the studies. A total of 48 miRNAs have been studied, and 18 were observed to have possible contributions to chemoresistance, while 15 were observed to have possible contributions to chemosensitivity. 41 drug-related genetic pathways have been identified, through which the highlighted miRNA may be affecting chemosensitivity/resistance. The pooled HR value for overall survival was 1.603; (95% Confidence Interval (CI) 1.2-2.143; p-value: 0.01), with the subgroup analysis for miR-21 showing HR for resistance of 2.061; 95% CI 1.195-3.556; p-value: 0.09. INTERPRETATION: our results highlight multiple miRNAs that have possible associations with modulation of chemotherapy response in pancreatic cancer patients. Further studies are needed to discover the molecular mechanisms underlying these associations before they can be suggested for use as biomarkers of response to chemotherapeutic interventions in pancreatic cancer.

Validation of miRNA prognostic significance in stage II colorectal cancer: A protocol for systematic review and meta-analysis of observational clinical studies.

BACKGROUND: Advances in early detection and treatment of colorectal cancer (CRC) has seen marked improvements in recent years. However, it is still the third leading cause of cancer-related deaths worldwide. Although there are studies reporting the significance of miRNAs in stage II colorectal cancer, there is no known comprehensive study utilising collective data from multiple published studies. Thus, this study will focus on performing a systematic review and meta-analysis using published data to identify and underline multiple miRNA targets, with regard to disease prognosis in stage II CRC patients. METHODS: The systematic review will be reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, 2015 statement. The required articles will be obtained via a search of bibliographical databases such as Cochrane Library, EMBASE, MEDLINE, PubMed, and Web of Science. A set of keywords in multiple permutations will be used for the search. The reference lists of included studies will also be manually searched to further increase the robustness of the search results. The systematic review will primarily be done via a literary synthesis. RESULTS: Quantitative data synthesis will be based on estimated effect across the studies with forest plots generated to observe pooled outcome measures. A fixed or random-effect model of meta-analysis will be used depending upon the heterogeneity observed between studies. Subgroup analysis will be carried out depending on the availability of sufficient clinical data. CONCLUSION: Based on the systematic review and meta-analysis results of this study, the possible miRNAs could be predicted toward the prognosis of stage II colorectal cancer, and specific miRNAs may perhaps be considered as a biomarker and therapeutic target for this malignancy.

Prognostic miRNA classifiers in t cell acute lymphoblastic leukemia: Study protocol for a systematic review and meta-analysis of observational clinical studies.

BACKGROUND: The prognostic value of microRNA (miRNA) expression in T-cell acute lymphoblastic leukemia (T-ALL) has generated significant research interest in recent years. However, most diagnostic and prognostic studies with regards to miRNA expression have been focused on combined B cell and T cell lymphoblastic leukemia. There are very few studies reporting the prognostic effects of miRNA expression on T-ALL. Therefore, a pioneer systematic review and meta-analysis was proposed to explore the possibilities of miRNAs as viable prognostic markers in T-ALL. This study is intended to be useful as a guideline for future research into drug evaluation and targeting miRNA as a biomarker for the treatment and prognosis of T-ALL. METHODS: The systematic review will be reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. The study search will be conducted by using Cochrane, EMBASE, Medline, Science Direct, and SCOPUS bibliographic databases. The reference lists of included studies will be manually searched to further bolster the search results. A combination of keywords will be used to search the databases. DISCUSSION: To explore the effect of miRNA on prognosis, forest plots will be generated to assess pooled HR and 95% CI. Upregulation, downregulation, and deregulation of specific miRNAs will be individually noted and used to extrapolate patient prognosis when associated with risk factors involved in T-ALL. Subgroup analysis will be carried out to analyze the effect of deregulation of miRNA expression on patient prognosis. A fixed or random-effects model of meta-analysis will be used depending upon between-study heterogeneity. This systematic review and meta-analysis will identify and synthesize evidence to determine the prognosis of miRNA in T-ALL and suggest the possible miRNA from meta-analysis results to predict as a biomarker for further detection and treatment of T-ALL.

Current Evidence on miRNAs as Potential Theranostic Markers for Detecting Chemoresistance in Colorectal Cancer: A Systematic Review and Meta-Analysis of Preclinical and Clinical Studies.

BACKGROUND: Findings from observational clinical studies examining the relationship between biomarker expression and theranosis in colorectal cancer (CRC) have been conflicting. OBJECTIVE: We conducted this systematic review and meta-analysis to summarise the existing evidence to demonstrate the involvement of microRNAs (miRNAs) in chemoresistance and sensitivity in CRC through drug genetic pathways. METHODS: Using PRISMA guidelines, we systematically searched PubMed and Science Direct for relevant studies that took place between 2012 and 2017. A random-effects model of meta-analysis was applied to evaluate the pooled effect size of hazard ratios (HRs) across the included studies. Cochran's Q test and the I2 statistic were used to detect heterogeneity. A funnel plot was used to assess potential publication bias. RESULTS: Of the 4700 studies found, 39 studies comprising 2822 patients with CRC met the inclusion criteria. The included studies used one or a combination of 14 chemotherapy drugs, including 5-fluorouracil and oxaliplatin. Of the 60 miRNAs, 28 were associated with chemosensitivity, 20 with chemoresistance, and one with differential expression and radiosensitivity; ten miRNAs were not associated with any impact on chemotherapy. The results outline the importance of 34 drug-regulatory pathways of chemoresistance and sensitivity in CRC. The mean effect size was 0.689 (95% confidence interval 0.428-1.110), indicating that the expression of miRNAs decreased the likelihood of death by about 32%. CONCLUSION: Studies have consistently shown that multiple miRNAs could act as clinical predictors of chemoresistance and sensitivity. An inclusion of supplementary miRNA estimation in CRC routine practice needs to be considered to evaluate the efficacy of chemotherapy after confirming our findings with large-scale prospective cohort studies. PROSPERO REGISTRATION NUMBER: CRD42017082196.

Effect of various bacteriological media on the plaque morphology of Staphylococcus and Vibrio phages.

The influence of media composition on the life cycle of bacteriophages to exhibit diverse plaque morphology on various bacteriological media was investigated by a double agar overlay method. Both Staphylococcus aureus phage and Vibrio parahaemolyticus phage showed altered plaque morphology from small to large and from clear to turbid, in different culture media used for the double agar overlay method.

Systematic Review and Meta-analysis of the Prognostic Significance of miRNAs in Melanoma Patients.

BACKGROUND: Melanoma is the most aggressive and deadly form of skin cancer. The molecular variability involving microRNA (miRNA) expression plays a significant role in melanogenesis, which leads to poor prognostic effects in melanoma. Since there is a scarcity of comprehensive data on the prognostic role of miRNAs in melanoma patients, this study focuses on filling this knowledge gap through a systematic review and meta-analysis. METHODS: The included studies were extracted from several bibliographic databases between 2012 and 2018 using multiple keywords according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The hazard ratios (HRs) and 95% confidence intervals (CIs) for different survival endpoints were compared to the high and low expression levels of miRNAs. The mean effect size of HR values was estimated using a random-effects model of meta-analysis. Inverted funnel plot symmetry was used to assess publication bias. Subgroup analysis was carried out individually for multiple miRNAs across different studies. RESULTS: A total of 24 studies across eight countries were included, of which 16 studies were eligible for meta-analysis. Twenty-five miRNA expression levels were studied from 2669 melanoma patients to estimate the association between the prognostic role of miRNAs and survival outcome in these 16 studies. The overall pooled effect size (HR) for up- and downregulated miRNAs was 1.043 (95% CI 0.921-1.181; p = 0.506), indicating that the miRNA expression increased the likelihood of death in melanoma patients by 4.3%. Subgroup analysis for miRNA10b, miRNA16 and miRNA21 showed a poor prognosis. The quality assessment revealed that 16 studies were good quality and eight studies were of fair quality. CONCLUSION: This is one of the first pooled meta-analysis studies on the role of miRNAs in the prognosis of melanoma. Our findings are inconclusive but suggest that miRNA expression could predict poor survival in melanoma patients. Therefore, miRNA expression could act as promising prognostic marker for melanoma.

Letter to the editor: is HIF-1α a viable prognostic indicator in OSCC? A critical review of a meta-analysis study.

The study performed by Zhou et al. (World J Surg Oncol 15:104, 2017) titled "Clinical and prognostic significance of HIF-1α overexpression in oral squamous cell carcinoma: a meta-analysis" attempts to highlight hypoxia-inducible factor-1 alpha as a possible prognostic marker in oral squamous cell carcinoma (OSCC). We would like to underline a few points which may affect such a conclusion. The correlations between HIF-1α expression and tumour size as well as tumour stage are debatable. Further, the subgroup analysis incorporating Australia and Europe into a single subgroup limits the viability of the prognostic analysis of HIF-1α. We also suggest future studies in the same research area to analyse head and neck squamous cell carcinoma instead of OSCC, to ameliorate the limitations encountered by Zhou et al., due to the scarcity of relevant clinical data and a low number of studies about OSCC.

Toxicity, uptake, and accumulation of nano and bulk cerium oxide particles in Artemia salina.

Although the toxicological impact of metal oxide nanoparticles has been studied for the last few decades on aquatic organisms, the exact mechanism of action is still unclear. The fate, behavior, and biological activity of nanoparticles are dependent on physicochemical factors like size, shape, surface area, and stability in the medium. This study deals with the effect of nano and bulk CeO2 particles on marine microcrustacean, Artemia salina. The primary size was found to be 15 ± 3.5 and 582 ± 50 nm for nano and bulk CeO2 (TEM), respectively. The colloidal stability and sedimentation assays showed rapid aggregation of bulk particles in seawater. Both the sizes of CeO2 particles inhibited the hatching rate of brine shrimp cyst. Nano CeO2 was found to be more toxic to A. salina (48 h LC50 38.0 mg/L) when compared to bulk CeO2 (48 h LC50 92.2 mg/L). Nano CeO2-treated A. salina showed higher oxidative stress (ROS) than those treated with the bulk form. The reduction in the antioxidant activity indicated an increase in oxidative stress in the cells. Higher acetylcholinesterase activity (AChE) was observed upon exposure to nano and bulk CeO2 particles. The uptake and accumulation of CeO2 particles were increased with respect to the concentration and particle size. Thus, the above results revealed that nano CeO2 was more lethal to A. salina as compared to bulk particles.