Effects of Flavonoids and Antibiotics Combination on Preformed Biofilms and Small RNA of Staphylococcus aureus.

Antibiotic resistance of Staphylococcus aureus has considerably increased among non-clinical or asymptomatic individuals. The formation of biofilms denies antimicrobial access to its targets present on the surface and inside the cell. The present study tested the effect of the combination of flavonoids and antibiotics over the preformed biofilms of S. aureus. The eradication of the preformed biofilms was analyzed using the crystal violet method. It has shown that 2500 µg mL-1 Rutin and 100 µg mL-1 Erythromycin (MIC Concentration) combination efficiently reduced the growth of the cells, which were adhered to the surfaces forming the biofilms. Fluorescence microscopic analysis indicated that the Rutin and Erythromycin (MIC value) combinations could eradicate the preformed biofilm cells more efficiently than other combinations. We found that the flavonoids and antibiotics with MIC concentration show a significant effect over the preformed biofilms cells of S. aureus. In addition, the semi-quantitative real-time PCR analysis for the sRNAs under the treatment of Rutin and Erythromycin combinations showed that few small RNAs expression (SprF, SprG, ArtR, Teg49, Teg41, and RNAIII) are getting downregulated upon the treatment; but again recovers with the incubation time interval increases. Combinations have a significant effect on Teg49 where there is a very faint intensity of the band, but for other small RNAs, there is an irregular pattern on the gel image. It has been concluded that at the initial period of incubation, the combinations have an effect on all the sRNAs but once the incubation increases, the effects have been slowly decreasing. It has been concluded that the combination has been able to reduce the doubling time of S. aureus upon treatment. Whereas, the small RNAs used in the study can be further evaluated for expression profiling through qRT-PCT.

Lipid ROS- and Iron-Dependent Ferroptotic Cell Death in Unicellular Algae Chlamydomonas reinhardtii.

The phenomenon of heat stress leading to ferroptosis-like cell death has recently been observed in bacteria as well as plant cells. Despite recent findings, the evidence of ferroptosis, an iron-dependent cell death remains unknown in microalgae. The present study aimed to investigate if heat shock could induce reactive oxygen species (ROS) and iron-dependent ferroptotic cell death in Chlamydomonas reinhardtii in comparison with RSL3-induced ferroptosis. After RSL3 and heat shock (50 °C) treatments with or without inhibitors, Chlamydomonas cells were evaluated for cell viability and the induction of ferroptotic biomarkers. Both the heat shock and RSL3 treatment were found to trigger ferroptotic cell death, with hallmarks of glutathione-ascorbic acid depletion, GPX5 downregulation, mitochondrial dysfunction, an increase in cytosolic calcium, ROS production, lipid peroxidation, and intracellular iron accumulation via heme oxygenase-1 activation (HO-1). Interestingly, the cells preincubated with ferroptosis inhibitors (ferrostatin-1 and ciclopirox) significantly reduced RSL3- and heat-induced cell death by preventing the accumulation of Fe2+ and lipid ROS. These findings reveal that ferroptotic cell death affects the iron homeostasis and lipid peroxidation metabolism of Chlamydomonas, indicating that cell death pathways are evolutionarily conserved among eukaryotes.

Fluro-Protein C-Phycocyanin Docked Silver Nanocomposite Accelerates Cell Migration through NFĸB Signaling Pathway.

Currently, there is a great demand for the development of nanomedicine aided wound tissue regeneration via silver doped nanoceuticals. Unfortunately, very little research is being carried out on antioxidants-doped silver nanometals and their interaction on the signaling axis during the bio-interface mechanism. In this study, c-phycocyanin primed silver nano hybrids (AgcPCNP) were prepared and analyzed for properties such as cytotoxicity, metal decay, nanoconjugate stability, size expansion, and antioxidant features. Fluctuations in the expression of marker genes during cell migration phenomena in in vitro wound healing scenarios were also validated. Studies revealed that physiologically relevant ionic solutions did not exhibit any adverse effects on the nanoconjugate stability. However, acidic, alkali, and ethanol solutions completely denatured the AgcPCNP conjugates. Signal transduction RT2PCR array demonstrated that genes associated with NFĸB- and PI3K-pathways were significantly (p < 0.5%) altered between AgcPCNP and AgNP groups. Specific inhibitors of NFĸB (Nfi) and PI3K (LY294002) pathways confirmed the involvement of NFĸB signaling axes. In vitro wound healing assay demonstrated that NFĸB pathway plays a prime role in the fibroblast cell migration. In conclusion, the present investigation revealed that surface functionalized AgcPCNP accelerated the fibroblast cell migration and can be further explored for wound healing biomedical applications.

Progressive Application of Marine Biomaterials in Targeted Cancer Nanotherapeutics.

The marine microenvironment harbors many unique species of organisms that produce a plethora of compounds that help mankind cure a wide range of diseases. The diversity of products from the ocean bed serves as potentially healing materials and inert vehicles carrying the drug of interest to the target site. Several composites still lay undiscovered under the blue canopy, which can provide treatment for untreated diseases that keep haunting the earth periodically. Cancer is one such disease that has been of interest to several eminent scientists worldwide due to the heterogenic complexity involved in the disease's pathophysiology. Due to extensive globalization and environmental changes, cancer has become a lifestyle disease continuously increasing exponentially in the current decade. This ailment requires a definite remedy that treats by causing minimal damage to the body's normal cells. The application of nanotechnology in medicine has opened up new avenues of research in targeted therapeutics due to their highly malleable characteristics. Marine waters contain an immense ionic environment that succors the production of distinct nanomaterials with exceptional character, yielding highly flexible molecules to modify, thus facilitating the engineering of targeted biomolecules. This review provides a short insight into an array of marine biomolecules that can be probed into cancer nanotherapeutics sparing healthy cells.

Mapping Research on miRNAs in Cancer: A Global Data Analysis and Bibliometric Profiling Analysis.

miRNAs biomarkers are emerging as an essential part of clinical oncology. Their oncogenic and tumour suppressor properties playing a role in malignancy has generated interest in their potential for use in disease prognosis. While several studies on miRNA have been carried out across the globe, evaluating the clinical implications of miRNAs in cancer diagnosis and prognosis research has currently not been attempted. A study delineating the area of miRNA research, including the topics presently being focused on, the seminal papers in this field, and the direction of research interest, does not exist. This study aims to conduct a large-scale, global data analysis and bibliometric profiling analysis of studies to evaluate the research output of clinical implications of miRNAs in cancer diagnosis and prognosis listed in the SCOPUS database. A systematic search strategy was followed to identify and extract all relevant studies, subsequently analysed to generate a bibliometric map. SPSS software (version 27) was used to calculate bibliometric indicators or parameters for analysis, such as year and country of affiliation with leading authors, journals, and institutions. It is also used to analyse annual research outputs, including total citations and the number of times it has been cited with productive nations and H-index. The number of global research articles retrieved for miRNA-Cancer research over the study period 2003 to 2019 was 18,636. Between 2012 and 2019, the growth rate of global publications is six times (n = 15,959; 90.71 percent articles) that of 2003 to 2011. (2704; 9.29 per cent articles). China published the most publications in the field of miRNA in cancer (n = 7782; 41%), while the United States had the most citations (n = 327,538; 48%) during the time span. Of these journals, Oncotarget has the highest percentage of article publications. The journal Cancer Research had the most citations (n = 41,876), with 6.20 per cent (n = 41,876). This study revealed a wide variety of journals in which miRNA-Cancer research are published; these bibliometric parameters exhibit crucial clinical information on performance assessment of research productivity and quality of research output. Therefore, this study provides a helpful reference for clinical oncologists, cancer scientists, policy decision-makers and clinical data researchers.

A Clinical Update on the Prognostic Effect of microRNA Biomarkers for Survival Outcome in Nasopharyngeal Carcinoma: A Systematic Review and Meta-Analysis.

Background: Nasopharyngeal carcinoma (NPC), a relatively uncommon malignancy in the Western world, is highly prevalent in Southeast Asia where the treatment outcomes are poor. Despite recent improvements in diagnosis and treatment locoregional control, distant metastasis and chemoresistance continue to be a significant cause of mortality. Identification of a reliable and comprehensive prognostic biomarker is highly desirable. The potential relevance of microRNAs (miRNAs) as prognostic markers in NPC is assessed in this systematic review and meta-analysis. Methods: A systematic review was performed using the PubMed and Science Direct databases. The search was limited to search results between 2018 and 2020 with the keywords and search strings developed as per the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. The recovered articles were carefully screened based on the selection criteria. In the meta-analysis study, high and low expression levels of miRNAs were measured using the hazard ratio (HR) and 95 percent confidence interval (CI) for patients' survival outcomes. Egger's bias indicator test and funnel plot symmetry were used to assess the risk of bias. Results: Amongst the 25 studies, 13 fulfilled the conditions of inclusion in this meta-analysis. The researchers further delved into the 21 miRNA expression levels from 3015 NPC patients to ascertain a link between miRNA's predictive role and survival outcomes. The majority of the articles retrieved during this study were from China, with two studies from Canada and Malaysia. The overall pooled effect size estimation (HR) for dysregulated miRNAs was 1.590 (95% CI: 1.253-2.017), displaying that miRNA marker expression increased the risk of mortality in NPC patients by 59%. Conclusions: This meta-analysis is novel and looks at the prognostic significance of miRNAs as biomarkers in NPC patients using a continuous version pooled meta-analysis. Although our findings are ambiguous, they do show that greater miRNA expression in NPC may be associated with a lower overall survival rate. To acquire clear conclusions, more prospective studies with large cohorts are required to determine the clinical utility of miRNAs as prognostic biomarkers.

Prognostic Utility of Platelet-Lymphocyte Ratio, Neutrophil-Lymphocyte Ratio and Monocyte-Lymphocyte Ratio in Head and Neck Cancers: A Detailed PRISMA Compliant Systematic Review and Meta-Analysis.

Inflammation plays a major role in cancer development and progression and has the potential to be used as a prognostic marker in cancer. Previous studies have attempted to evaluate Platelet-to-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR) or monocyte-lymphocyte ratio (MLR) as indicators of inflammation/prognostic markers in cancer, but there is no common consensus on their application in clinical practice. The aim of this systematic review and meta-analysis is to (a) assess the prognostic efficacy of all three prognostic markers in comparison to each other and (b) investigate the prognostic potential of these three markers in HNC. The study followed PRISMA guidelines, with the literature being collated from multiple bibliographic databases. Preliminary and secondary screening were carried out using stringent inclusion/exclusion criteria. Meta-analysis was carried out on selected studies using CMA software and HR as the pooled effect size metric. A total of 49 studies were included in the study. The pooled HR values of PLR, NLR and MLR indicated that they were significantly correlated with poorer OS. The pooled effect estimates for PLR, NLR and MLR were 1.461 (95% CI 1.329-1.674), 1.639 (95% CI 1.429-1.880) and 1.002 (95% CI 0.720-1.396), respectively. Significant between-study heterogeneity was observed in the meta-analysis of all three. The results of this study suggest that PLR, NLR and MLR ratios can be powerful prognostic markers in head and neck cancers that can guide treatment. Further evidence from large-scale clinical studies on patient cohorts are required before they can be incorporated as a part of the clinical method. PROSPERO Registration ID: CRD42019121008.