Antibacterial Activity of Iranian Green and Black Tea on Streptococcus Mutans: An In Vitro Study

Objective: Dental caries is a common infectious disease.Streptococcus mutans is the prevalent decay microorganism. The anti Streptococcus mutans activity of non fermented and semi-fermented tea has been shown. The aim of this study was to determine the anti Streptococcus mutans activity of Iranian green and black tea (non fermented and fermented type).Materials and Methods: The study was experimental. The aerial parts of wild-growing Camellia sinensis were collected from Lahijan province. The methanolic extract of green and black tea were examined on Streptococcus mutans (ATCC3566). Five different concentrations (50mg/ml, 100mg/ml, 200mg/ml, 300mg/ml and 400 mg/ml) of tea extracts were tested using the well assay method. The agar dilution method recommended by the NCCLS standards (National Committee for Clinical Laboratory Standards) was used. Theminimum inhibitory concentration (MIC) was determined as the lowest concentration of extract inhibiting visible growth of the organism on the agar media plate. Minimum bactericidal concentration (MBC) was detected from MIC.Results: The Iranian green and black tea had an antibacterial effect on 100 to 400 mg/ml concentrations. The minimum inhibitory concentration of green and black tea was 150 and 50 mg/ml, respectively. The mean diameter of inhibition zone were 9.5 mm and 10.9 mm for methanolic extract of green and black tea, respectively.Conclusion: Both Iranian non fermented (green tea) and fermented (black tea) have anti Streptococcus mutans activity in vitro. The anti Streptococcus mutans activity of black tea appears on a lower concentration than green tea

Activation of the Aryl Hydrocarbon Receptor Interferes with Early Embryonic Development.

The transcriptional program of early embryonic development is tightly regulated by a set of well-defined transcription factors that suppress premature expression of differentiation genes and sustain the pluripotent identity. It is generally accepted that this program can be perturbed by environmental factors such as chemical pollutants; however, the precise molecular mechanisms remain unknown. The aryl hydrocarbon receptor (AHR) is a widely expressed nuclear receptor that senses environmental stimuli and modulates target gene expression. Here, we have investigated the AHR interactome in embryonic stem cells by mass spectrometry and show that ectopic activation of AHR during early differentiation disrupts the differentiation program via the chromatin remodeling complex NuRD (nucleosome remodeling and deacetylation). The activated AHR/NuRD complex altered the expression of differentiation-specific genes that control the first two developmental decisions without affecting the pluripotency program. These findings identify a mechanism that allows environmental stimuli to disrupt embryonic development through AHR signaling

A machine learning model for predicting favorable outcome in severe traumatic brain injury patients after 6 months

Background: Traumatic brain injury (TBI), which occurs commonly worldwide, is among the more costly of health and socioeconomic problems. Accurate prediction of favorable outcomes in severe TBI patients could assist with optimizing treatment procedures, predicting clinical outcomes, and result in substantial economic savings. Methods: In this study, we examined the capability of a machine learning-based model in predicting �favorable� or �unfavorable� outcomes after 6 months in severe TBI patients using only parameters measured on admission. Three models were developed using logistic regression, random forest, and support vector machines trained on parameters recorded from 2,381 severe TBI patients admitted to the neuro-intensive care unit of Rajaee (Emtiaz) Hospital (Shiraz, Iran) between 2015 and 2017. Model performance was evaluated using three indices: sensitivity, specificity, and accuracy. A ten-fold cross-validation method was used to estimate these indices. Results: Overall, the developed models showed excellent performance with the area under the curve around 0.81, sensitivity and specificity of around 0.78. The top-three factors important in predicting 6-month post-trauma survival status in TBI patients are �Glasgow coma scale motor response,� �pupillary reactivity,� and �age.� Conclusions: Machine learning techniques might be used to predict the 6-month outcome in TBI patients using only the parameters measured on admission when the machine learning is trained using a large data set. © 2022 Korean Society of Critical Care Medicine. All right reserved

The BCL-2 pathway preserves mammalian genome integrity by eliminating recombination-defective oocytes

DNA double-strand breaks (DSBs) are toxic to mammalian cells. However, during meiosis, more than 200 DSBs are generated deliberately, to ensure reciprocal recombination and orderly segregation of homologous chromosomes. If left unrepaired, meiotic DSBs can cause aneuploidy in gametes and compromise viability in offspring. Oocytes in which DSBs persist are therefore eliminated by the DNA-damage checkpoint. Here we show that the DNA-damage checkpoint eliminates oocytes via the pro-apoptotic BCL-2 pathway members Puma, Noxa and Bax. Deletion of these factors prevents oocyte elimination in recombination-repair mutants, even when the abundance of unresolved DSBs is high. Remarkably, surviving oocytes can extrude a polar body and be fertilised, despite chaotic chromosome segregation at the first meiotic division. Our findings raise the possibility that allelic variants of the BCL-2 pathway could influence the risk of embryonic aneuploidy

Dynamic proteomic profiling of extra-embryonic endoderm differentiation in mouse embryonic stem cells

During mammalian pre-implantation development, the cells of the blastocyst’s inner cell mass differentiate into the epiblast and primitive endoderm lineages, which give rise to the fetus and extra-embryonic tissues, respectively. Extra-embryonic endoderm differentiation can be modeled in vitro by induced expression of GATA transcription factors in mouse embryonic stem cells. Here we use this GATA-inducible system to quantitatively monitor the dynamics of global proteomic changes during the early stages of this differentiation event and also investigate the fully differentiated phenotype, as represented by embryo-derived extra-embryonic endoderm (XEN) cells. Using mass spectrometry-based quantitative proteomic profiling with multivariate data analysis tools, we reproducibly quantified 2,336 proteins across three biological replicates and have identified clusters of proteins characterized by distinct, dynamic temporal abundance profiles. We first used this approach to highlight novel marker candidates of the pluripotent state and extra-embryonic endoderm differentiation. Through functional annotation enrichment analysis, we have shown that the downregulation of chromatin-modifying enzymes, the re-organization of membrane trafficking machinery and the breakdown of cell-cell adhesion are successive steps of the extra-embryonic differentiation process. Thus, applying a range of sophisticated clustering approaches to a time-resolved proteomic dataset has allowed the elucidation of complex biological processes which characterize stem cell differentiation and could establish a general paradigm for the investigation of these processes.This work was supported by the European Union 7th Framework Program (PRIME-XS project grant number 262067 to K.S.L., L.G and C.M.M), the Biotechnology and Biological Sciences Research Council (BBSRC grant number BB/L002817/1 to K.S.L and L.G.), as well as a HFSP grant (RGP0029/2010) and a European Research Council (ERC) Advanced Investigator grant to A.M.A.. C.S was supported by an EMBO long term fellowship and a Marie Curie IEF. L.T.Y.C. and K.K.N. were supported by the Medical Research Council (MRC, UK, MC_UP_1202/9) and the March of Dimes Foundation (FY11-436). We also thank Professor Steve Oliver and Dr. A.K.Hadjantonakis for helpful discussions and advice.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/stem.206

Self-organization of the in vitro attached human embryo

Implantation of the blastocyst is a developmental milestone in mammalian embryonic development. At this time, a coordinated program of lineage diversification, cell-fate specification, and morphogenetic movements establishes the generation of extra-embryonic tissues and the embryo proper, and determines the conditions for successful pregnancy and gastrulation. Despite its basic and clinical importance, this process remains mysterious in humans. Here we report the use of a novel in vitro system1,2 to study the post-implantation development of the human embryo. We unveil the self-organizing abilities and autonomy of in vitro attached human embryos. We find human-specific molecular signatures of early cell lineage, timing, and architecture. Embryos display key landmarks of normal development, including epiblast expansion, lineage segregation, bi-laminar disc formation, amniotic and yolk sac cavitation, and trophoblast diversification. Our findings highlight the species-specificity of these developmental events and provide a new understanding of early human embryonic development beyond the blastocyst stage. In addition, our study establishes a new model system relevant to early human pregnancy loss. Finally, our work will also assist in the rational design of differentiation protocols of human embryonic stem cells to specific cell types for disease modelling and cell replacement therapy

Assessment of renal damage in patients with multi-drug resistant strains of pneumonia treated with colistin

Background: Treatment of multi-drug-resistant strains of pneumonia with common antibiotics in renal patients is ine ective and physicians are compelled to use Colistin for such cases. Objectives: This study was conducted to assess the mortality, length of stay, and renal damages in the treatment of multi-drug-resistant pneumonia with Colistin among multiple trauma patients admitted to the emergency department and transferred to the ICU. Methods: This retrospective cohort study was conducted between 2011 and 2016. 102 multiple trauma (MT) patients with multidrug-resistant strains of hospital-acquired pneumonia (HAP) admitted to the emergency department then transferred to the ICU were assessed. All patients received Colistin according to their weight. Renal damage was evaluated according to the RIFLE criteria. The mortality and the length of stay were assessed. In order to statistically analyze the data, SPSS version 23 software was used to conduct t-test and chi-square test. Results: Out of 102 patients, 55 (54) died and 50 (49.1) developed acute renal failure; 64 cases had no hypertension. Patients according to the RIFLE index were assessed: Risk (11.01), Injury (14), Failure (18), Loss (6), and End-stage renal disease. The prevalence and prognosis of acute kidney injury in multiple trauma patients treated with Colistin were significantly correlated with drug dosage, body mass index, and use of corticosteroids (when assessed using relevant scoring systems, P < 0.05). Conclusions: The use of a scoring system in the intensive care unit, determining those patients requiring Colistin, and adjusting the dosage of this drug for treatment of MT patients with multi-drug resistant strains of HAP are vital. Creatinine levels must be carefully monitored. © 2018, Trauma Monthly

Dynamic Proteomic Profiling of Extra-Embryonic Endoderm Differentiation in Mouse Embryonic Stem Cells.

During mammalian preimplantation development, the cells of the blastocyst's inner cell mass differentiate into the epiblast and primitive endoderm lineages, which give rise to the fetus and extra-embryonic tissues, respectively. Extra-embryonic endoderm (XEN) differentiation can be modeled in vitro by induced expression of GATA transcription factors in mouse embryonic stem cells. Here, we use this GATA-inducible system to quantitatively monitor the dynamics of global proteomic changes during the early stages of this differentiation event and also investigate the fully differentiated phenotype, as represented by embryo-derived XEN cells. Using mass spectrometry-based quantitative proteomic profiling with multivariate data analysis tools, we reproducibly quantified 2,336 proteins across three biological replicates and have identified clusters of proteins characterized by distinct, dynamic temporal abundance profiles. We first used this approach to highlight novel marker candidates of the pluripotent state and XEN differentiation. Through functional annotation enrichment analysis, we have shown that the downregulation of chromatin-modifying enzymes, the reorganization of membrane trafficking machinery, and the breakdown of cell-cell adhesion are successive steps of the extra-embryonic differentiation process. Thus, applying a range of sophisticated clustering approaches to a time-resolved proteomic dataset has allowed the elucidation of complex biological processes which characterize stem cell differentiation and could establish a general paradigm for the investigation of these processes.This work was supported by the European Union 7th Framework Program (PRIME-XS project grant number 262067 to K.S.L., L.G and C.M.M), the Biotechnology and Biological Sciences Research Council (BBSRC grant number BB/L002817/1 to K.S.L and L.G.), as well as a HFSP grant (RGP0029/2010) and a European Research Council (ERC) Advanced Investigator grant to A.M.A.. C.S was supported by an EMBO long term fellowship and a Marie Curie IEF. L.T.Y.C. and K.K.N. were supported by the Medical Research Council (MRC, UK, MC_UP_1202/9) and the March of Dimes Foundation (FY11-436). We also thank Professor Steve Oliver and Dr. A.K.Hadjantonakis for helpful discussions and advice.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/stem.206

IGF1-mediated human embryonic stem cell self-renewal recapitulates the embryonic niche.

Our understanding of the signalling pathways regulating early human development is limited, despite their fundamental biological importance. Here, we mine transcriptomics datasets to investigate signalling in the human embryo and identify expression for the insulin and insulin growth factor 1 (IGF1) receptors, along with IGF1 ligand. Consequently, we generate a minimal chemically-defined culture medium in which IGF1 together with Activin maintain self-renewal in the absence of fibroblast growth factor (FGF) signalling. Under these conditions, we derive several pluripotent stem cell lines that express pluripotency-associated genes, retain high viability and a normal karyotype, and can be genetically modified or differentiated into multiple cell lineages. We also identify active phosphoinositide 3-kinase (PI3K)/AKT/mTOR signalling in early human embryos, and in both primed and naïve pluripotent culture conditions. This demonstrates that signalling insights from human blastocysts can be used to define culture conditions that more closely recapitulate the embryonic niche