Applications of nanomedicine in antibacterial medical therapeutics and diagnostics

The need for new and effective/efficient antibacterial therapeutics and diagnostics is necessary if we want to be able to maintain and improve the protection against pathogenic bacteria. Bacteria are becoming increasingly resistant to traditionally used antibiotics and as a result are a major health concern. The number of deaths and hospitalizations due to bacteria is increasing. Current methods of bacterial diagnostics are inefficient as they lack speed and ultra sensitivity and cannot be performed on site. This is where nanomedicine is playing a vital role. The discovery of new and innovative materials through the improvement in fabrication techniques has seen the establishment of an influx of novel antibacterial therapeutics and diagnostics. The goal of this review is to highlight the research that has been done through the implementation of nanomaterials and nanotechnologies for antibacterial medical therapeutic and diagnostic.<br /

Microbial-based therapy of cancer: a new twist to age old practice

The use of bacteria in the regression of tumors has long been known. Various approaches for using bacteria in cancer therapy include the use of bacteria as sensitizing agents for chemotherapy, as delivery agents for cancer drugs and as agents for gene therapy. The tumor regression stimulated by infecting microorganisms has been attributed to activation of the immune system of the host. However, recent studies indicate that when tumor-harboring mice with defective immune systems are infected with certain microorganisms, the regression of the tumor is still observed, suggesting that there are other host factors contributing to the microbial associated regression of tumors. Since the use of live or attenuated bacteria for tumor regression has associated toxic effects, studies are in progress to identify a pure microbial metabolite or any component of the microbial cell that might have anti-cancer activity. It has now been demonstrated that a redox protein from Pseudomonas aeruginosa, a cupredoxin, can enter into human cancer cells and trigger the apoptotic cell death. In vivo, this cupredoxin can lead to the regression of tumor growth in immunodeficient mice harboring xenografted melanomas and breast cancer tumors without inducing significant toxic effects, suggesting that it has potential anti-cancer activity. This bacterial protein interacts with p53 and modulates mammalian cellular activity. Hence, it could potentially be used as an anti-cancer agent for solid tumors and has translational value in tumor-targeted or in combinational-biochemotherapy strategies for cancer treatments. Here, we focus on diverse approaches to cancer biotherapy, including bacteriolytic and bacterially-derived anti-cancer agents with an emphasis on their mechanism of action and therapeutic potential

Efficient generation and transcriptomic profiling of human iPSC-derived pulmonary neuroendocrine cells

Expansion of pulmonary neuroendocrine cells (PNECs) is a pathological feature of many human lung diseases. Human PNECs are inherently difficult to study due to their rarity (\u3c1% of total lung cells) and a lack of established protocols for their isolation. We used induced pluripotent stem cells (iPSCs) to generate induced PNECs (iPNECs), which express core PNEC markers, including ROBO receptors, and secrete major neuropeptides, recapitulating known functions of primary PNECs. Furthermore, we demonstrate that differentiation efficiency is increased in the presence of an air-liquid interface and inhibition of Notch signaling. Single-cell RNA sequencing (scRNA-seq) revealed a PNEC-associated gene expression profile that is concordant between iPNECs and human fetal PNECs. In addition, pseudotime analysis of scRNA-seq results suggests a basal cell origin of human iPNECs. In conclusion, our model has the potential to provide an unlimited source of human iPNECs to explore PNEC pathophysiology associated with several lung diseases

Epigenetic changes in myelofibrosis:Distinct methylation changes in the myeloid compartments and in cases with <i>ASXL1</i> mutations

Abstract This is the first study to compare genome-wide DNA methylation profiles of sorted blood cells from myelofibrosis (MF) patients and healthy controls. We found that differentially methylated CpG sites located to genes involved in ‘cancer’ and ‘embryonic development’ in MF CD34+ cells, in ‘inflammatory disease’ in MF mononuclear cells, and in ‘immunological diseases’ in MF granulocytes. Only few differentially methylated CpG sites were common among the three cell populations. Mutations in the epigenetic regulators ASXL1 (47%) and TET2 (20%) were not associated with a specific DNA methylation pattern using an unsupervised approach. However, in a supervised analysis of ASXL1 mutated versus wild-type cases, differentially methylated CpG sites were enriched in regions marked by histone H3K4me1, histone H3K27me3, and the bivalent histone mark H3K27me3 + H3K4me3 in human CD34+ cells. Hypermethylation of selected CpG sites was confirmed in a separate validation cohort of 30 MF patients by pyrosequencing. Altogether, we show that individual MF cell populations have distinct differentially methylated genes relative to their normal counterparts, which likely contribute to the phenotypic characteristics of MF. Furthermore, differentially methylated CpG sites in ASXL1 mutated MF cases are found in regulatory regions that could be associated with aberrant gene expression of ASXL1 target genes

A Computational Profiling of Changes in Gene Expression and Transcription Factors Induced by vFLIP K13 in Primary Effusion Lymphoma

Infection with Kaposi's sarcoma associated herpesvirus (KSHV) has been linked to the development of primary effusion lymphoma (PEL), a rare lymphoproliferative disorder that is characterized by loss of expression of most B cell markers and effusions in the body cavities. This unique clinical presentation of PEL has been attributed to their distinctive plasmablastic gene expression profile that shows overexpression of genes involved in inflammation, adhesion and invasion. KSHV-encoded latent protein vFLIP K13 has been previously shown to promote the survival and proliferation of PEL cells. In this study, we employed gene array analysis to characterize the effect of K13 on global gene expression in PEL-derived BCBL1 cells, which express negligible K13 endogenously. We demonstrate that K13 upregulates the expression of a number of NF-κB responsive genes involved in cytokine signaling, cell death, adhesion, inflammation and immune response, including two NF-κB subunits involved in the alternate NF-κB pathway, RELB and NFKB2. In contrast, CD19, a B cell marker, was one of the genes downregulated by K13. A comparison with K13-induced genes in human vascular endothelial cells revealed that although there was a considerable overlap among the genes induced by K13 in the two cell types, chemokines genes were preferentially induced in HUVEC with few exceptions, such as RANTES/CCL5, which was induced in both cell types. Functional studies confirmed that K13 activated the RANTES/CCL5 promoter through the NF-κB pathway. Taken collectively, our results suggest that K13 may contribute to the unique gene expression profile, immunophenotype and clinical presentation that are characteristics of KSHV-associated PEL

Análise da evolução do índice de bem-estar econômico sustentável modificado no Brasil entre 2004 e 2014.

TCC (graduação) - Universidade Federal de Santa Catarina. Centro Sócio-Econômico. Economia.A preocupação com o Meio Ambiente é um assunto cada vez mais abordado na economia. Diversos conceitos de desenvolvimento sustentável e sustentabilidade estão estabelecidos. Juntamente com a evolução dos conceitos, criou-se diversas maneiras de mensurar o desenvolvimento sustentável para tentar explicar o bem-estar de uma maneira mais abrangente que os indicadores convencionais. O IBEESm desenvolveu-se por uma inspiração a partir das mudanças na metodologia dos índices desenvolvidos anteriormente. O objetivo principal deste trabalho é analisar o comportamento do Índice de Bem-Estar Econômico Sustentável Modificado no Brasil no período entre 2004 e 2014 e comparar com os indicadores convencionais, PIB e IDH, para verificar a abrangência de sua explicação na questão do bem-estar econômico sustentável. Primeiramente, o estudo partiu de concepções teóricas documentais referentes ao tema de economia do meio ambiente relacionada à criação de índices de Bem-Estar econômico e sustentável. Realizou-se um levantamento de dados secundários em fontes oficiais e estimou-se empiricamente, por meio da Análise dos Componentes Principais o índice para o Brasil a partir da metodologia construída. A decomposição do índice para análise do comportamento das variáveis dentro das dimensões permitiu avaliar o impacto de cada uma em relação ao bem-estar. Conclui-se, a partir das análises, que o bem-estar econômico sustentável é melhor explicado quando abordadas as suas três dimensões. Conclui-se também que o desmatamento é uma medida importante para o bem-estar no Brasil. Constatou-se, por fim, que os indicadores convencionais não captam todas as mudanças referentes, especialmente, ao meio ambiente

Dehydroepiandrosterone inhibits the progression phase of mammary carcinogenesis by inducing cellular senescence via a p16-dependent but p53-independent mechanism

INTRODUCTION: Dehydroepiandrosterone (DHEA), an adrenal 17-ketosteroid, is a precursor of testosterone and 17β-estradiol. Studies have shown that DHEA inhibits carcinogenesis in mammary gland and prostate as well as other organs, a process that is not hormone dependent. Little is known about the molecular mechanisms of DHEA-mediated inhibition of the neoplastic process. Here we examine whether DHEA and its analog DHEA 8354 can suppress the progression of hyperplastic and premalignant (carcinoma in situ) lesions in mammary gland toward malignant tumors and the cellular mechanisms involved. METHODS: Rats were treated with N-nitroso-N-methylurea and allowed to develop mammary hyperplastic and premalignant lesions with a maximum frequency 6 weeks after carcinogen administration. The animals were then given DHEA or DHEA 8354 in the diet at 125 or 1,000 mg/kg diet for 6 weeks. The effect of these agents on induction of apoptosis, senescence, cell proliferation, tumor burden and various effectors of cellular signaling were determined. RESULTS: Both agents induced a dose-dependent decrease in tumor multiplicity and in tumor burden. In addition they induced a senescent phenotype in tumor cells, inhibited cell proliferation and increased the number of apoptotic cells. The DHEA-induced cellular effects were associated with increased expression of p16 and p21, but not p53 expression, implicating a p53-independent mechanism in their action. CONCLUSION: We provide evidence that DHEA and DHEA 8354 can suppress mammary carcinogenesis by altering various cellular functions, inducing cellular senescence, in tumor cells with the potential involvement of p16 and p21 in mediating these effects

K13 blocks KSHV lytic replication and deregulates vIL6 nad hIL6 expression: A model of lytic replication induced clonal selection in viral oncogenesis

Background. Accumulating evidence suggests that dysregulated expression of lytic genes plays an important role in KSHV (Kaposi's sarcoma associated herpesvirus) tumorigenesis. However, the molecular events leading to the dysregulation of KSHV lytic gene expression program are incompletely understood. Methodoloxy/Principal Findings. We have studied the effect of KSHV-encoded latent protein vFLIP K13, a potent activator of the NF-κB pathway, on lytic reactivation of the virus. We demonstrate that K13 antagonizes RTA, the KSHV lytic-regulator, and effectively blocks the expression of lytic proteins, production of infectious virions and death of the infected cells. Induction of lytic replication selects for clones with increased K13 expression and NF-κB activity, while siRNA-mediated silencing of K13 induces the expression of lytic genes. However, the suppressive effect of K13 on RTA-induced lytic genes is not uniform and it falls to block RTA-induced viral IL6 secretion and cooperates with RTA to enhance cellular IL-6 production, thereby dysregulating the lytic gene expression program. Conclusions/Significance. Our results support a model in which ongoing KSHV, lytic replication selects for clones with progressively higher levels of K13 expression and NF-κB activity, which in turn drive KSHV tumorigenesis by not only directly stimulating cellular survival and proliferation, but also indirectly by dysregulating the viral lytic gene program and allowing non-lytic production of growth-promoting viral and cellular genes. Lytic Replication-Induced Clonal Selection (LyRICS) may represent a general mechanism in viral oncogenesis. 2007 Zhao et al

Re:GEN Open: The Impact of Genomics and Biotechnology on the Future of Medicine

Modern technological advances, like the unraveling of the human genome, high-throughput cellular processes, etc., have ushered in an era with renewed hope for better health for the world. Sophisticated tools have been developed for diagnosing, curing, and preventing diseases. There has been extraordinary development in understanding the human genome and its role in health and disease. A decade ago, researchers tentatively explored the first reference human genome at the cost of more than $1 billion. However, now thousands of genomes from different ethnic backgrounds have been sequenced. This explosion of sequencing has been enabled by unprecedented advances in sequencing technologies that can now sequence a person?s entire genome within a day at a nominal cost of$1,000 (or less). Technology advances enable an ever?increasing capacity to diagnose existing diseases and develop novel treatment strategies accurately. Such technologies also offer clinicians the opportunities to identify potential biomarkers. However, the enormous information generated from these technologies has posed challenging propositions to develop novel practical biotechnology and medicine applications. Although our knowledge of the human genome is far from complete, accumulating examples demonstrate that even our limited genomic understanding can have robust clinical implications. From stem cell therapy to improved blood tests to a variety of pharmaceuticals, the face of healthcare has been changed by biotechnology. Biotechnology companies use microbes to create new therapeutic agents, such as monoclonal antibodies, antibiotics, vaccines, and hormones. Five years ago, scientists at J. Craig Venter Institute collaborated with researchers at MIT to develop an artificial cell with only 473 genes. This genetically engineered simplest bacterium is considered one of the pillars of synthetic biology. Introducing Re:GEN Open Given the exciting state of affairs in biomedical research, I am particularly excited to be named as founding editor of the new multidisciplinary open-access journal, Re:GEN Open. I have always been interested in studying the role of genomics in translational research. I started in genomic projects at the University of Illinois at Chicago and worked on microbial virulence factors and their role in cancer. I learned some of the critical intricacies of the genome from my mentor, A.M. Chakrabarty. Dr. Chakrabarty is credited with creating and patenting the first genetically engineered oil-eating bacterium?Pseudomonas aeruginosa?which revolutionized genetic engineering and biotechnology. I continued my work on the relationship of microorganisms with cancer at the University of Pittsburgh focusing on viral-mediated oncogenesis in various malignancies. During that time, massively parallel sequencing was taking off, and I focused on human genome sequencing and its relation to the development and progression of cancer. My work took me deep into synthetic and systems biology at the University of Southern California. My current research focuses on developing genomic-based precision medicine strategies for various diseases, emphasizing biomarker discovery. I have been on many adventures in the genomics industry and have helped people by providing potential precision medicine solutions. Re:GEN Open is unique because it combines different biomedical research areas in a single forum. We hope to attract stakeholders in academia, industry, as well as medical professionals around the world. We would love to hear from researchers and professionals who are innovators in drug development, stem cell or DNA/RNA-based therapies, and their patient-specific studies. The journal will cover all aspects of basic and translational biomedical research under eight broad sections: Basic Biomedical Research Translational Biomedical Research Drug Development Cancer Research Regenerative Medicine Cell and Gene Therapy Infectious Disease Synthetic and Systems Biology Synthetic biotechnology is reshaping the way humans live, but only a few journals are dedicated to this field. Therefore, we have a separate section dedicated to this evolving branch of biotechnology. In launching Re:GEN Open, I envisage the journal playing a central role in supporting the rapid development of the genetic engineering and biotechnology field in which we operate. To achieve this, we will: make effective and speedy editorial decisions; expand our presence in emerging and developing areas of genetic engineering and biotechnology; work with the editorial advisory board to champion new and emerging fields and scale the journal ranks in these areas; strengthen and facilitate our relationship with many other fine journals published by Mary Ann Liebert Inc., publishers, by allowing the transfer of quality papers to Re:GEN Open. With our publisher?s continued support, we will aim for the highest standards in the journal?s management and operations; give priority to papers that are scientifically rigorous and make a significant advance in the biomedical sciences and publish them after one round of reviews; and consider manuscripts that have been reviewed and rejected by leading journals such as Nature, Science, PNAS, JCI, etc. Based on reviewers? and authors? rebuttal comments, the AEs will advise if the manuscript needs further review or can be published directly. It is an honor and privilege for me to work alongside incoming editorial board members representing a broad and diverse group of scientists with varied intellectual interests and career paths. Our editorial board members have volunteered their expertise and time. They are committed to making Re:GEN Open the best journal publishing studies of the impact on biotechnology on biomedical sciences. I shall be seeking their advice to improve the journal?s standing, exploring developing areas in genetic engineering, biotechnology, and the life sciences. In addition to our balance in the editorial team, we are committed to providing fair and rigorous but timely peer review. Our processes will ensure fairness and trust from submission to final decision. Open Access Re:GEN Open is a fully open access journal. To promote unhindered dissemination of laboratory research, we will support the principles of open access to all colleagues across the world, regardless of their financial or educational background. We also believe in open data sharing to ensure reproducibility in published results. Open access publications can reduce some of the barriers in sharing data, protocols, and source codes. Articles will be swiftly posted on the journal?s website upon acceptance and be freely available. In conclusion, I hope you enjoy reading some of our first published articles and look forward to many more exciting articles in the months and years to come. I hope you will want to shape and develop the journal in the future with your discoveries. Most importantly, please share your thoughts about Re:GEN Open with your colleagues and contribute your research to our journal so we may learn together and make the world healthier. Finally, I would like to remind the journal?s readers that this journal belongs to you. If you have any suggestions or constructive criticism that may help our team improve any aspects of our journal, please email us at [email protected]. You can also send us presubmission inquiries to this email to check whether your next manuscript is a good fit. Cheers! Vasu Pun