miRNA

RNA interference (RNAi) is an effective and important tool used to study gene function. For large-scale screens, RNAi is used to systematically down-regulate genes of interest and analyze their roles in a biological process. However, RNAi is associated with off-target effects (OTEs), including microRNA (miRNA)-like OTEs. The contribution of reagent-specific OTEs to RNAi screen data sets can be significant. In addition, the post-screen validation process is time and labor intensive. Thus, the availability of robust approaches to identify candidate off-targeted transcripts would be beneficial. Significant efforts have been made to eliminate false positive results attributable to sequence-specific OTEs associated with RNAi. These approaches have included improved algorithms for RNAi reagent design, incorporation of chemical modifications into siRNAs, and the use of various bioinformatics strategies to identify possible OTEs in screen results. Genome-wide Enrichment of Seed Sequence mat...

A flexible graphene field-effect transistor (Gr-FET) biosensor for ultrasensitive and specific detection of miRNA without labeling and functionalization is reported. The flexible biosensor presents robust performance even after multiple cycles bending to cylinder with 8 mm radius. DNA probe is designed with partial segment complementary to target miRNA, and immobilized on the graphene surface though π-π stacking interaction. After capture of target miRNA, Dirac point shift in Gr-FET is induced, which shows a linear relationship with target miRNA concentration in semi-log scale. Gr-FET based biosensor finishes miRNA detection in 20 min, and is able to achieve a miRNA detection limit as low as 1 fM without any functionalization and labeling. The interaction processes of DNA-graphene and DNA-miRNA are confirmed through surface enhanced Raman scattering technology. The proposed biosensor will have prospective applications in wearable electronics for health monitoring and diseases diagnosis.

Objectives: Exosomes are small membrane bound vesicles secreted by most cell types. Exosomes contain various functional proteins, mRNAs and microRNAs (miRNAs) that could be used for diagnostic and therapeutic purposes. Currently, a standard method for serum exosome isolation is differential ultracentrifugation, but a search for alternative, less time-consuming and labour extensive exosomal isolation method for use in clinical settings is ongoing. The effect of serum exosome isolation method on obtained miRNA profile is not yet clear. The aim of this study was to determine to which extent selected exosome isolation methods influence the serum exosomal miRNA profile. Design and methods: Exosomes were isolated from blood serum of healthy individuals by ultracentrifuga-tion and ExoQuick Precipitation methods. The expression profile of 375 miRNAs was determined by real time PCR using Exiqon miRCURY LNA™ microRNA Human panel I assays. Results: Although a strong correlation of exosomal miRNA profiles was observed between the two isolation methods, distinct clusters of miRNA levels between the used methods were identified. The detected levels of two miRNAs, miR-92a and miR-486-5p, were significantly influenced by the exosome isolation method used. Conclusions: Both exosome isolation methods are suitable for serum exosomal miRNA profiling. Differences found in miRNA patterns between the two methods indicate that the observed exosomal miRNA profile is slightly affected by the extracellular vesicle isolation method.

MicroRNAs (miRNAs) are endogenous, non-coding RNAs, which have evoked a great deal of interest due to their importance in many aspects of homeostasis and diseases. MicroRNAs are
stable and are essential components of gene regulatory networks. They play a crucial role in healthy individuals and their dysregulations have also been implicated in a wide range of
diseases, including diabetes, cardiovascular disease, kidney disease, and cancer. This review summarized the current understanding of interactions between miRNAs and different diseases and their role in disease diagnosis and therapy.

We present a general computational theory of cancer and its developmental dynamics. The theory is based on a theory of the architecture and function of developmental control networks which guide the formation of multicellular organisms. Cancer networks are special cases of developmental control networks. Cancer results from transformations of normal developmental networks. Our theory generates a natural classification of all possible cancers based on their network architecture. Each cancer network has a unique topology and semantics and developmental dynamics that result in distinct clinical tumor phenotypes. We apply this new theory with a series of proof of concept cases for all the basic cancer types. These cases have been computationally modeled, their behavior simulated and mathematically described using a multicellular systems biology approach. There are fascinating correspondences between the dynamic developmental phenotype of computationally modeled {\em in silico} cancers a...

Nanotechnology, which deals with features as small as a 1 billionth of a meter, began to enter into mainstream physical sciences and engineering some 20 years ago. Recent applications of nanoscience include the use of nanoscale materials in electronics, catalysis, and biomedical research. Among these applications, strong interest has been shown to biological processes such as blood coagulation control and multimodal bioimaging, which has brought about a new and exciting research field called nanobiotechnology. Biotechnology, which itself also dates back ∼30 years, involves the manipulation of macroscopic biological systems such as cells and mice in order to understand why and how molecular level mechanisms affect specific biological functions, e.g., the role of APP (amyloid precursor protein) in Alzheimer’s disease (AD). This review aims (1) to introduce key concepts and materials from nanotechnology to a non-physical sciences community; (2) to introduce several state-of-the-art examples of current nanotechnology that were either constructed for use in biological systems or that can, in time, be utilized for biomedical research; (3) to provide recent excerpts in nanotoxicology and multifunctional nanoparticle systems (MFNPSs); and (4) to propose areas in neuroscience that may benefit from research at the interface of neurobiologically important systems and nanostructured materials.

Médico Especialista Álvaro Miguel Carranza Montalvo, soy Médico General Alto, Rubio, de Piel Blanca, ojos claros , soy Atlético Simpático, me esmero a seguir Adelante solucionando los Problemas de las demás Personas para salvar su Vida en Salud y en Enfermedades. Internet, Networds….
Médico Especialista Álvaro Miguel Carranza Montalvo, la VIDA es una VIRTUD que cada Humano, Persona tiene es Valeroso y Digno lograr SALVAR la VIDA de una Persona que está en Peligro, cada Persona es una sóla Unidad único no hay nadie como esa persona somos distintos. Internet, Networds….
Médico Especialista Álvaro Miguel Carranza Montalvo, la NATURALEZA es Bella y Linda Vivirla al Aire Libre, con Agua, la Vegetación, los Bellos Animales en el Ecosistema la Biodiversidad hay que Valorar y Gozar lo que hay en el Mundo Vivirla y Disfrutarla. Internet, Networds….
Médico Especialista Álvaro Miguel Carranza Montalvo, ME GUSTA LO QUE SOY MI FORMA DE SER ME ENCANTA LO QUE SOY YÓ MI FÍSICO, MENTE, PENSAMIENTOS, ALMA Y CUERPO, FÍSICO.  Y VIVIR LA VIDA, NATURALEZA LA BELLEZA. Web, Redes Sociales….
Médico Especialista Álvaro Miguel Carranza Montalvo, Me gusta la Naturaleza y la Vida. VIVIR LA VIDA RESPETANDO A LOS DEMÁS CHICAS Y CHICOS A TODAS LAS PERSONAS LES RESPETO Y ADMIRO PORQUE TIENEN SUS VALORES Y DONES. HACER EL BIEN NUNCA EL MAL A LA PERSONA TRATAR COMO A UNO LE GUSTARÍA QUE LE TRATEN. Web, Redes Sociales….
Médico Especialista Álvaro Miguel Carranza Montalvo, "creo que las artes marciales mixtas sirven principalmente para desarrollar la energía. A veces es necesario darse cuenta de un peligro y conocer el medio para salvar la vida. Web, Redes Sociales….
Médico Especialista Álvaro Miguel Carranza Montalvo, La Energía es Vital para lograr una Meta con Fuerza y Salud es lo más Importante en la Vida. ", Web, Internet….
Médico Especialista Álvaro Miguel Carranza Montalvo, "es necesario realizar ejercicios determinados en la columna, para proporcionar oxígeno al cerebro y ayudarle a descansar totalmente", Web, Internet….
Médico Especialista Álvaro Miguel Carranza Montalvo, "hay tres palabras que aprendemos a gritar que llevan consigo descanso y energía; fuerza, valor y convicción", Web, Internet….

Національний університет біоресурсів і природокористування України НДІ фітомедицини, біотехнологій та екології Факультет захисту рослин, біотехнологій та екології Агенство з трансферу технологій, освіти і науки daRostim Німецький приватний інститут прикладної біотехнології daRostim БІОЛОГІЧНО АКТИВНІ ПРЕПАРАТИ В РОСЛИННИЦТВІ НАУКОВЕ ОБҐРУНТУВАННЯ-РЕКОМЕНДАЦІЇ-ПРАКТИЧНІ РЕЗУЛЬТАТИ Матеріали XV Міжнародної науково-практичної конференції Київ, 25-29 червня 2019 року

The frontline of plant defense against non-viral pathogens such as bacteria, fungi and oomycetes is provided by transmembrane pattern recognition receptors that detect conserved pathogen-associated molecular patterns (PAMPs), leading to pattern-triggered immunity (PTI). To counteract this innate defense, pathogens deploy effector proteins with a primary function to suppress PTI. In specific cases, plants have evolved intracellular resistance (R) proteins detecting isolate-specific pathogen effectors, leading to effector-triggered immunity (ETI), an amplified version of PTI, often associated with hypersensitive response (HR) and programmed cell death (PCD). In the case of plant viruses, no conserved PAMP was identified so far and the primary plant defense is thought to be based mainly on RNA silencing, an evolutionary conserved, sequence-specific mechanism that regulates gene expression and chromatin states and represses invasive nucleic acids such as transposons. Endogenous silencin...

Tissue engineering is a newly emerging biomedical technology, which aids and increases the repair and regeneration of deficient and injured tissues. It employs the principles from the fields of materials science, cell biology, transplantation, and engineering in an effort to treat or replace damaged tissues. Tissue engineering and development of complex tissues or organs, such as heart, muscle, kidney, liver, and lung, are still a distant milestone in twenty-first century. Generally, there are four main challenges in tissue engineering which need optimization. These include biomaterials, cell sources, vascularization of engineered tissues, and design of drug delivery systems. Biomaterials and cell sources should be specific for the engineering of each tissue or organ. On the other hand, angiogenesis is required not only for the treatment of a variety of ischemic conditions, but it is also a critical component of virtually all tissue-engineering strategies. Therefore, controlling the dose, location, and duration of releasing angiogenic factors via polymeric delivery systems, in order to ultimately better mimic the stem cell niche through scaffolds, will dictate the utility of a variety of biomaterials in tissue regeneration. This review focuses on the use of polymeric vehicles that are made of synthetic and/or natural biomaterials as scaffolds for three-dimensional cell cultures and for locally delivering the inductive growth factors in various formats to provide a method of controlled, localized delivery for the desired time frame and for vascularized tissue-engineering therapies.

Médico Especialista Álvaro Miguel Carranza Montalvo, soy Médico General Alto, Rubio, de Piel Blanca, ojos claros , soy Atlético Simpático, me esmero a seguir Adelante solucionando los Problemas de las demás Personas para salvar su Vida en Salud y en Enfermedades. Internet, Networds….
Médico Especialista Álvaro Miguel Carranza Montalvo, la VIDA es una VIRTUD que cada Humano, Persona tiene es Valeroso y Digno lograr SALVAR la VIDA de una Persona que está en Peligro, cada Persona es una sóla Unidad único no hay nadie como esa persona somos distintos. Internet, Networds….
Médico Especialista Álvaro Miguel Carranza Montalvo, la NATURALEZA es Bella y Linda Vivirla al Aire Libre, con Agua, la Vegetación, los Bellos Animales en el Ecosistema la Biodiversidad hay que Valorar y Gozar lo que hay en el Mundo Vivirla y Disfrutarla. Internet, Networds….
Médico Especialista Álvaro Miguel Carranza Montalvo, ME GUSTA LO QUE SOY MI FORMA DE SER ME ENCANTA LO QUE SOY YÓ MI FÍSICO, MENTE, PENSAMIENTOS, ALMA Y CUERPO, FÍSICO.  Y VIVIR LA VIDA, NATURALEZA LA BELLEZA. Web, Redes Sociales….
Médico Especialista Álvaro Miguel Carranza Montalvo, Me gusta la Naturaleza y la Vida. VIVIR LA VIDA RESPETANDO A LOS DEMÁS CHICAS Y CHICOS A TODAS LAS PERSONAS LES RESPETO Y ADMIRO PORQUE TIENEN SUS VALORES Y DONES. HACER EL BIEN NUNCA EL MAL A LA PERSONA TRATAR COMO A UNO LE GUSTARÍA QUE LE TRATEN. Web, Redes Sociales….
Médico Especialista Álvaro Miguel Carranza Montalvo, "creo que las artes marciales mixtas sirven principalmente para desarrollar la energía. A veces es necesario darse cuenta de un peligro y conocer el medio para salvar la vida. Web, Redes Sociales….
Médico Especialista Álvaro Miguel Carranza Montalvo, La Energía es Vital para lograr una Meta con Fuerza y Salud es lo más Importante en la Vida. ", Web, Internet….
Médico Especialista Álvaro Miguel Carranza Montalvo, "es necesario realizar ejercicios determinados en la columna, para proporcionar oxígeno al cerebro y ayudarle a descansar totalmente", Web, Internet….
Médico Especialista Álvaro Miguel Carranza Montalvo, "hay tres palabras que aprendemos a gritar que llevan consigo descanso y energía; fuerza, valor y convicción", Web, Internet….

The amount and distribution of dystrophin protein in myofibers and muscle is highly variable in Becker muscular dystrophy and in exon-skipping trials for Duchenne muscular dystrophy. Here, we investigate a molecular basis for this variability. In muscle from Becker patients sharing the same exon 45-47 in-frame deletion, dystrophin levels negatively correlate with microRNAs predicted to target dystrophin. Seven microRNAs inhibit dystrophin expression in vitro, and three are validated in vivo (miR-146b/miR-374a/miR-31). microRNAs are expressed in dystrophic myofibers and increase with age and disease severity. In exon-skipping-treated mdx mice, microRNAs are significantly higher in muscles with low dystrophin rescue. TNF-α increases microRNA levels in vitro whereas NFκB inhibition blocks this in vitro and in vivo. Collectively, these data show that microRNAs contribute to variable dystrophin levels in muscular dystrophy. Our findings suggest a model where chronic inflammation in distinct microenvironments induces pathological microRNAs, initiating a self-sustaining feedback loop that exacerbates disease progression.

Micro-RNAs (miRNA) are functional, non-protein coding RNA molecules that are approximately 22 nucleotides in length and their transcriptions provided by intron or exon regions of the genome and non-protein coding regions of RNA genes. miRNAs inhibit translation of protein and destroy mRNA. Although approximately 2500 human miRNA types have been
identified so far, quite little is known about their biological functions. In some studies, it is shown that miRNA expression levels are important for many biological processes such as cell proliferation, differentiation, apoptosis, organogenesis and metabolism. Recent studies have pointed out that miRNAs have been used as diagnosis and prognosis biomarkers in many human diseases including cancer, cardiovascular disorders, cerebrovascular disorders and metabolic disturbances.

According to the World Health Organization, cardiovascular disease accounts for approximately 30% of all deaths in the United States, and is the worldwide leading cause of morbidity and mortality. Over the last several years, microRNAs have emerged as critical regulators of physiological homeostasis in multiple organ systems, including the cardiovascu-lar system. The focus of this review is to provide an overview of the current state of knowledge of the molecular mechanisms contributing to the multiple causes of cardiovascular disease with respect to regulation by microRNAs. A major challenge in understanding the roles of microRNAs in the pathophysiology of cardiovascular disease is that cardiovascular disease may arise from perturbations in intracellular signaling in multiple cell types including vascular smooth muscle and endothelial cells, cardiac myocytes and fibroblasts, as well as hepatocytes, pancreatic b-cells, and others. Additionally, perturbations in intracellular signaling cascades may also have profound effects on heterocellular communication via secreted cytokines and growth factors. There has been much progress in recent years to identify the microRNAs that are both dysregulated under pathological conditions, as well as the signaling pathway(s) regulated by an individual microRNA. The goal of this review is to summarize what is currently known about the mechanisms whereby microRNAs maintain cardiovascular homeostasis and to attempt to identify some key unresolved questions that require further study.

Individuals with 22q11.2 microdeletions show behavioral and cognitive deficits and are at high risk of developing schizophrenia. We analyzed an engineered mouse strain carrying a chromosomal deficiency spanning a segment syntenic to the human 22q11.2 locus. We uncovered a previously unknown alteration in the biogenesis of microRNAs (miRNAs) and identified a subset of brain miRNAs affected by the microdeletion. We provide evidence that the abnormal miRNA biogenesis emerges because of haploinsufficiency of the Dgcr8 gene, which encodes an RNA-binding moiety of the 'microprocessor' complex and contributes to the behavioral and neuronal deficits associated with the 22q11.2 microdeletion.

Polyglutamine (polyQ) diseases are incurable neurological disorders caused by CAG repeat expansion in the open reading frames (ORFs) of specific genes. This type of mutation in the HTT gene is responsible for Huntington's disease (HD). CAG repeat-targeting artificial miRNAs (art-miRNAs) were shown as attractive therapeutic approach for polyQ disorders as they caused allele-selective decrease in the level of mutant proteins. Here, using polyQ disease models, we aimed to demonstrate how miRNA-based gene expression regulation is dependent on target sequence features. We show that the silencing efficiency and selectivity of art-miRNAs is influenced by the localization of the CAG repeat tract within transcript and the specific sequence context. Furthermore, we aimed to reveal the events leading to downregulation of mutant polyQ proteins and found very rapid activation of translational repression and HTT transcript deadenylation. Slicer-activity of AGO2 was dispensable in this process, as determined in AGO2 knockout cells generated with CRISPR-Cas9 technology. We also showed highly allele-selective downregulation of huntingtin in human HD neural progenitors (NPs). Taken together, art-miRNA activity may serve as a model of the cooperative activity and targeting of ORF regions by endogenous miRNAs.

Extracellular vesicles (EVs), including exosomes and microvesicles, are critical mediators of cell-to-cell communication in tissue homeostasis and repair, both in physiological and pathological conditions.
Recently, progress has been achieved in their use in regenerative medicine as transfer agents for active biomolecules. Specifically, EVs are natural carriers of microRNAs (miRNAs), protecting their cargo from plasma ribonucleases and delivering their content to recipient cells. Expression of miRNAs is dysregulated in virtually all forms of cancer. Therefore, EVs-mediated miRNA delivery may represent a valuable tool
for cancer therapeutic intervention, aiming at restoring cancer miRNAs expression to normal levels.
MicroRNAs may act both as tumor suppressors or oncogenes, consequently different alternative approaches for regulating miRNA expression in tumor tissues have been developed. Here, we review the various strategies for miRNA loading into EVs and highlight studies of EVs-mediated miRNA delivery which have been employed for cancer treatment, both in vitro and in vivo. Collectively, these data support the use of EVs in miRNAs/miRNAs antagonist transfer for cancer therapy, but challenges related to EV biology have yet to be further addressed before safe clinical translation.