Prebiotic RNA self-assembling and the origin of life: Mechanistic and molecular modeling rationale for explaining the prebiotic origin and replication of RNA.

In recent years, a great interest has been focused on the prebiotic origin of nucleic acids and life on Earth. An attractive idea is that life was initially based on an autocatalytic and autoreplicative RNA (the RNA-world). RNA duplexes are right-handed helical chains with antiparallel orientation, but the rationale for these features is not yet known.

Acridine orange fluorescence in chromosome cytochemistry: Molecular modeling rationale for understanding the differential fluorescence on double- and single-stranded nucleic acids.

Many fluorophores display interesting features that make them useful biological labels and dyes, particularly in Cell Biology and Cytogenetics. Changes in the absorption-emission spectra (ortho- and metachromasia) are accounted among them. Acridine orange (AO) is one of such fluorochromes with an exemplary orthochromatic vs.

How to Target Small-Molecule Fluorescent Imaging Probes to the Plasma Membrane-The Influence and QSAR Modelling of Amphiphilicity, Lipophilicity, and Flip-Flop.

Many new fluorescent probes targeting the plasma membrane (PM) of living cells are currently being described. Such probes are carefully designed to report on relevant membrane features, but oddly, the structural features required for effective and selective targeting of PM often receive less attention, constituting a lacuna in the molecular design process. We aim to rectify this by clarifying how the amphiphilicity and lipophilicity of a probe, together with the tendency to flip-flop across the membrane, contribute to selective PM accumulation.

Comparative proteomic profiling of uric acid, ammonium acid urate, and calcium-based kidney stones.

Introduction: Kidney stone matrix proteins may help explain cellular mechanisms of stone genesis. However, most existing proteomic studies have focused on calcium oxalate stones. Here, we present a comparative proteomic analysis of different kidney stone types.

Fluorescence labeling of mitochondria in living cells by the cationic photosensitizer ZnTM2,3PyPz, and the possible roles of redox processes and pseudobase formation in facilitating dye uptake.

The study of labeling selectivity and mechanisms of fluorescent organelle probes in living cells is of continuing interest in biomedical sciences. The tetracationic phthalocyanine-like ZnTM2,3PyPz photosensitizing dye induces a selective violet fluorescence in mitochondria of living HeLa cells under UV excitation that is due to co-localization of the red signal of the dye with NAD(P)H blue autofluorescence. Both red and blue signals co-localize with the green emission of the mitochondria probe, rhodamine 123.

Role of α- and β-adrenergic signaling in phenotypic targeting: significance in benign and malignant urologic disease.

The urinary tract is highly innervated by autonomic nerves which are essential in urinary tract development, the production of growth factors, and the control of homeostasis. These neural signals may become dysregulated in several genitourinary (GU) disease states, both benign and malignant. Accordingly, the autonomic nervous system is a therapeutic target for several genitourinary pathologies including cancer, voiding dysfunction, and obstructing nephrolithiasis.

Non-Coding RNAs Set a New Phenotypic Frontier in Prostate Cancer Metastasis and Resistance.

Prostate cancer (PCa) mortality remains a significant public health problem, as advanced disease has poor survivability due to the development of resistance in response to both standard and novel therapeutic interventions. Therapeutic resistance is a multifaceted problem involving the interplay of a number of biological mechanisms including genetic, signaling, and phenotypic alterations, compounded by the contributions of a tumor microenvironment that supports tumor growth, invasiveness, and metastasis. The androgen receptor (AR) is a primary regulator of prostate cell growth, response and maintenance, and the target of most standard PCa therapies designed to inhibit AR from interacting with androgens, its native ligands.

Plasmonic Hot-Electron Reactive Oxygen Species Generation: Fundamentals for Redox Biology.

For decades, the possibility to generate Reactive Oxygen Species (ROS) in biological systems through the use of light was mainly restricted to the photodynamic effect: the photoexcitation of molecules which then engage in charge- or energy-transfer to molecular oxygen (O) to initiate ROS production. However, the classical photodynamic approach presents drawbacks, like chemical reactivity of the photosensitizing agent or fast molecular photobleaching due to ROS generation, to name a few. Recently, a new approach, which promises many advantages, has entered the scene: plasmon-driven hot-electron chemistry.

Automated measurement of long-term bower behaviors in Lake Malawi cichlids using depth sensing and action recognition.

In the wild, behaviors are often expressed over long time periods in complex and dynamic environments, and many behaviors include direct interaction with the environment itself. However, measuring behavior in naturalistic settings is difficult, and this has limited progress in understanding the mechanisms underlying many naturally evolved behaviors that are critical for survival and reproduction. Here we describe an automated system for measuring long-term bower construction behaviors in Lake Malawi cichlid fishes, in which males use their mouths to sculpt sand into large species-specific structures for courtship and mating.

Lipid Peroxidation Assay Using BODIPY-Phenylbutadiene Probes: A Methodological Overview.

The assessment of reactive oxygen species has increasing importance in biomedical sciences, due to their biological role in signaling pathways and induction of cell damage at low and high concentrations, respectively. Detection of lipid peroxidation with sensing probes such as some BODIPY dyes has now wide application in studies using fluorescent microplate readers, flow cytometry, and fluorescence microscopy. Two phenylbutadiene derivatives of BODIPY are commonly used as peroxidation probes, non-oxidized probes and oxidized products giving red and green fluorescence, respectively.

Pseudouridine as a novel biomarker in prostate cancer.

Epitranscriptomic analysis has recently led to the profiling of modified nucleosides in cancer cell biological matrices, helping to elucidate their functional roles in cancer and reigniting interest in exploring their use as potential markers of cancer development and progression. Pseudouridine, one of the most well-known and the most abundant of the RNA nucleotide modifications, is the C5-glycoside isomer of uridine and its distinctive physiochemical properties allows it to perform many essential functions. Pseudouridine functionally (a) confers rigidity to local RNA structure by enhancing RNA stacking, engaging in a cooperative effect on neighboring nucleosides that overall contributes to RNA stabilization (b) refines the structure of tRNAs, which influences their decoding activity (c) facilitates the accuracy of decoding and proofreading during translation and efficiency of peptide bond formation, thus collectively improving the fidelity of protein biosynthesis and (e) dynamically regulates mRNA coding and translation.

Fluorescent redox-dependent labeling of lipid droplets in cultured cells by reduced phenazine methosulfate.

Natural and synthetic phenazines are widely used in biomedical sciences. In dehydrogenase histochemistry, phenazine methosulfate (PMS) is applied as a redox reagent for coupling reduced coenzymes to the reduction of tetrazolium salts into colored formazans. PMS is also currently used for cytotoxicity and viability assays of cell cultures using sulfonated tetrazoliums.

Predictive value of pseudouridine in prostate cancer.

Background: Recent studies have shown that certain small nucleolar RNAs (H/ACA snoRNAs) and the protein dyskerin (DKC1) are upregulated in prostate cancer and are thought to contribute to progression of disease. These components convert uridine to pseudouridine (abbreviated ψ), a type of post-transcriptional modification of RNA. Given the increased abundance of H/ACA snoRNAs and expression of DKC1 in prostate carcinomas, and because whole-body turnover of RNA increases in support of rapidly-growing cancer cells, we examined the value of pseudouridine as a biomarker for prostate cancer.

Photothermal effect by 808-nm laser irradiation of melanin: a proof-of-concept study of photothermal therapy using B16-F10 melanotic melanoma growing in BALB/c mice.

The photothermal effect is undergoing great interest due to advances in new photosensitizing materials and better-suited light sources, but studies are frequently hampered by the need to employ exogenous photothermal agents and expensive irradiation devices. Here we present a simple strategy based on direct NIR irradiation of the melanin pigment with a commercial 808-nm laser pointer. Proof-of-concept studies showed efficient photothermal effects on melanin and After NIR irradiation, BALB/c mice bearing B16-F10 melanotic melanoma tumors revealed severe histopathological damage and massive necrosis in melanin-containing tumor tissue, while surrounding healthy tissues showed no damage.

Inflammation and Prostate Cancer.

Chronic inflammation resulting from infections, altered metabolism, inflammatory diseases or other environmental factors can be a major contributor to the development of several types of cancer. In fact around 20% of all cancers are linked to some form of inflammation. Evidence gathered from genetic, epidemiological and molecular pathological studies suggest that inflammation plays a crucial role at various stages of prostatic carcinogenesis and tumor progression.

Intratumor heterogeneity in prostate cancer.

Prostate cancer (PCa) has long been thought of as a disease with a heterogeneous phenotype. It can manifest in men as benign growths that can be safely watched or as more aggressive malignancies that can prove fatal. Recent investigations at the genomic, histopathological and molecular levels have identified tumor heterogeneity, the phenomenon of individual tumor cells presenting distinct genomic and phenotypic characteristics, as one of the most confounding and complex factors underlying PCa diagnosis, prognosis, and treatment.

NIR laser pointer for in vivo photothermal therapy of murine LM3 tumor using intratumoral China ink as a photothermal agent.

The photothermal effect is one of the most promising photonic procedures currently under development to successfully treat several clinical disorders, none the least some kinds of cancer. At present, this field is undergoing a renewed interest due to advances in both photothermal materials and better-suited light sources. However, scientific studies in this area are sometimes hampered by the relative unavailability of state-of-art materials or the complexity of setting up a dedicated optical facility.

Tetrazolium salts and formazan products in Cell Biology: Viability assessment, fluorescence imaging, and labeling perspectives.

For many years various tetrazolium salts and their formazan products have been employed in histochemistry and for assessing cell viability. For the latter application, the most widely used are 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), and 5-cyano-2,3-di-(p-tolyl)-tetrazolium chloride (CTC) for viability assays of eukaryotic cells and bacteria, respectively. In these cases, the nicotinamide-adenine-dinucleotide (NAD(P)H) coenzyme and dehydrogenases from metabolically active cells reduce tetrazolium salts to strongly colored and lipophilic formazan products, which are then quantified by absorbance (MTT) or fluorescence (CTC).

Improved selectivity and cytotoxic effects of irinotecan via liposomal delivery: A comparative study on Hs68 and HeLa cells.

Irinotecan (CPT-11) is an effective chemotherapeutic agent widely used to treat different cancers. Otherwise, the liposomal delivery of anti-tumor agents has been shown to be a promising strategy. The aim of this study has been to analyze the effect of liposomal CPT-11 (CPT-11lip) on two human cell lines (Hs68 and HeLa) to establish the suitability of this CPT-11 nanocarrier.

Induction of Neuroendocrine Differentiation in Prostate Cancer Cells by Dovitinib (TKI-258) and its Therapeutic Implications.

Prostate cancer (PCa) remains the second-leading cause of cancer-related deaths in American men with an estimated mortality of more than 26,000 in 2016 alone. Aggressive and metastatic tumors are treated with androgen deprivation therapies (ADT); however, the tumors acquire resistance and develop into lethal castration resistant prostate cancer (CRPC). With the advent of better therapeutics, the incidences of a more aggressive neuroendocrine prostate cancer (NEPC) variant continue to emerge.

Photodynamic Synergistic Effect of Pheophorbide a and Doxorubicin in Combined Treatment against Tumoral Cells.

A combination of therapies to treat cancer malignancies is at the forefront of research with the aim to reduce drug doses (ultimately side effects) and diminish the possibility of resistance emergence given the multitarget strategy. With this goal in mind, in the present study, we report the combination between the chemotherapeutic drug doxorubicin (DOXO) and the photosensitizing agent pheophorbide a (PhA) to inactivate HeLa cells. Photophysical studies revealed that DOXO can quench the excited states of PhA, detracting from its photosensitizing ability.

Combination effect of therapies targeting the PI3K- and AR-signaling pathways in prostate cancer.

Several promising targeted-therapeutics for prostate cancer (PCa), primarily affecting the androgen receptor (AR) and the PI3K/AKT/mTOR-pathway, are in various phases of development. However, despite promise, single-agent inhibitors targeting the two pathways have not shown long-term benefits, perhaps due to a complex compensatory cross talk that exists between the two pathways. Combination therapy has thus been proposed to maximize benefit.

Establishing the subcellular localization of photodynamically-induced ROS using 3,3'-diaminobenzidine: A methodological proposal, with a proof-of-concept demonstration.

The critical involvement of reactive oxygen species (ROS) in both physiological and pathological processes in cell biology makes their detection and assessment a fundamental topic in biomedical research. Established methodologies to study ROS in cell biology take advantage of oxidation reactions between the ROS and a reduced probe. After reacting the probe reveals the presence of ROS either by the appearance of colour (chromogenic reaction) or fluorescence (fluorogenic reaction).

Identification of a small-molecule ligand that activates the neuropeptide receptor GPR171 and increases food intake.

Several neuropeptide systems in the hypothalamus, including neuropeptide Y and agouti-related protein (AgRP), control food intake. Peptides derived from proSAAS, a precursor implicated in the regulation of body weight, also control food intake. GPR171 is a heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptor (GPCR) for BigLEN (b-LEN), a peptide derived from proSAAS.

Poly(D, L-lactide-co-glycolide) nanoparticles as delivery agents for photodynamic therapy: enhancing singlet oxygen release and photototoxicity by surface PEG coating.

Poly(D, L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) are being considered as nanodelivery systems for photodynamic therapy. The physico-chemical and biological aspects of their use remain largely unknown. Herein we report the results of a study of PLGA NPs for the delivery of the model hydrophobic photosensitizer ZnTPP to HeLa cells.