On the dynamics of the adenylate energy system: homeorhesis vs homeostasis.

Biochemical energy is the fundamental element that maintains both the adequate turnover of the biomolecular structures and the functional metabolic viability of unicellular organisms. The levels of ATP, ADP and AMP reflect roughly the energetic status of the cell, and a precise ratio relating them was proposed by Atkinson as the adenylate energy charge (AEC). Under growth-phase conditions, cells maintain the AEC within narrow physiological values, despite extremely large fluctuations in the adenine nucleotides concentration. Intensive experimental studies have shown that these AEC values are preserved in a wide variety of organisms, both eukaryotes and prokaryotes. Here, to understand some of the functional elements involved in the cellular energy status, we present a computational model conformed by some key essential parts of the adenylate energy system. Specifically, we have considered (I) the main synthesis process of ATP from ADP, (II) the main catalyzed phosphotransfer reaction for interconversion of ATP, ADP and AMP, (III) the enzymatic hydrolysis of ATP yielding ADP, and (IV) the enzymatic hydrolysis of ATP providing AMP. This leads to a dynamic metabolic model (with the form of a delayed differential system) in which the enzymatic rate equations and all the physiological kinetic parameters have been explicitly considered and experimentally tested in vitro. Our central hypothesis is that cells are characterized by changing energy dynamics (homeorhesis). The results show that the AEC presents stable transitions between steady states and periodic oscillations and, in agreement with experimental data these oscillations range within the narrow AEC window. Furthermore, the model shows sustained oscillations in the Gibbs free energy and in the total nucleotide pool. The present study provides a step forward towards the understanding of the fundamental principles and quantitative laws governing the adenylate energy system, which is a fundamental element for unveiling the dynamics of cellular life

Reactive oxygen species and male reproductive hormones

Reports of the increasing incidence of male infertility paired with decreasing semen quality have triggered studies on the effects of lifestyle and environmental factors on the male reproductive potential. There are numerous exogenous and endogenous factors that are able to induce excessive production of reactive oxygen species (ROS) beyond that of cellular antioxidant capacity, thus causing oxidative stress. In turn, oxidative stress negatively affects male reproductive functions and may induce infertility either directly or indirectly by affecting the hypothalamus-pituitary-gonadal (HPG) axis and/or disrupting its crosstalk with other hormonal axes. This review discusses the important exogenous and endogenous factors leading to the generation of ROS in different parts of the male reproductive tract. It also highlights the negative impact of oxidative stress on the regulation and cross-talk between the reproductive hormones. It further describes the mechanism of ROS-induced derangement of male reproductive hormonal profiles that could ultimately lead to male infertility. An understanding of the disruptive effects of ROS on male reproductive hormones would encourage further investigations directed towards the prevention of ROS-mediated hormonal imbalances, which in turn could help in the management of male infertility

Gold Nanocages as Effective Photothermal Transducers in Killing Highly Tumorigenic Cancer Cells

Numerous gold nanostructures have the potential for photothermal therapy in cancers. Here, gold nanocages and gold nanoshells are synthesized, the sizes of which are fine-tuned for a response at 750 nm wavelength. Their photothermal therapeutic efficiency is compared at gold concentration of 100 lg mL(-1) using a near-infrared laser (750 nm). The biocompatibility for varying concentrations of gold (1 to 100 lg mL(-1)) is performed in a normal cell line and laser-mediated cell cytotoxicity for varying time intervals (7.5 and 10 min) is carried out in breast cancer cells. This study shows that when analyzed under similar conditions, the gold nanocages show better biocompatibility and are more efficient in near-infrared absorption and photothermal conversion in comparison with conventional gold nanoshells. When subjected to photothermal laser ablation of breast cancer cell line for 7.5 min and 10 min, the nanocages are able to induce 62.92 +/- 3.25% and 96.41 +/- 3.04% reduction in cell viability, respectively, in comparison to nanoshells, in which a 43.35 +/- 1.91% and 79.89 +/- 4.74% reduction in cell viability is observed. The current study shows that the gold nanocages can outperform gold nanoshells and effectively kill cancer cells without any significant cytotoxic effect on normal cells

Biocompatible Amphiphilic Pentablock Copolymeric Nanoparticles for Anti-Cancer Drug Delivery

A pentablock copolymer of Poly(Lactide-co-Glycolide) and Pluronic F68 was synthesized using ring-opening polymerization and characterized by NMR and FTIR for confirming the structure of the block copolymer. TG-DTA studies showed PLGA:Pluronic ratio to be 4:1. As the PLGA-PEO-PPO-PEO-PLGA Pentablock Copolymer (PPPC) prepared is amphiphilic, its Critical Vesicular Concentration, was measured, which was lower at 37 degrees C than at 25 degrees C, which could provide better stability to the system at physiological temperature. The nanoparticles of PPPC vary in topographyand range from 150 to 500 nm in size, according to the synthesis route used viz Emulsion Solvent Evaporation and simple dialysis. Pentablock copolymer nanoparticles were found to entrap about 84% of hydrophobic drug, docetaxel. Drug release profile of docetaxel showed about 50% release in first 2 hours at pH 4.6 and about 80% docetaxel was released at pH 7.4, at the end of 2 days. The PPPC nanoparticles was found to be biocompatible to L929 cell lines up to 1 mg/ml concentration. Preliminary in vitro cytotoxic effect of docetaxel loaded PPPC nanoparticles against four different cancer cell lines showed 50% inhibitory concentration of 6 nM in A431 (Squamous cell carcinoma), 250 nM in HeLa (Cervical carcinoma), 800 nM in PC3 (Prostate carcinoma) and 1 mu M in KB (Epidermoid carcinoma) cells

Gold laced bio-macromolecules for theranostic application

Gold nanostructures are promising entities for various biomedical applications, due to their promising physical and optical properties. They can be tailored in different sizes and shapes to play vital roles for photothermal therapy, Biosensing, in vivo X-ray/CT contrast etc. Many biomacromolecules have been used for chemical reduction of ionic gold into zero-valent metallic nanoparticles of specific shape/size followed by stabilizing them for long term utilization. This review will sum up a range of biomacromolecules including Alginate, Agarose, Starch, Carragenan, Cellulose, Chitin, Chitosan, Collagen, Cyclodextrins, Chondrotin Sulfate, Dextran Sulfate, Fucoidan, Gelatin, Guar Gum and Hyaluronic Acid, whose functionalities have been explored in combination with gold nanoparticles for various biomedical applications. (C) 2017 Elsevier B.V. All rights reserved

Multifunctional gold coated thermo-sensitive liposomes for multimodal imaging and photothermal therapy of breast cancer cells

Plasmon resonant gold nanoparticles of various sizes and shapes have been extensively researched for their applications in imaging, drug delivery and photothermal therapy (PTT). However, their ability to degrade after performing the required function is essential for their application in healthcare. When combined with biodegradable liposomes, they appear to have better degradation capabilities. They degrade into smaller particles of around 5 nm that are eligible candidates for renal clearance. Distearoyl phosphatidyl choline : cholesterol (DSPC : CHOL, 8 : 2 wt%) liposomes have been synthesized and coated with gold by in situ reduction of chloro-auric acid. These particles of size 150-200 nm are analyzed for their stability, degradation capacity, model drug-release profile, biocompatibility and photothermal effects on cancer cells. It is observed that when these particles are subjected to low power continuous wave near infra-red (NIR) laser for more than 10 min, they degrade into small gold nanoparticles of size 5 nm. Also, the gold coated liposomes appear to have excellent biocompatibility and high efficiency to kill cancer cells through photothermal transduction. These novel materials are also useful in imaging using specific NIR dyes, thus exhibiting multifunctional properties for theranostics of cancer

NIR triggered liposome gold nanoparticles entrapping curcumin as in situ adjuvant for photothermal treatment of skin cancer

We report the synthesis of a biodegradable liposome gold nanoparticles for curcumin (Au-Lipos Cur NPs) delivery. This entrapped curcumin served as an in situ adjuvant for photothermal therapy. Curcumin was loaded in Au-Lipos NPs with an encapsulation efficiency of similar to 70%. The gold coating enabled the NPs to specifically absorb NIR light (780 nm) by virtue of Surface Plasmon Resonance (SPR) and this light energy was converted to heat. The generated heat destabilized the liposomal core enhancing the release of encapsulated curcumin. Photothermal transduction efficacy of Au-Lipos NPs (loaded with curcumin) showed a significant temperature rise upon laser irradiation causing irreversible cellular damage. In vitro photothermal effect and intracellular uptake was evaluated in B16 F10 (melanoma) cell line. Au-Lipos Cur NPs showed significantly enhanced uptake when compared with free curcumin. Enhancement in cancer cell cytotoxicity was observed in Au-Lipos Cur NPs treated group upon laser irradiation owing to curcumin. Our findings indicate that curcumin could serve as a potential in situ adjuvant for photothermal therapy of melanoma. (C) 2017 Elsevier B.V. All rights reserved