Lower critical solution temperature versus volume phase transition temperature in thermoresponsive drug delivery systems

One of the most subtle problem in the characterization of thermoresponsive polymers is the evaluation of the relationship between the lower critical solution temperature (LCST) of the linear polymer and the volume phase transition temperature (VPTT) of the corresponding hydrogel. Here, the LCST and the onset temperature of linear poly(N-isopropy- lacrylamide-co-N-hydroxymethyl acrylamide) has been determined under pseudo-physiological conditions by cloud point (CP) measurements and by microcalorimetric analysis. The LCSTs, as well as the onset temperatures, determined by the CP method, decrease with increasing the concentration of the polymer solution. On the contrary, microcalorimetric analyses give almost the same values for LCSTs and the onset temperatures regardless of polymer concentration. The VPTT of the hydrogel, determined by the blue dextran method, was found to be closely similar to the LCST of the concentrated polymer solution (10%, w/v), determined by the CP method. In fact, the hydrogel could be considered as a concentrated polymer solution whose concentration could be related to the amount of water retained by the hydrogel. Hydrogel microspheres have been also reported to release diclofenac, a drug model system, in a pulsating way at temperatures slightly below and above the VPTT

3D Neuron Cluster Organoid – Artificial Intelligence using High-Speed Organic Neural Network

Since the beginning of time, Humanity has relied on the careful analysis of nature to better understand the world around us. The same can be said of our current Bio-Technical Research Environment and our feeble Artificial Intelligence endeavors. We have always closely studied the biological world in order to find the best solutions and further develop technologies to help push the boundaries of medicine. In this regard, our Quantum Medicine department proposes the creation of a 3D human neuron cluster organoid that can be connected to and controlled using outside stimuli that rely on the visible light spectrum to encode and decode information directly. This process would imply the development of technologies for photonic encryption and decryption as well as low-current transformers to aid in neuron signal decoding and recoding. The scope of the project is to start using the neuron organoid as a biological neural net and observe the speed at which it learns and outputs solutions compared to traditional software Neural Networks. Our goal is to try and figure out the possibility of creating faster learning models and testing the actual speed of their learning capability, which would bring us closer to understanding the way information is structured and shared between different parts of the brain. In turn, this has the potential to yield a new type of artificial intelligence biohardware based on low power consumption that could aid in the future development of smart biotech and nano-biorobotics with fast AI systems. In conclusion, the aim of this project is to prove the programmability and learning capabilities of a 3-dimensional bio-neural-network organoid by using different data transmission mediums and new algorithms. Our common goal is the advancement of biomedical research to aid in humanity’s medical and otherworldly endeavors and be the perfect launch platform for generations to come

Composite Hydrogels with Embedded Silver Nanoparticles and Ibuprofen as Wound Dressing

The wound healing process is often slowed down as a result of complications from bacterial infections and inflammatory reactions. Therefore, it is necessary to develop dressings with fast antibacterial and anti-inflammatory activity that shorten the wound healing period by promoting cell migration and proliferation. Chitosan (CS)-based hydrogels have been widely studied for their antibacterial and wound healing capabilities. Herein, we developed a composite hydrogel based on CS and PVA embedding silver nanoparticles (AgNPs) with antibacterial properties and ibuprofen (Ib) as an anti-inflammatory agent. The hydrogel prepared by double physical cross-linking, with oxalic acid and by freeze–thawing, loaded with 0.225 wt.% AgNPs and 0.264 wt.% Ib, displayed good mechanical properties (compressive modulus = 132 kPa), a high swelling degree and sustained drug delivery (in simulated skin conditions). Moreover, the hydrogel showed strong antibacterial activity against S. aureus and K. pneumoniae due to the embedded AgNPs. In vivo, this hydrogel accelerated the wound regeneration process through the enhanced expression of TNF alpha IP8, by activating downstream cascades and supporting the healing process of inflammation; Cox2, which enhances the migration and proliferation of cells involved in re-epithelization and angiogenesis; MHCII, which promotes immune cooperation between local cells, eliminating dead tissue and controlling infection; the intense expression of Col I as a major marker in the tissue granulation process; and αSMA, which marks the presence of myofibroblasts involved in wound closure and indicates ongoing re-epithelization. The results reveal the potential healing effect of CS/PVA/AgNPs/Ib hydrogels and suggest their potential use as wound dressings

The therapeutic effect of mineral water from spring 3 in Baile Tusnad in experimental alcoholic liver disease in rats – an electron microscopic study

The aim of this study was to investigate by transmission electron microscopy the changes occurring in rat hepatocytes following administration of ethyl alcohol for 70 days, as well as to evaluate the effect of mineral water from spring 3 in Baile Tusnad balneoclimatic resort administered for 30 days after completion of ethyl alcohol administration. After 70 days of ethyl alcohol administration, lipid loading in hepatocytes and a reduction of the rough endoplasmic reticulum were observed. The smooth endoplasmic reticulum was found to be much more abundant and in some hepatocytes that contained high lipid amounts, mitochondria had rarefied matrix and cristae. At 30 days from completion of ethyl alcohol administration, the rats that drank tap water showed progressively decreasing lipid loading. Also, the smooth endoplasmic reticulum was less abundant, while the rough endoplasmic reticulum was more abundant than on day 70 of the experiment. The rats that drank mineral water from spring 3 compared to those that drank tap water over the last 30 days of the experiment had lower hepatocyte lipid loading and the rough endoplasmic reticulum was much more abundant. These ultrastructural differences in the degree of lipid loading and the ratio between the smooth and rough endoplasmic reticulum are due to the beneficial effect of mineral water from spring 3 in Baile Tusnad

Thermosensitive Poloxamer-graft-Carboxymethyl Pullulan: A Potential Injectable Hydrogel for Drug Delivery

A thermosensitive copolymer composed of amphiphilic triblock copolymer, poloxamer 407, grafted on hydrophilic pullulan with pendant carboxymethyl groups (CMP) was prepared and characterized. The structure of the new copolymer was assessed by Fourier transform infrared (FT-IR) and 1H nuclear magnetic resonance (1H NMR) spectroscopy. The content of the poloxamer in the grafted copolymer was 83.8% (w/w). The effect of the copolymer concentration on the gelation behavior was analyzed by the vertical method and rheological tests; the gel phase of the copolymer occurred at a lower concentration (11%, w/v) as compared with poloxamer (18%, w/v). The starting gelation time under the simulated physiological conditions (phosphate buffer with a pH of 7.4, at 37 °C) was sensitive on the rest temperature before the test, this being 990 s and 280 s after 24 h rest at 4 °C and 20 °C, respectively. The rheological tests evidenced a high elasticity and excellent ability of the copolymer to recover the initial structure after the removal of the applied force or external stimuli. Moreover, the hydrogel has proved a sustained release of amoxicillin (taken as a model drug) over 168 h. Taken together, the results clearly indicate that this copolymer can be used as an injectable hydrogel

Interrogating Epigenome toward Personalized Approach in Cutaneous Melanoma

Epigenetic alterations have emerged as essential contributors in the pathogenesis of various human diseases, including cutaneous melanoma (CM). Unlike genetic changes, epigenetic modifications are highly dynamic and reversible and thus easy to regulate. Here, we present a comprehensive review of the latest research findings on the role of genetic and epigenetic alterations in CM initiation and development. We believe that a better understanding of how aberrant DNA methylation and histone modifications, along with other molecular processes, affect the genesis and clinical behavior of CM can provide the clinical management of this disease a wide range of diagnostic and prognostic biomarkers, as well as potential therapeutic targets that can be used to prevent or abrogate drug resistance. We will also approach the modalities by which these epigenetic alterations can be used to customize the therapeutic algorithms in CM, the current status of epi-therapies, and the preliminary results of epigenetic and traditional combinatorial pharmacological approaches in this fatal disease

Proteomic Technology “Lens” for Epithelial-Mesenchymal Transition Process Identification in Oncology

The epithelial-mesenchymal transition (EMT) is a complex transformation process that induces local and distant progression of many malignant tumours. Due to its complex array of proteins that are dynamically over-/underexpressed during this process, proteomic technologies gained their place in the EMT research in the last years. Proteomics has identified new molecular pathways of this process and brought important insights to develop new therapy targets. Various proteomic tools and multiple combinations were developed in this area. Out of the proteomic technology armentarium, mass spectrometry and array technologies are the most used approaches. The main characteristics of the proteomic technology used in this domain are high throughput and detection of minute concentration in small samples. We present herein, using various proteomic technologies, the identification in cancer cell lines and in tumour tissue EMT-related proteins, proteins that are involved in the activation of different cellular pathways. Proteomics has brought besides standard EMT markers (e.g., cell-cell adhesion proteins and transcription factors) other future potential markers for improving diagnosis, monitoring evolution, and developing new therapy targets. Future will increase the proteomic role in clinical investigation and validation of EMT-related biomarkers

Epitranscriptomic Signatures in lncRNAs and Their Possible Roles in Cancer

In contrast to the amazing exponential growth in knowledge related to long non-coding RNAs (lncRNAs) involved in cell homeostasis or dysregulated pathological states, little is known so far about the links between the chemical modifications occurring in lncRNAs and their function. Generally, ncRNAs are post-transcriptional regulators of gene expression, but RNA modifications occurring in lncRNAs generate an additional layer of gene expression control. Chemical modifications that have been reported in correlation with lncRNAs include m6A, m5C and pseudouridylation. Up to date, several chemically modified long non-coding transcripts have been identified and associated with different pathologies, including cancers. This review presents the current level of knowledge on the most studied cancer-related lncRNAs, such as the metastasis associated lung adenocarcinoma transcript 1 (MALAT1), the Hox transcript antisense intergenic RNA (HOTAIR), or the X-inactive specific transcript (XIST), as well as more recently discovered forms, and their potential roles in different types of cancer. Understanding how these RNA modifications occur, and the correlation between lncRNA changes in structure and function, may open up new therapeutic possibilities in cancer

Pullulan/Poly(vinyl alcohol) Hydrogels Loaded with Calendula officinalis Extract: Design and In Vitro Evaluation for Wound Healing Applications

The therapeutic efficiency of plant extracts has been limited by their poor pharmaceutical availability. Hydrogels have promising potential to be applied as wound dressings due to their high capacity to absorb exudates and their enhanced performance in loading and releasing plant extracts. In this work, pullulan/poly (vinyl alcohol) (P/PVA) hydrogels were first prepared using an eco-friendly method based on both a covalent and physical cross-linking approach. Then, the hydrogels were loaded with the hydroalcoholic extract of Calendula officinalis by a simple post-loading immersion method. Different loading capacities were investigated in terms of the physico-chemical properties, chemical composition, mechanical properties, and water absorption. The hydrogels exhibited high loading efficiency due to the hydrogen bonding interactions between polymer and extract. The water retention capacity as well as the mechanical properties decreased with the increase in the extract amount in hydrogel. However, higher amounts of extract in the hydrogel improved the bioadhesiveness. The release of extract from hydrogels was controlled by the Fickian diffusion mechanism. Extract-loaded hydrogels expressed high antioxidant activity, reaching 70% DPPH radical scavenging after 15 min immersion in buffer solution at pH 5.5. Additionally, loaded hydrogels showed a high antibacterial activity against Gram-positive and Gram-negative bacteria and were non-cytotoxic against HDFa cells