Formulation and Comprehensive Evaluation of Biohybrid Hydrogel Membranes Containing Doxycycline or Silver Nanoparticles.

Complicated wounds often require specialized medical treatments, and hydrogels have emerged as a popular choice for wound dressings in such cases due to their unique properties and the ability to incorporate and release therapeutic agents. Our focus was to develop and characterize a new optimized formula for biohybrid hydrogel membranes, which combine natural and synthetic polymers, bioactive natural compounds, like collagen and hyaluronic acid, and pharmacologically active substances (doxycycline or npAg). Dynamic (oscillatory) rheometry confirmed the strong gel-like properties of the obtained hydrogel membranes. Samples containing low-dose DOXY showed a swelling index of 285.68 ± 6.99%, a degradation rate of 71.6 ± 0.91% at 20 h, and achieved a cumulative drug release of approximately 90% at pH 7.4 and 80% at pH 8.3 within 12 h. The addition of npAg influenced the physical properties of the hydrogel membranes. Furthermore, the samples containing DOXY demonstrated exceptional antimicrobial efficacy against seven selected bacterial strains commonly associated with wound infections and complications. Biocompatibility assessments revealed that the samples exhibited over 80% cell viability. However, the addition of smaller-sized nanoparticles led to decreased cellular viability. The obtained biohybrid hydrogel membranes show favorable properties that render them suitable for application as wound dressings.

Behaviour testing in two different knockout mouse strains related to chronic inflammation and oxidative stress.

CD36, a fatty acid translocator and NRF2, a transcription factor, are two important players in inflammation and oxidative stress, including in the central nervous system. Both were associated with neurodegeneration as tilting arms of a balance: while activation of CD36 participates in neuroinflammation, activation of NRF2 seems to protect against oxidative stress and neuroinflammation. This study aimed to establish whether tilting the balance one way or the other, by knocking out either of them (NRF2-/- or CD36-/-), would show that one holds higher weight over the other in the cognitive behaviour of mice. We tested both young and old knockout animals in a long-term testing protocol (over one month), using the 8-arm radial maze,. Young NRF2-/- mice exhibited a sustained anxious-like behaviour, which was not recapitulated in old mice nor CD36 -/- mice of either age. Neither knockout strain exhibited cognitive alterations, although CD36 -/- mice showed some improvement over WT littermates. In conclusion, NRF2-/- seems to affect behaviour of mice early in life, and could be considered a vulnerability factor for neurocognition, while CD36 impact on cognitive protection of the aging brain requires more investigation.

Exploring the Impact of Alginate-PVA Ratio and the Addition of Bioactive Substances on the Performance of Hybrid Hydrogel Membranes as Potential Wound Dressings.

Healthcare professionals face an ongoing challenge in managing both acute and chronic wounds, given the potential impact on patients' quality of life and the limited availability of expensive treatment options. Hydrogel wound dressings offer a promising solution for effective wound care due to their affordability, ease of use, and ability to incorporate bioactive substances that enhance the wound healing process. Our study aimed to develop and evaluate hybrid hydrogel membranes enriched with bioactive components such as collagen and hyaluronic acid. We utilized both natural and synthetic polymers and employed a scalable, non-toxic, and environmentally friendly production process. We conducted extensive testing, including an in vitro assessment of moisture content, moisture uptake, swelling rate, gel fraction, biodegradation, water vapor transmission rate, protein denaturation, and protein adsorption. We evaluated the biocompatibility of the hydrogel membranes through cellular assays and performed instrumental tests using scanning electron microscopy and rheological analysis. Our findings demonstrate that the biohybrid hydrogel membranes exhibit cumulative properties with a favorable swelling ratio, optimal permeation properties, and good biocompatibility, all achieved with minimal concentrations of bioactive agents.

Assessing Polysaccharides/Aloe Vera-Based Hydrogels for Tumor Spheroid Formation.

In vitro tumor spheroids have proven to be useful 3D tumor culture models for drug testing, and determining the molecular mechanism of tumor progression and cellular interactions. Therefore, there is a continuous search for their industrial scalability and routine preparation. Considering that hydrogels are promising systems that can favor the formation of tumor spheroids, our study aimed to investigate and develop less expensive and easy-to-use amorphous and crosslinked hydrogels, based on natural compounds such as sodium alginate (NaAlg), aloe vera (AV) gel powder, and chitosan (CS) for tumor spheroid formation. The ability of the developed hydrogels to be a potential spheroid-forming system was evaluated using MDA-MB-231 and U87MG cancer cells. Spheroid abilities were influenced by pH, viscosity, and crosslinking of the hydrogel. Addition of either AV or chitosan to sodium alginate increased the viscosity at pH 5, resulting in amorphous hydrogels with a strong gel texture, as shown by rheologic analysis. Only the chitosan-based gel allowed formation of spheroids at pH 5. Among the variants of AV-based amorphous hydrogels tested, only hydrogels at pH 12 and with low viscosity promoted the formation of spheroids. The crosslinked NaAlg/AV, NaAlg/AV/glucose, and NaAlg/CS hydrogel variants favored more efficient spheroid formation. Additional studies would be needed to use AV in other physical forms and other formulations of hydrogels, as the current study is an initiation, in evaluating the potential use of AV gel in tumor spheroid formation systems.

Vertical Graphene-Based Biosensor for Tumor Cell Dielectric Signature Evaluation.

The selective and rapid detection of tumor cells is of critical consequence for the theragnostic field of tumorigenesis; conventional methods, such as histopathological diagnostic methods, often require a long analysis time, excessive analytical costs, complex operations, qualified personnel and deliver many false-positive results. We are considering a new approach of an electrochemical biosensor based on graphene, which is evidenced to be a revolutionary nanomaterial enabling the specific and selective capture of tumor cells. In this paper, we report a biosensor fabricated by growing vertically aligned graphene nanosheets on the conductive surface of interdigitated electrodes which is functionalized with anti-EpCAM antibodies. The dielectric signature of the three types of tumor cells is determined by correlating the values from the Nyquist and Bode diagram: charge transfer resistance, electrical double layer capacity, Debye length, characteristic relaxation times of mobile charges, diffusion/adsorption coefficients, and variation in the electrical permittivity complex and of the phase shift with frequency. These characteristics are strongly dependent on the type of membrane molecules and the electromagnetic resonance frequency. We were able to use the fabricated sensor to differentiate between three types of tumor cell lines, HT-29, SW403 and MCF-7, by dielectric signature. The proposed evaluation method showed the permittivity at 1 MHz to be 3.63 nF for SW403 cells, 4.97 nF for HT 29 cells and 6.9 nF for MCF-7 cells.

New Amorphous Hydrogels with Proliferative Properties as Potential Tools in Wound Healing.

The study and discovery of bioactive compounds and new formulations as potential tools for promoting the repair of dermoepidermal tissue in wound healing is of continuing interest. We have developed a new formulation of amorphous hydrogel based on sodium alginate (NaAlg); type I collagen, isolated by the authors from silver carp tails (COL); glycerol (Gli); Aloe vera gel powder (AV); and silver nanoparticles obtained by green synthesis with aqueous Cinnamomum verum extract (AgNPs@CIN) and vitamin C, respectively. The gel texture of the amorphous hydrogels was achieved by the addition of Aloe vera, demonstrated by a rheological analysis. The evaluations of the cytotoxicity and cell proliferation capacity of the experimental amorphous hydrogels were performed against human foreskin fibroblast Hs27 cells (CRL-1634-ATCC). The developed gel formulations did not show a cytotoxic effect. The hydrogel variant containing AgNPs@CIN in a concentration of 8 µg Ag/gel formulation and hydrogel variant with vitamin C had proliferative activity. In addition, the antibacterial activity of the hydrogels was evaluated against S. aureus ATCC 6538, Ps. aeruginosa ATCC 27853, and E. coli ATCC 25922. The results demonstrated that the gel variant based on AgNPs@CIN in a concentration of 95 µg Ag/gel formulation and the hydrogel based on vitamin C show antibacterial activity. Therefore, the developed hydrogels with AgNPs@CIN and vitamin C could be promising alternatives in wound healing.

Low-Concentrations of Fatty Acids Induce an Early Increase in IL-8 Levels in Normal Human Astrocytes.

Fatty acids (FAs) have been shown to exhibit a pro-inflammatory response in various cell types, but astrocytes have been mostly overlooked. FAs, both saturated and unsaturated, have previously been shown to induce pro-inflammatory responses in astrocytes at high concentrations of hundreds of µg/mL. SSO (Sulfo-N-succinimidyl Oleate sodium), an inhibitor of FA translocase CD36, has been shown to prevent inflammation in the mouse brain by acting on local microglia and infiltrating monocytes. Our hypothesis was that SSO treatment would also impact astrocyte pro-inflammatory response to FA. In order to verify our assumption, we evaluated the expression of pro- and anti-inflammatory cytokines in normal human astrocyte cell culture pre-treated (or not) with SSO, and then exposed to low concentrations of both saturated (palmitic acid) and unsaturated (oleic acid) FAs. As a positive control for astrocyte inflammation, we used fibrillary amyloid. Neither Aß 1-42 nor FAs induced CD36 protein expression in human astrocytes in cell culture At low concentrations, both types of FAs induced IL-8 protein secretion, and this effect was specifically inhibited by SSO pre-treatment. In conclusion, low concentrations of oleic acid are able to induce an early increase in IL-8 expression in normal human astrocytes, which is specifically downregulated by SSO.

Friends with Benefits: Chemokines, Glioblastoma-Associated Microglia/Macrophages, and Tumor Microenvironment.

Glioma is the most common primary intracranial tumor and has the greatest prevalence of all brain tumors. Treatment resistance and tumor recurrence in GBM are mostly explained by considerable alterations within the tumor microenvironment, as well as extraordinary cellular and molecular heterogeneity. Soluble factors, extracellular matrix components, tissue-resident cell types, resident or newly recruited immune cells together make up the GBM microenvironment. Regardless of many immune cells, a profound state of tumor immunosuppression is supported and developed, posing a considerable hurdle to cancer cells' immune-mediated destruction. Several studies have suggested that various GBM subtypes present different modifications in their microenvironment, although the importance of the microenvironment in treatment response has yet to be determined. Understanding the microenvironment and how it changes after therapies is critical because it can influence the remaining invasive GSCs and lead to recurrence. This review article sheds light on the various components of the GBM microenvironment and their roles in tumoral development, as well as immune-related biological processes that support the interconnection/interrelationship between different cell types. Also, we summarize the current understanding of the modulation of soluble factors and highlight the dysregulated inflammatory chemokine/specific receptors cascades/networks and their significance in tumorigenesis, cancer-related inflammation, and metastasis.

Fatty Acids, CD36, Thrombospondin-1, and CD47 in Glioblastoma: Together and/or Separately?

Glioblastoma (GBM) is one of the most aggressive tumors of the central nervous system, characterized by a wide range of inter- and intratumor heterogeneity. Accumulation of fatty acids (FA) metabolites was associated with a low survival rate in high-grade glioma patients. The diversity of brain lipids, especially polyunsaturated fatty acids (PUFAs), is greater than in all other organs and several classes of proteins, such as FA transport proteins (FATPs), and FA translocases are considered principal candidates for PUFAs transport through BBB and delivery of PUFAs to brain cells. Among these, the CD36 FA translocase promotes long-chain FA uptake as well as oxidated lipoproteins. Moreover, CD36 binds and recognizes thrombospondin-1 (TSP-1), an extracellular matrix protein that was shown to play a multifaceted role in cancer as part of the tumor microenvironment. Effects on tumor cells are mediated by TSP-1 through the interaction with CD36 as well as CD47, a member of the immunoglobulin superfamily. TSP-1/CD47 interactions have an important role in the modulation of glioma cell invasion and angiogenesis in GBM. Separately, FA, the two membrane receptors CD36, CD47, and their joint ligand TSP-1 all play a part in GBM pathogenesis. The last research has put in light their interconnection/interrelationship in order to exert a cumulative effect in the modulation of the GBM molecular network.

A Fatty Acid Fraction Purified From Sea Buckthorn Seed Oil Has Regenerative Properties on Normal Skin Cells.

In recent years, natural product's research gained momentum, fueled by technological advancement and open availability of research data. To date, sea buckthorn (Hippophae rhamnoides L. [Elaeagnaceae]) plant parts, especially berries, are well characterized and repeatedly tested for antioxidant activity and regenerative properties, in various cell types and tissues. However, fatty acids (FA) have been less investigated in term of biological effects, although, they are important bioactive components of the sea buckthorn fruit and oil. The aim of our work was to determine whether sea buckthorn seed oil is a suitable source of FA with regenerative properties on normal skin cells. Using high-performance liquid chromatography (HPLC) and liquid chromatography - mass spectrometry (LC-MS), we purified and characterized four fractions enriched in saturated (palmitic) and non-saturated (linoleic, alfa-linolenic, oleic) FA, which were tested for cytotoxicity, cytokine and growth factor production, and regenerative effect on normal keratinocytes and skin fibroblasts. Evidence is presented that the palmitic acid enriched fraction was a suitable sea buckthorn seed oil derived product with cell proliferation properties on both skin cell types.

Natural Compounds With Antimicrobial and Antiviral Effect and Nanocarriers Used for Their Transportation.

Due to the increasing prevalence of life-threatening bacterial, fungal and viral infections and the ability of these human pathogens to develop resistance to current treatment strategies, there is a great need to find and develop new compunds to combat them. These molecules must have low toxicity, specific activity and high bioavailability. The most suitable compounds for this task are usually derived from natural sources (animal, plant or even microbial). In this review article, the latest and most promising natural compounds used to combat bacteria, filamentous fungi and viruses are presented and evaluated. These include plant extracts, essential oils, small antimicrobial peptides of animal origin, bacteriocins and various groups of plant compounds (triterpenoids; alkaloids; phenols; flavonoids) with antimicrobial and antiviral activity. Data are presented on the inhibitory activity of each natural antimicrobial substance and on the putative mechanism of action against bacterial and fungal strains. The results show that among the bioactive compounds studied, triterpenoids have significant inhibitory activity against coronaviruses, but flavonoids have also been shown to inhibit SARS-COV-2. The last chapter is devoted to nanocarriers used to improve stability, bioavailability, cellular uptake/internalization, pharmacokinetic profile and reduce toxicity of natural compunds. There are a number of nanocarriers such as liposomes, drug delivery microemulsion systems, nanocapsules, solid lipid nanoparticles, polymeric micelles, dendrimers, etc. However, some of the recent studies have focused on the incorporation of natural substances with antimicrobial/antiviral activity into polymeric nanoparticles, niosomes and silver nanoparticles (which have been shown to have intrinsic antimicrobial activity). The natural antimicrobials isolated from animals and microorganisms have been shown to have good inhibitory effect on a range of pathogens, however the plants remain the most prolific source. Even if the majority of the studies for the biological activity evaluation are in silico or in vitro, their internalization in the optimum nanocarriers represents the future of "green therapeutics" as shown by some of the recent work in the field.

The Physico-Chemical Properties and Exploratory Real-Time Cell Analysis of Hydroxyapatite Nanopowders Substituted with Ce, Mg, Sr, and Zn (0.5-5 at.%).

Cation-substituted hydroxyapatite (HA), standalone or as a composite (blended with polymers or metals), is currently regarded as a noteworthy candidate material for bone repair/regeneration either in the form of powders, porous scaffolds or coatings for endo-osseous dental and orthopaedic implants. As a response to the numerous contradictions reported in literature, this work presents, in one study, the physico-chemical properties and the cytocompatibility response of single cation-doped (Ce, Mg, Sr or Zn) HA nanopowders in a wide concentration range (0.5-5 at.%). The modification of composition, morphology, and structure was multiparametrically monitored via energy dispersive X-ray, X-ray photoelectron, Fourier-transform infrared and micro-Raman spectroscopy methods, as well as by transmission electron microscopy and X-ray diffraction. From a compositional point of view, Ce and Sr were well-incorporated in HA, while slight and pronounced deviations were observed for Mg and Zn, respectively. The change of the lattice parameters, crystallite size, and substituting cation occupation factors either in the Ca(I) or Ca(II) sites were further determined. Sr produced the most important HA structural changes. The in vitro biological performance was evaluated by the (i) determination of leached therapeutic cations (by inductively coupled plasma mass spectrometry) and (ii) assessment of cell behaviour by both conventional assays (e.g., proliferation-3-(4,5-dimethyl thiazol-2-yl) 5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay; cytotoxicity-lactate dehydrogenase release assay) and, for the first time, real-time cell analysis (RTCA). Three cell lines were employed: fibroblast, osteoblast, and endothelial. When monophasic, the substituted HA supported the cells' viability and proliferation without signs of toxicity. The RTCA results indicate the excellent adherence of cells. The study strived to offer a perspective on the behaviour of Ce-, Mg-, Sr-, or Zn-substituted HAs and to deliver a well-encompassing viewpoint on their effects. This can be highly important for the future development of such bioceramics, paving the road toward the identification of candidates with highly promising therapeutic effects.

Sea-Buckthorn Seed Oil Induces Proliferation of both Normal and Dysplastic Keratinocytes in Basal Conditions and under UVA Irradiation.

Past decades demonstrate an increasing interest in herbal remedies in the public eye, with as many as 80% of people worldwide using these remedies as healthcare products, including those for skin health. Sea buckthorn and its derived products (oil; alcoholic extracts), rich in flavonoids and essential fatty acids, are among these healthcare products. Specifically, sea buckthorn and its derivatives are reported to have antioxidant and antitumor activity in dysplastic skin cells. On the other hand, evidence suggests that the alteration of lipid metabolism is related to increased malignant behavior. Given the paradoxical involvement of lipids in health and disease, we investigated how sea-buckthorn seed oil, rich in long-chain fatty acids, modifies the proliferation of normal and dysplastic skin cells in basal conditions, as well as under ultraviolet A (UVA) radiation. Using real-time analysis of normal and dysplastic human keratinocytes, we showed that sea-buckthorn seed oil stimulated the proliferation of dysplastic cells, while it also impaired the ability of both normal and dysplastic cells to migrate over a denuded area. Furthermore, UVA exposure increased the expression of CD36/SR-B2, a long-chain fatty acid translocator that is related to the metastatic behavior of tumor cells.

CD36 in Alzheimer's Disease: An Overview of Molecular Mechanisms and Therapeutic Targeting.

CD36 is a membrane protein with wide distribution in the human body, is enriched in the monocyte-macrophage system and endothelial cells, and is involved in the cellular uptake of long chain fatty acids (LCFA) and oxidized low-density lipoproteins. It is also a scavenger receptor, binding hydrophobic amyloid fibrils found in the Alzheimer's disease (AD) brain. In neurobiology research, it has been mostly studied in relationship with chronic ischemia and stroke, but it was also related to amyloid clearance by microglial phagocytosis. In AD animal models, amyloid binding to CD36 has been consistently correlated with a pro-inflammatory response. Therapeutic approaches have two main focuses: CD36 blockade with monoclonal antibodies or small molecules, which is beneficial in terms of the inflammatory milieu, and upregulation of CD36 for increased amyloid clearance. The balance of the two approaches, centered on microglia, is poorly understood. Furthermore, CD36 evaluation in AD clinical studies is still at a very early stage and there is a gap in the knowledge regarding the impact of LCFA on AD progression and CD36 expression and genetic phenotype. This review summarizes the role played by CD36 in the pathogenic amyloid cascade and explore the translatability of preclinical data towards clinical research.

Caveolae as Potential Hijackable Gates in Cell Communication.

Caveolae are membrane microdomains described in many cell types involved in endocytocis, transcytosis, cell signaling, mechanotransduction, and aging. They are found at the interface with the extracellular environment and are structured by caveolin and cavin proteins. Caveolae and caveolins mediate transduction of chemical messages via signaling pathways, as well as non-chemical messages, such as stretching or shear stress. Various pathogens or signals can hijack these gates, leading to infectious, oncogenic and even caveolin-related diseases named caveolinopathies. By contrast, preclinical and clinical research have fallen behind in their attempts to hijack caveolae and caveolins for therapeutic purposes. Caveolae involvement in human disease is not yet fully explored or understood and, of all their scaffold proteins, only caveolin-1 is being considered in clinical trials as a possible biomarker of disease. This review briefly summarizes current knowledge about caveolae cell signaling and raises the hypothesis whether these microdomains could serve as hijackable "gatekeepers" or "gateways" in cell communication. Furthermore, because cell signaling is one of the most dynamic domains in translating data from basic to clinical research, we pay special attention to translation of caveolae, caveolin, and cavin research into clinical practice.

Drugs Modulating CD4+ T Cells Blood-Brain Barrier Interaction in Alzheimer's Disease.

The effect of Alzheimer's disease (AD) medications on CD4+ T cells homing has not been thoroughly investigated. CD4+ T cells could both exacerbate and reduce AD symptoms based on their infiltrating subpopulations. Proinflammatory subpopulations such as Th1 and Th17 constitute a major source of proinflammatory cytokines that reduce endothelial integrity and stimulate astrocytes, resulting in the production of amyloid ß. Anti-inflammatory subpopulations such as Th2 and Tregs reduce inflammation and regulate the function of Th1 and Th17. Recently, pathogenic Th17 has been shown to have a superior infiltrating capacity compared to other major CD4+ T cell subpopulations. Alzheimer's drugs such as donepezil (Aricept), rivastigmine (Exelon), galantamine (Razadyne), and memantine (Namenda) are known to play an important part in regulating the mechanisms of the neurotransmitters. However, little is known about the effect of these drugs on CD4+ T cell subpopulations' infiltration of the brain during AD. In this review, we focus on understanding the influence of AD drugs on CD4+ T cell subpopulation interactions with the BBB in AD. While current AD therapies improve endothelial integrity and reduce astrocytes activations, they vary according to their influence on various CD4+ T cell subpopulations. Donepezil reduces the numbers of Th1 but not Th2, Rivastigmine inhibits Th1 and Th17 but not Th2, and memantine reduces Th1 but not Treg. However, none of the current AD drugs is specifically designed to target the dysregulated balance in the Th17/Treg axis. Future drug design approaches should specifically consider inhibiting CD4+ Th17 to improve AD prognosis.

Inflammation-Related Patterns in the Clinical Staging and Severity Assessment of Chronic Kidney Disease.

Chronic kidney disease (CKD) is an irreversible loss of kidney function, and it represents a major global public health burden due to both its prevalence and its continuously increasing incidence. Mineral bone disorders (MBDs) constitute a hallmark of CKD, and alongside cardiovascular complications, they underlie a poor prognosis for these patients. Thus, our study focused on novel CKD biomarker patterns and their impact on the clinical staging of the disease. As a first testing approach, the relative expression levels of 105 proteins were assessed by the Proteome Profiler Cytokine Array Kit for pooled CKD stage 2-4 serum samples to establish an overall view regarding the proteins involved in CKD pathogenesis. Among the molecules that displayed significant dysregulation in the CKD stages, we further explored the involvement of Dickkopf-related protein 1 (Dkk-1), a recognised inhibitor of the Wnt signalling pathway, and its crosstalk with 1,25OH2D3 (calcitriol) as new players in renal bone and vascular disease. The serum levels of these two molecules were quantified by an ELISA (76 samples), and the results reveal decreasing circulating levels of Dkk-1 and calcitriol in advanced CKD stages, with their circulating expression showing a downward trend as the CKD develops. In the next step, we analysed the inflammation and MBD biomarkers' expression in CKD (by xMAP array). Our results show that the molecules involved in orchestrating the inflammatory response, interleukin-6 (IL-6) and tumour necrosis factor alpha (TNFα), as well as the mineral biomarkers osteoprotegerin (OPG), osteocalcin (OC), osteopontin (OPN), and fibroblast growth factor 23 (FGF-23), correlate with Dkk-1 and calcitriol, raising the possibility of them being potential useful CKD biomarkers. These results reveal the impact of different biomarker patterns in CKD staging and severity, thus opening up novel approaches to be explored in CKD clinical management.

Comprehensive In Vitro Testing of Calcium Phosphate-Based Bioceramics with Orthopedic and Dentistry Applications.

Recently, a large spectrum of biomaterials emerged, with emphasis on various pure, blended, or doped calcium phosphates (CaPs). Although basic cytocompatibility testing protocols are referred by International Organization for Standardization (ISO) 10993 (parts 1-22), rigorous in vitro testing using cutting-edge technologies should be carried out in order to fully understand the behavior of various biomaterials (whether in bulk or low-dimensional object form) and to better gauge their outcome when implanted. In this review, current molecular techniques are assessed for the in-depth characterization of angiogenic potential, osteogenic capability, and the modulation of oxidative stress and inflammation properties of CaPs and their cation- and/or anion-substituted derivatives. Using such techniques, mechanisms of action of these compounds can be deciphered, highlighting the signaling pathway activation, cross-talk, and modulation by microRNA expression, which in turn can safely pave the road toward a better filtering of the truly functional, application-ready innovative therapeutic bioceramic-based solutions.

CD 36: Focus on Epigenetic and Post-Transcriptional Regulation.

CD36 is a transmembrane protein involved in fatty acid translocation, scavenging for oxidized fatty acids acting as a receptor for adhesion molecules. It is expressed on macrophages, as well as other types of cells, such as endothelial and adipose cells. CD36 participates in muscle lipid uptake, adipose energy storage, and gut fat absorption. Recently, several preclinical and clinical studies demonstrated that upregulation of CD36 is a prerequisite for tumor metastasis. Cancer metastasis-related research emerged much later and has been less investigated, though it is equally or even more important. CD36 protein expression can be modified by epigenetic changes and post-transcriptional interference from non-coding RNAs. Some data indicate modulation of CD36 expression in specific cell types by epigenetic changes via DNA methylation patterns or histone tails, or through miRNA interference, but this is largely unexplored. The few papers addressing this topic refer mostly to lipid metabolism-related pathologies, whereas in cancer research, data are even more scarce. The aim of this review was to summarize major epigenetic and post-transcriptional mechanisms that impact CD36 expression in relation to various pathologies while highlighting the areas in need of further exploration.

Angiogenesis in cutaneous T-cell lymphoma - proteomic approaches.

Neoangiogenesis plays an important role in cutaneous lymphoma pathogenesis. Cutaneous T-cell lymphoma (CTCL) is characterized by the presence of malignant T-cell clones in the skin. Vascular microenvironment of lymphomas accelerates neoangiogenesis through several factors released by tumoral cells: VEGF family, bFGF and PIGF. Tumor stroma (fibroblasts, inflammatory and immune cells) also plays a crucial role, by providing additional angiogenic factors. The angiogenic process through the VEGF-VEGFR axis can promote survival, proliferation and metastasis via autocrine mechanisms in cutaneous lymphomas. Microvascular density (MVD) measures the neo-vascularization of cutaneous lymphoma, generated by the response of tumor cells, proangiogenic stromal cells, and benign T/B lymphocytes within the tumor inflammatory infiltrate. Pro-angiogenic proteins have been found to indicate the evolution and prognosis in patients with CTCL. In conclusion, anti-angiogenic therapeutic protocols can target tumor vasculature or malignant tumor cells directly or through a large number of combinations with other drugs. The integration of proteomics into clinical practice based on high-throughput technologies leads to the development of personalized medicine, adapting the specific biomarkers to the application of cancer-type specific individual drug targets.