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Osteoarthritis (OA) is a degenerative musculoskeletal disorder affecting the whole synovial joint and globally impacts more than one in five individuals aged 40 and over, representing a huge socioeconomic burden. Drug penetration into and retention within the joints are major challenges in the development of regenerative therapies for OA. During the recent years, polymeric nanoparticles (PNPs) have emerged as promising drug carrier candidates due to their biodegradable properties, nanoscale structure, functional versatility, and reproducible manufacturing, which makes them particularly attractive for cartilage penetration and joint retention. In this review, we discuss the current development state of natural and synthetic PNPs for drug delivery and OA treatment. Evidence from in vitro and pre-clinical in vivo studies is used to show how disease pathology and key cellular pathways of joint inflammation are modulated by these nanoparticle-based therapies. Furthermore, we compare the biodegradability and surface modification of these nanocarriers in relation to the drug release profile and tissue targeting. Finally, the main challenges for nanoparticle delivery to the cartilage are discussed, as a function of disease state and physicochemical properties of PNPs such as size and surface charge.

This paper addresses part of a wider project aiming at the development of a microchannel based heat sink to cool photovoltaic panels. The work presented here gives emphasis to working conditions leading to flow boiling in a microchannel and focuses on flow instabilities and on the potential effect of surface microstructuring in heat transfer enhancement and in controlling such instabilities. After identifying the flow boiling regimes, the observed phenomena are qualitatively and quantitatively described. The results show that a regular pattern of microcavities on the surface to cool enhances heat transfer and promotes the occurrence of a more stable flow.

Chronic lower back pain caused by intervertebral disc degeneration and osteoarthritis (OA) are highly prevalent chronic diseases. Although pain management and surgery can alleviate symptoms, no disease-modifying treatments are available. mRNA delivery could halt inflammation and degeneration and induce regeneration by overexpressing anti-inflammatory cytokines or growth factors involved in cartilage regeneration. Here, we investigated poly(amidoamine)-based polymeric nanoparticles to deliver mRNA to human joint and intervertebral disc cells. Human OA chondrocytes, human nucleus pulposus (NP) cells, human annulus fibrosus (AF) cells, fibroblast-like synoviocytes (FLS) and M1-like macrophages were cultured and transfected with uncoated or PGA-PEG-coated nanoparticles loaded with EGFP-encoding mRNA. Cell viability and transfection efficiency were analyzed for all cell types. Nanoparticle internalization was investigated in FLS and M1-like macrophages. No significant decrease in cell viability was observed in most conditions. Only macrophages showed a dose-dependent reduction of viability. Transfection with either nanoparticle version resulted in EGFP expression in NP cells, AF cells, OA chondrocytes and FLS. Macrophages showed internalization of nanoparticles by particle–cell co-localization, but no detectable expression of EGFP. Taken together, our data show that poly (amidoamine)-based nanoparticles can be used for mRNA delivery into cells of the human joint and intervertebral disc, indicating its potential future use as an mRNA delivery system in OA and IVDD, except for macrophages.

Disulfide-containing poly(amidoamine) (PAA) is a cationic and bioreducible polymer, with potential use as a nanocarrier for mRNA delivery in the treatment of several diseases including osteoarthritis (OA). Successful transfection of joint cells with PAA-based nanoparticles (NPs) was shown previously, but cell uptake, endosomal escape and nanoparticle biodegradation were not studied in detail. In this study, C28/I2 human chondrocytes were transfected with NPs co-formulated with a PEG-polymer coating and loaded with EGFP mRNA for confocal imaging of intracellular trafficking and evaluation of transfection efficiency. Compared with uncoated NPs, PEG-coated NPs showed smaller particle size, neutral surface charge, higher colloidal stability and superior transfection efficiency. Furthermore, endosomal entrapment of these PEG-coated NPs decreased over time and mRNA release could be visualized both in vitro and in live cells. Importantly, cell treatment with modulators of the intracellular reducing environment showed that glutathione (GSH) concentrations affect translation of the mRNA payload. Finally, we applied a D-optimal experimental design to test different polymer-to-RNA loading ratios and dosages, thus obtaining an optimal formulation with up to ≈80% of GFP-positive cells and without toxic effects. Together, the biocompatibility and high transfection efficiency of this system may be a promising tool for intra-articular delivery of therapeutical mRNA in OA treatment.

Sea turtles migrate thousands of miles annually between foraging and breeding areas, carrying dozens of epibiont species with them on their journeys. Most sea turtle epibiont studies have focused on large-sized organisms, those visible to the naked eye. Here, we report previously undocumented levels of epibiont abundance and biodiversity for loggerhead sea turtles (Caretta caretta), by focusing on the microscopic meiofauna. During the peak of the 2018 loggerhead nesting season at St. George Island, Florida, USA, we sampled all epibionts from 24 carapaces. From the subsamples, we identified 38,874 meiofauna individuals belonging to 20 higher taxa. This means 810,753 individuals were recovered in our survey, with an average of 33,781 individuals per carapace. Of 6992 identified nematodes, 111 different genera were observed. To our knowledge, such levels of sea turtle epibiont abundance and diversity have never been recorded. Loggerhead carapaces are without doubt hotspots of meiofaunal and nematode diversity, especially compared to other non-sedimentary substrates. The posterior carapace sections harbored higher diversity and evenness compared to the anterior and middle sections, suggesting increased colonization and potentially facilitation favoring posterior carapace epibiosis, or increased disturbance on the anterior and middle carapace sections. Our findings also shed new light on the meiofauna paradox: “How do small, benthic meiofauna organisms become cosmopolitan over large geographic ranges?” Considering high loggerhead epibiont colonization, the large distances loggerheads migrate for reproduction and feeding, and the evolutionary age and sheer numbers of sea turtles worldwide, potentially large-scale exchange and dispersal for meiofauna through phoresis is implied. We distinguished different groups of loggerhead carapaces based on divergent epibiont communities, suggesting distinct epibiont colonization processes. These epibiont observations hold potential for investigating loggerhead movements and, hence, their conservation.

Sugar-induced metabolic imbalances are a major health problem since an excessive consumption of saccharides has been linked to greater obesity rates at a global level. Sucrose, a disaccharide composed of 50% glucose and 50% fructose, is commonly used in the food industry and found in a range of fast, restaurant, and processed foods. Herein, we investigated the effects of a TRPC4/TRPC5 blocker, ML204, in the metabolic imbalances triggered by early exposure to sucrose-enriched diet in mice. TRPC4 and TRPC5 belong to the family of non-selective Ca+2 channels known as transient receptor potential channels. High-sucrose (HS)-fed animals with hyperglycaemia and dyslipidaemia, were accompanied by increased body mass index. mesenteric adipose tissue accumulation with larger diameter cells and hepatic steatosis in comparison to those fed normal diet. HS mice also exhibited enhanced adipose, liver, and pancreas TNFα and VEGF levels. ML204 exacerbated hyperglycaemia, dyslipidaemia, fat tissue deposition, hepatic steatosis, and adipose tissue and liver TNFα in HS-fed mice. Normal mice treated with the blocker had greater hepatic steatosis and adipose tissue cell numbers/diameter than those receiving vehicle, but showed no significant changes in tissue inflammation, glucose, and lipid levels. The results indicate that TRPC4/TRPC5 protect against the metabolic imbalances caused by HS ingestion.

The theoretical analysis for the design of microreactors in biodiesel production is a complicated task due to the complex liquid-liquid flow and mass transfer processes, and the transesterification reaction that takes place within these microsystems. Thus, computational simulation is an important tool that aids in understanding the physical-chemical phenomenon and, consequently, in determining the suitable conditions that maximize the conversion of triglycerides during the biodiesel synthesis. A diffusive-convective-reactive coupled nonlinear mathematical model, that governs the mass transfer process during the transesterification reaction in parallel plates microreactors, under isothermal conditions, is here described. A hybrid numerical-analytical solution via the Generalized Integral Transform Technique (GITT) for this partial differential system is developed and the eigenfunction expansions convergence rates are extensively analyzed and illustrated. The heuristic method of Particle Swarm Optimization (PSO) is applied in the inverse analysis of the proposed direct problem, to estimate the reaction kinetics constants, which is a critical step in the design of such microsystems. The results present a good agreement with the limited experimental data in the literature, but indicate that the GITT methodology combined with the PSO approach provide a reliable computational algorithm for direct-inverse analysis in such reactive mass transfer problems.

This study addresses the combination of customized surface modification with the use of nanofluids, to infer on its potential to enhance pool boiling heat transfer. Hydrophilic surfaces patterned with superhydrophobic regions are prepared and used to act as surface interfaces with nanofluids (water with gold, silver and alumina nanoparticles) and infer on the effect of the nature and concentration of the nanoparticles in bubble dynamics and consequently in heat transfer processes. The main qualitative and quantitative analysis was based on extensive post-processing of synchronized high-speed and thermographic images. The results show an evident benefice of using biphilic patterns, but with well-stablished distances between the superhydrophobic regions. Such patterns allow a controlled bubble coalescence, which promotes fluid convection at the hydrophilic surface between the superhydrophobic regions, which clearly contributes to cool down the surface. The effect of the nanofluids, for the low concentrations used here, was observed to play a minor role.

Metabolic syndrome (MS) is a complex pathology characterized by visceral adiposity, insulin resistance, arterial hypertension, and dyslipidaemia. It has become a global epidemic associated with increased consumption of high-calorie, low-fibre food and sedentary habits. Some of its underlying mechanisms have been identified, with hypoadiponectinemia, inflammation and oxidative stress as important factors for MS establishment and progression. Alterations in adipokine levels may favour glucotoxicity and lipotoxicity which, in turn, contribute to inflammation and cellular stress responses within the adipose, pancreatic and liver tissues, in addition to hepatic steatosis. The multiple mechanisms of MS make its clinical management difficult, involving both non-pharmacological and pharmacological interventions. Transient receptor potential (TRP) channels are non-selective calcium channels involved in a plethora of physiological events, including energy balance, inflammation and oxidative stress. Evidence from animal models of disease has contributed to identify their specific contributions to MS and may help to tailor clinical trials for the disease. In this context, the oxidative stress sensors TRPV1, TRPA1 and TRPC5, play major roles in regulating inflammatory responses, thermogenesis and energy expenditure. Here, the interplay between these TRP channels and oxidative stress in MS is discussed in the light of novel therapies to treat this syndrome.

Rheumatoid arthritis (RA) is a painful inflammatory disease of the joints which affects a considerable proportion of the world population, mostly women. If not adequately treated, RA patients can become permanently disabled. Importantly, not all the patients respond to the available anti-rheumatic therapies, which also present diverse side effects. In this context, monitoring of treatment response is pivotal to avoid unnecessary side effects and costs towards an ineffective therapy. Herein, we performed a pilot study to investigate the potential use of flow cytometry and attenuated total reflection–Fourier transform infrared (ATR-FTIR) spectroscopy as measures to identify responders and non-responders to leflunomide, a disease-modifying drug used in the treatment of RA patients. The evaluation of peripheral blood CD62L+ polymorphonuclear cell numbers and ATR-FTIR vibrational modes in plasma were able to discriminate responders to leflunomide (LFN) three-months after therapy has started. Overall, the results indicate that both flow cytometry and ATR-FTIR can potentially be employed as additional measures to monitor early treatment response to LFN in RA patients.