Selenium-SelK-GPX4 axis protects nucleus pulposus cells against mechanical overloading-induced ferroptosis and attenuates senescence of intervertebral disc.

Intervertebral disc degeneration (IVDD) is one of the most prevalent spinal degenerative disorders and imposes places heavy medical and economic burdens on individuals and society. Mechanical overloading applied to the intervertebral disc (IVD) has been widely recognized as an important cause of IVDD. Mechanical overloading-induced chondrocyte ferroptosis was reported, but the potential association between ferroptosis and mechanical overloading remains to be illustrated in nucleus pulposus (NP) cells. In this study, we discovered that excessive mechanical loading induced ferroptosis and endoplasmic reticulum (ER) stress, which were detected by mitochondria and associated markers, by increasing the intracellular free Ca2+ level through the Piezo1 ion channel localized on the plasma membrane and ER membrane in NP cells. Besides, we proposed that intracellular free Ca2+ level elevation and the activation of ER stress are positive feedback processes that promote each other, consistent with the results that the level of ER stress in coccygeal discs of aged Piezo1-CKO mice were significantly lower than that of aged WT mice. Then, we confirmed that selenium supplementation decreased intracellular free Ca2+ level by mitigating ER stress through upregulating Selenoprotein K (SelK) expression. Besides, ferroptosis caused by the impaired production and function of Glutathione peroxidase 4 (GPX4) due to mechanical overloading-induced calcium overload could be improved by selenium supplementation through Se-GPX4 axis and Se-SelK axis in vivo and in vitro, eventually presenting the stabilization of the extracellular matrix (ECM). Our findings reveal the important role of ferroptosis in mechanical overloading-induced IVDD, and selenium supplementation promotes significance to attenuate ferroptosis and thus alleviates IVDD, which might provide insights into potential therapeutic interventions for IVDD.

Key biomarkers in type 2 diabetes patients: A systematic review.

Type 2 diabetes mellitus (T2DM) is not just a local health issue but a significant global health burden, affecting patient outcomes and clinical management worldwide. Despite the wealth of studies reporting T2DM biomarkers, there is an urgent need for a comparative review. This review aims to provide a comprehensive analysis based on the reported T2DM biomarkers and how these are linked with other conditions, such as inflammation and wound healing. A comparative review was conducted on 24 001 study participants, including 10 024 T2DM patients and 13 977 controls (CTL; age 30-90 years). Four main profiles were extracted and analysed from the clinical reports over the past 11 years: haematological (1084 cases vs. 1458 CTL), protein (6753 cases vs. 9613 CTL), cytokine (975 cases vs. 1350 CTL) and lipid (1212 cases vs. 1556 CTL). This review provides a detailed analysis of the haematological profile in T2DM patients, highlighting fundamental changes such as increased white blood cells and platelet counts, accompanied by decreases in red blood cell counts and iron absorption. In the serum protein profile, a reduction in albumin and anti-inflammatory cytokines was noted along with an increase in globulin levels and pro-inflammatory cytokines. Furthermore, changes in lipid profiles were discussed, specifically the decreases in high-density lipoprotein (HDL) and the increases in low-density lipoprotein (LDL) and triglycerides. Understanding the changes in these four biomarker profiles is essential for developing innovative strategies to create diagnostic and prognostic tools for diabetes management.

Antibacterial Textile Coating Armoured with Aggregation-Induced Emission Photosensitisers to Prevent Healthcare-Associated Infections.

In the quest to curtail the spread of healthcare-associated infections, this work showcases the fabrication of a cutting-edge antibacterial textile coating armoured with aggregation-induced emission photosensitisers (AIE PS) to prevent bacterial colonisation on textiles. The adopted methodology includes a multi-step process using plasma polymerisation and subsequent integration of AIE PS on their surface. The antibacterial effectiveness of the coating was tested against Pseudomonas aeruginosa and Staphylococcus aureus after light irradiation for 1 h. Furthermore, antibacterial mechanistic studies revealed their ability to generate reactive oxygen species that can damage bacterial cell membrane integrity. The results of this investigation can be used to develop ground-breaking explanations for infection deterrence, principally in situations where hospital fabrics play a critical part in the transmission of diseases. The antibacterial coating for textiles developed in this study holds great promise as an efficient strategy to promote public health and reduce the danger of bacterial diseases through regular contact with fabrics.

Transforming Spirulina maxima Biomass into Ultrathin Bioactive Coatings Using an Atmospheric Plasma Jet: A New Approach to Healing of Infected Wounds.

The challenge of wound healing, particularly in patients with comorbidities such as diabetes, is intensified by wound infection and the accelerating problem of bacterial resistance to current remedies such as antibiotics and silver. One promising approach harnesses the bioactive and antibacterial compound C-phycocyanin from the microalga Spirulina maxima. However, the current processes of extracting this compound and developing coatings are unsustainable and difficult to achieve. To circumvent these obstacles, a novel, sustainable argon atmospheric plasma jet (Ar-APJ) technology that transforms S. maxima biomass into bioactive coatings is presented. This Ar-APJ can selectively disrupt the cell walls of S. maxima, converting them into bioactive ultrathin coatings, which are found to be durable under aqueous conditions. The findings demonstrate that Ar-APJ-transformed bioactive coatings show better antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. Moreover, these coatings exhibit compatibility with macrophages, induce an anti-inflammatory response by reducing interleukin 6 production, and promote cell migration in keratinocytes. This study offers an innovative, single-step, sustainable technology for transforming microalgae into bioactive coatings. The approach reported here has immense potential for the generation of bioactive coatings for combating wound infections and may offer a significant advance in wound care research and application.

Spontaneous formation of MXene-oxidized sono/chemo-dynamic sonosensitizer/nanocatalyst for antibacteria and bone-tissue regeneration.

Prolonged and incurable bacterial infections in soft tissue and bone are currently causing large challenges in the clinic. Two-dimensional (2D) materials have been designed to address these issues, but materials with satisfying therapeutic effects are still needed. Herein, CaO2-loaded 2D titanium carbide nanosheets (CaO2-TiOx@Ti3C2, C-T@Ti3C2) were developed. Surprisingly, this nanosheet exhibited sonodynamic ability, in which CaO2 caused the in situ oxidation of Ti3C2 MXene to produce acoustic sensitiser TiO2 on its surface. In addition, this nanosheet displayed chemodynamic features, which promoted a Fenton reaction triggered by self-supplied H2O2. We detected that C-T@Ti3C2 nanosheets increased reactive oxygen species (ROS) production in response to sonodynamic therapy, which displayed an ideal antibacterial effect. Furthermore, these nanoreactors facilitated the deposition of Ca2+, which promoted osteogenic transformation and enhanced bone quality in osteomyelitis models. Herein, a wound healing model and prosthetic joint infection (PJI) model were established, and the C-T@Ti3C2 nanosheets played a protective role in these models. Taken together, the results indicated that the C-T@Ti3C2 nanosheets function as a multifunctional instrument with sonodynamic features, which might reveal information regarding the treatment of bacterial infections during wound healing.

Surfaces Containing Sharp Nanostructures Enhance Antibiotic Efficacy.

The ever-increasing rate of medical device implantations is met by a proportionately high burden of implant-associated infections. To mitigate this threat, much research has been directed toward the development of antibacterial surface modifications by various means. One recent approach involves surfaces containing sharp nanostructures capable of killing bacteria upon contact. Herein, we report that the mechanical interaction between Staphylococcus aureus and such surface nanostructures leads to a sensitization of the pathogen to the glycopeptide antibiotic vancomycin. We demonstrate that this is due to cell wall damage and impeded bacterial defenses against reactive oxygen species. The results of this study promise to be impactful in the clinic, as a combination of nanostructured antibacterial surfaces and antibiotics commonly used in hospitals may improve antimicrobial therapy strategies, helping clinicians to prevent and treat implant-associated infections using reduced antibiotic concentrations instead of relying on invasive revision surgeries with often poor outcomes.

A Novel Nanostructured Surface on Titanium Implants Increases Osseointegration in a Sheep Model.

BACKGROUND: A nanostructured titanium surface that promotes antimicrobial activity and osseointegration would provide the opportunity to create medical implants that can prevent orthopaedic infection and improve bone integration. Although nanostructured surfaces can exhibit antimicrobial activity, it is not known whether these surfaces are safe and conducive to osseointegration. QUESTIONS/PURPOSES: Using a sheep animal model, we sought to determine whether the bony integration of medical-grade, titanium, porous-coated implants with a unique nanostructured surface modification (alkaline heat treatment [AHT]) previously shown to kill bacteria was better than that for a clinically accepted control surface of porous-coated titanium covered with hydroxyapatite (PCHA) after 12 weeks in vivo. The null hypothesis was that there would be no difference between implants with respect to the primary outcomes: interfacial shear strength and percent intersection surface (the percentage of implant surface with bone contact, as defined by a micro-CT protocol), and the secondary outcomes: stiffness, peak load, energy to failure, and micro-CT (bone volume/total volume [BV/TV], trabecular thickness [Tb.Th], and trabecular number [Tb.N]) and histomorphometric (bone-implant contact [BIC]) parameters. METHODS: Implants of each material (alkaline heat-treated and hydroxyapatite-coated titanium) were surgically inserted into femoral and tibial metaphyseal cancellous bone (16 per implant type; interference fit) and in tibial cortices at three diaphyseal locations (24 per implant type; line-to-line fit) in eight skeletally mature sheep. At 12 weeks postoperatively, bones were excised to assess osseointegration of AHT and PCHA implants via biomechanical push-through tests, micro-CT, and histomorphometry. Bone composition and remodeling patterns in adult sheep are similar to that of humans, and this model enables comparison of implants with ex vivo outcomes that are not permissible with humans. Comparisons of primary and secondary outcomes were undertaken with linear mixed-effects models that were developed for the cortical and cancellous groups separately and that included a random effect of animals, covariates to adjust for preoperative bodyweight, and implant location (left/right limb, femoral/tibial cancellous, cortical diaphyseal region, and medial/lateral cortex) as appropriate. Significance was set at an alpha of 0.05. RESULTS: The estimated marginal mean interfacial shear strength for cancellous bone, adjusted for covariates, was 1.6 MPa greater for AHT implants (9.3 MPa) than for PCHA implants (7.7 MPa) (95% CI 0.5 to 2.8; p = 0.006). Similarly, the estimated marginal mean interfacial shear strength for cortical bone, adjusted for covariates, was 6.6 MPa greater for AHT implants (25.5 MPa) than for PCHA implants (18.9 MPa) (95% CI 5.0 to 8.1; p < 0.001). No difference in the implant-bone percent intersection surface was detected for cancellous sites (cancellous AHT 55.1% and PCHA 58.7%; adjusted difference of estimated marginal mean -3.6% [95% CI -8.1% to 0.9%]; p = 0.11). In cortical bone, the estimated marginal mean percent intersection surface at the medial site, adjusted for covariates, was 11.8% higher for AHT implants (58.1%) than for PCHA (46.2% [95% CI 7.1% to 16.6%]; p < 0.001) and was not different at the lateral site (AHT 75.8% and PCHA 74.9%; adjusted difference of estimated marginal mean 0.9% [95% CI -3.8% to 5.7%]; p = 0.70). CONCLUSION: These data suggest there is stronger integration of bone on the AHT surface than on the PCHA surface at 12 weeks postimplantation in this sheep model. CLINICAL RELEVANCE: Given that the AHT implants formed a more robust interface with cortical and cancellous bone than the PCHA implants, a clinical noninferiority study using hip stems with identical geometries can now be performed to compare the same surfaces used in this study. The results of this preclinical study provide an ethical baseline to proceed with such a clinical study given the potential of the alkaline heat-treated surface to reduce periprosthetic joint infection and enhance implant osseointegration.

Effects of Supplemental Drugs on Hexaminolevulinate (HAL)-Induced PpIX Fluorescence in Bladder Cancer Cell Suspensions.

Seven different inhibitors of the heme metabolic pathway were applied in combination with HAL to study the formation of PpIX in bladder cancer HT1197 and normal fibroblast HFFF2 cells ex vivo, specifically with the aim to increase the fluorescence contrast between cancer and non-cancer cells. The mRNA expression of enzymes involved in the heme biosynthesis pathway were measured via PCR following incubation with the drugs in order to link the fluorescence levels and metabolic activity. The exogenous administration of HAL does lead to cancer-specific PpIX accumulation. However, the contrast between cancer and normal cells in suspension was not enhanced by the enzyme inhibitors and iron-chelating agents tested, nor did the mRNA expression necessarily correlate with the fluorescence intensity. The results indicate that a difference in the metabolic activity of cells in suspension may limit the applicability of exogenous enzyme inhibitor administration as a mean to improve the fluorescence-based detection of cancer cells shed in body fluids.

Fluid Flow Dependency in Immunoselective Cell Capture via Liquid Biopsy.

Liquid biopsy targets rare cells that overexpress disease-specific membrane markers and capture these cells via immunoaffinity. The diagnosis efficiency of liquid biopsy can be impaired by the presence of healthy adherent cells also expressing the same biomarkers. Here, we investigated the effect of settling times and rinsing flow rates on the efficiency of EpCAM-based immunocapture using both simulation and experiments with three different cell types. Cell-surface adhesion forces and shear rates were calculated to define the range of rinsing flow rates to test experimentally. Healthy adherent cells did not adhere to blocked immunofunctionalized surfaces within the timeframe of the experiment; however, healthy EpCAM positive cells did bind to the surface to some extent. The greatest difference in capture efficiency was obtained using a high rinsing flow rate of 25 mL/min following 40 min static incubation, indicating that optimizing rinsing flow rates could be a viable option to capture, more specifically, cancer cells overexpressing EpCAM.

Disruption of Enterococcus Faecalis biofilms using individual and plasma polymer encapsulated D-amino acids.

OBJECTIVE: Our aim was to assess the anti-biofilm ability of previously unverified individual D-amino acids (DAAs), to produce plasma polymer encapsulated DAAs (PPEDAAs), to measure the shell thickness and subsequent release of DAAs, and to assess the effects of PPEDAAs on Enterococcus faecalis biofilms. MATERIALS AND METHODS: Microtitre tray assays were used to evaluate the effect of individual DAAs (D-leucine, D-methionine, D-tryptophan, and D-tyrosine) on E. faecalis biofilms of different maturity. A mixture and individual DAAs were encapsulated with a plasma polymer for 10, 20, 40, and 60 min. The shell thickness of PPEDAAs was analyzed by ultra-high-resolution scanning electron microscopy. The release of DAAs from the PPEDAAs encapsulated for 60 min was measured over 7 days using high-performance liquid chromatography. Static biofilms were used to assess the effect of PPEDAAs on E. faecalis biofilms. RESULTS: Individual DAAs reduced biofilm formation to various degrees, according to the DAA and the experimental times. The shell thicknesses of the PPEDAAs ranged between 31 and 76 nm and increased with encapsulation time. Diffusion of DAAs from the PPEDAAs occurred over 60 min for encapsulated D-leucine, D-methionine, and D-tyrosine and up to 7 days for D-tryptophan. PPEDAAs disrupted biofilms at every experimental time. CONCLUSIONS: PPEDAAs of various shell thickness can be produced with the proposed methodology, DAAs are subsequently released, and the anti-biofilm activity remains unaltered. CLINICAL RELEVANCE: Individual DAAs and PPEDAAs have anti-biofilm ability and can be considered as part of a biological strategy in endodontics.

Diagnosis of Prostate Cancer and Prostatitis Using near Infra-Red Fluorescent AgInSe/ZnS Quantum Dots.

The link between the microbiome and cancer has led researchers to search for a potential probe for intracellular targeting of bacteria and cancer. Herein, we developed near infrared-emitting ternary AgInSe/ZnS quantum dots (QDs) for dual bacterial and cancer imaging. Briefly, water-soluble AgInSe/ZnS QDs were synthesized in a commercial kitchen pressure cooker. The as-synthesized QDs exhibited a spherical shape with a particle diameter of 4.5 ± 0.5 nm, and they were brightly fluorescent with a photoluminescence maximum at 705 nm. The QDs showed low toxicity against mouse mammary carcinoma (FM3A-Luc), mouse colon carcinoma (C26), malignant fibrous histiocytoma-like (KM-Luc/GFP) and prostate cancer cells, a greater number of accumulations in Staphylococcus aureus, and good cellular uptake in prostate cancer cells. This work is an excellent step towards using ternary QDs for diagnostic and guided therapy for prostate cancer.

Comparative Study of Natural Terpenoid Precursors in Reactive Plasmas for Thin Film Deposition.

If plasma polymer thin films are to be synthesised from sustainable and natural precursors of chemically heterogeneous composition, it is important to understand the extent to which this composition influences the mechanism of polymerisation. To this end, a well-studied monoterpene alcohol, terpinen-4-ol, has been targeted for a comparative study with the naturally occurring mix of terpenes (viz. Melaleuca alternifolia oil) from which it is commonly distilled. Positive ion mode mass spectra of both terpinen-4-ol and M. alternifolia oil showed a decrease in disparities between the type and abundance of cationic species formed in their respective plasma environments as applied plasma power was increased. Supplementary biological assay revealed the antibacterial action of both terpinen-4-ol and M. alternifolia derived coatings with respect to S. aureus bacteria, whilst cytocompatibility was demonstrated by comparable eukaryotic cell adhesion to both coatings. Elucidating the processes occurring within the reactive plasmas can enhance the economics of plasma polymer deposition by permitting use of the minimum power, time and precursor pre-processing required to control the extent of monomer fragmentation and fabricate a film of the desired thickness and functionality.

The Influence of Nanoparticle Shape on Protein Corona Formation.

Nanoparticles have become an important utility in many areas of medical treatment such as targeted drug and treatment delivery as well as imaging and diagnostics. These advances require a complete understanding of nanoparticles' fate once placed in the body. Upon exposure to blood, proteins adsorb onto the nanoparticles surface and form a protein corona, which determines the particles' biological fate. This study reports on the protein corona formation from blood serum and plasma on spherical and rod-shaped nanoparticles. These two types of mesoporous silica nanoparticles have identical chemistry, porosity, surface potential, and size in the y-dimension, one being a sphere and the other a rod shape. The results show a significantly larger amount of protein attaching from both plasma and serum on the rod-like particles compared to the spheres. Interrogation of the protein corona by liquid chromatography-mass spectrometry reveals shape-dependent differences in the adsorption of immunoglobulins and albumin proteins from both plasma and serum. This study points to the need for taking nanoparticle shape into consideration because it can have a significant impact on the fate and therapeutic potential of nanoparticles when placed in the body.

Biocompatible functionalisation of nanoclays for improved environmental remediation.

Among the wide range of materials used for remediating environmental contaminants, modified and functionalised nanoclays show particular promise as advanced sorbents, improved dispersants, or biodegradation enhancers. However, many chemically modified nanoclay materials are incompatible with living organisms when they are used in natural systems with detrimental implications for ecosystem recovery. Here we critically review the pros and cons of functionalised nanoclays and provide new perspectives on the synthesis of environmentally friendly varieties. Particular focus is given to finding alternatives to conventional surfactants used in modified nanoclay products, and to exploring strategies in synthesising nanoclay-supported metal and metal oxide nanoparticles. A large number of promising nanoclay-based sorbents are yet to satisfy environmental biocompatibility in situ but opportunities are there to tailor them to produce "biocompatible" or regenerative/reusable materials.

Field Deployable Method for Gold Detection Using Gold Pre-Concentration on Functionalized Surfaces.

Keywords: surface chemistry, plasma polymerization, salinization, gold sensing.

Probing Hexaminolevulinate Mediated PpIX Fluorescence in Cancer Cell Suspensions in the Presence of Chemical Adjuvants.

Exogenous administration of hexaminolevulinate (HAL) induces fluorescent protoporphyrin IX (PpIX) accumulation preferentially in cancer cells. However, the PpIX fluorescence intensities between noncancer and cancer cells are highly variable. The contrast between cancer and noncancer cells may be insufficient to reliably discriminate, especially at the single cell level in cancer diagnostics. This study examines the use of the chemical adjuvants dimethylsulphoxide (DMSO) or deferoxamine (DFO) to enhance the HAL induced PpIX accumulation in cancer cells. Our results showed that in some of the incubation conditions tested, the addition of DFO with HAL significantly increased PpIX 21 fluorescence of adherent monolayer cancer cells, but this was never the case for cells in suspension. Permeabilisation with DMSO did not increase PpIX fluorescence. Cell-to-cell interaction may well play an important role in the PpIX accumulation when suspended cells are treated in HAL and adjuvant chemicals.

Ghrelin protects against osteoarthritis through interplay with Akt and NF-κB signaling pathways.

Osteoarthritis (OA) is a common chronic degenerative disease characterized by degeneration in the joints and subsequent destruction of cartilage and bone, yet much remains to be elucidated regarding its molecular mechanism. Ghrelin is a recently discovered neuropeptide with anti-inflammatory actions, but it is unknown whether ghrelin is involved in OA. Human primary chondrocyte and cartilage samples were collected from patients with OA, and the expression pattern of ghrelin was assessed. Human chondrocyte and cartilage samples were stimulated with IL-1ß and TNF-α, and exogenous ghrelin-alleviated disorganization of catabolism and anabolism were mediated by IL-1ß and TNF-α. Destabilization of the medial meniscus and anterior cruciate ligament transection models were established in wild-type mice that were administered ghrelin or PBS. Severity of inflammation and degeneration in the joints were determined by measuring the levels of various inflammatory cytokines and degeneration-associated molecules. Ghrelin down-regulated the production of various inflammatory cytokines, inhibited apoptosis of chondrocytes, decreased the levels of metalloproteinases (including matrix metalloproteinase-13 and a disintegrin and metalloproteinase with thrombospondin motif-5), and maintained the expression of critical matrix components, such as aggrecan and collagen 2. Moreover, suppression of the Akt signaling pathway and activation of NF-κB signaling in chondrocytes during OA development was antagonized by ghrelin administration. This supports the assessment of ghrelin as a potential therapeutic approach to treat degenerative cartilage diseases, including OA.-Qu, R., Chen, X., Wang, W., Qiu, C., Ban, M., Guo, L., Vasilev, K., Chen, J., Li, W., Zhao, Y. Ghrelin protects against osteoarthritis through interplay with Akt and NF-κB signaling pathways.

Mechanistic relationship between biodegradation and bioaccumulation. Practical outcomes.

According to the REACH Regulation, for all substances manufactured or imported in amounts of 10 or more tons per year, that are not exempted from the registration requirement, a Chemical Safety Assessment (CSA) must be conducted. According to CSA criteria, for these substances persistent, bioaccumulative and toxic (PBT), and very persistent and very bioaccumulative (vPvB) assessment is requested. In order to reduce the number of applications of the expensive bioaccumulation test it seems useful to search thresholds for other related parameters above which no bioaccumulation is observed. Given the known relationship between ready biodegradability and bioaccumulation, one such parameter is biodegradation. This article addresses this relationship in searching for BOD threshold above which no vB and B chemicals could be observed. It was found that the regulatory criteria for persistency could be used for identification of not vB and B chemicals. In addition, fish liver metabolism is determined as the most significant factor in reducing of maximum bioaccumulation potential of the chemicals. It was found that parameters associated with the models simulating fish metabolism could be also used for identification of not vB and B chemicals.

Surface Functionalization of Exposed Core Glass Optical Fiber for Metal Ion Sensing.

One of the biggest challenges associated with exposed core glass optical fiber-based sensing is the availability of techniques that can be used to generate reproducible, homogeneous and stable surface coating. We report a one step, solvent free method for surface functionalization of exposed core glass optical fiber that allows achieving binding of fluorophore of choice for metal ion sensing. The plasma polymerization-based method yielded a homogeneous, reproducible and stable coating, enabling high sensitivity aluminium ion sensing. The sensing platform reported in this manuscript is versatile and can be used to bind different sensing molecules opening new avenues for optical fiber-based sensing.

Development of a Decision Tree for Mitochondrial Dysfunction: Uncoupling of Oxidative Phosphorylation.

Mitochondrial dysfunction is the result of a number of processes including the uncoupling of oxidative phosphorylation. This study outlines the development of a decision tree-based profiling scheme capable of assigning chemicals to one of six confidence-based categories. The decision tree is based on a set of structural alerts and physicochemical boundaries identified from a detailed study of the literature. The physicochemical boundaries define a chemical relationship with both log P and p Ka. The study also outlines how the decision tree can be used to profile databases through an analysis of the publically available databases in the OECD QSAR Toolbox. This analysis enabled a set of additional structural alerts to be identified that are of concern for protonophoric ability. The decision tree will be incorporated in the OECD QSAR Toolbox V4.3. The intended usage is to group the chemicals into categories of chronic human health and environmental toxicological end points.