Maintenance therapy (MT) for ovarian cancer (OC) is crucial for preventing disease relapse. Curcumol shows effective anti-OC ability and low-toxicity to the normal ovarian epithelial cells, however, its bioavailability is low. Herein, micellar loaded curcumol (MC) was prepared and the anti-tumor ability of MC were performed on OC cells. The results indicated that the IC50 values of MC in two kinds of OC cells were 37.69 ± 2.43 and 28.54 ± 1.58 μg/mL, respectively. Mechanistically, curcumol could interact with the AKTThr308 site, inhibiting the phosphorylation of FOXO3a, which promoted FOXO3a nuclear locating and recruited it to the PERK promoter, activating the ERS induced apoptosis pathway. Moreover, MC inhibited the growth of SKOV3 cells on tumor-bearing nude mice and the DiR-labeled MC could quickly accumulate in the tumor region. MC provides great feasibility to achieve efficient MT for OC based on the nanoplatforms of active ingredients from natural products.

Orthopaedic medicine often treats intervertebral disc degeneration (IVDD), which is caused by nucleus pulposus (NP) tissue damage and mechanical stress. Bioactive glasses (BGs), widely used for bone regeneration, can incorporate therapeutic ions into their network. Manganese (Mn) activates human osteoblast integrins, proliferation, and spreading. The CMnBGNPs-NPMSCs are carboxymethyl cellulose hydrogels functionalized with MnBGsNPs and NP-derived mesenchymal stem cells to treat IVDD. To ensure stability and biocompatibility of CMnBGNPs-NPMSCs were characterized for rheological properties like gelation time and swelling ratio. Gene expression analysis of PAX1, FOXF1, CA12, HBB, and OVOS2 via qRT-PCR further assessed the hydrogel's characteristics. Rat models with induced IVDD had hydrogel-MSC composite injected into their intervertebral discs for in vivo studies. Histological examination, immunohistochemical staining for inflammation and disc regeneration markers, and disc height assessments assessed therapeutic efficacy. CMnBGNPs-NPMSCs show promising results for IVDD treatment, offering a novel therapeutic strategy with clinical implications for degenerative disc diseases.

The low oral bioavailability of puerarin (Pur) affects its efficacy. Preparation of puerarin cubic liquid crystal nanoparticles (Pur-Cub) enhances the protective effect of Pur against ischemic stroke (IS) by increasing its bioavailability. The average particle size, PDI, and zeta potential of Pur-Cub were 274.70 ± 16.20 nm, 0.24 ± 0.05 and −25.30 ± 2.34 mV, respectively. Polarized light microscopy (PLM) and Small angle X-ray diffraction (SAXS) identified Pur-Cub as a cubic phase (Pn3m). The in vitro release of Pur-Cub was fast and then slow, in accordance with the biphasic kinetic equation. Pur-Cub increased the penetration of Pur in the intestine (mainly the duodenum) and significantly improved the bioavailability of Pur in the blood (304.16 %) and its distribution in the brain (1.69-fold) compared to Pur suspension. Pur-Cub narrowed down cerebral infarcts and significantly reduced levels of TNF-α, IL-1β, and IL-6 in a rat model of middle cerebral artery occlusion (MCAO).

The use of chemically modified nanocomposites for atherosclerotic plaques can open up new opportunities for studying their effect on changing the structure of the plaque itself. It was shown on the model of the greater omentum of two groups of experimental animals (rats n = 30), which were implanted with Fe@C NPs nanocomposites of 10–30 Nm size into the omentum area. Group 1 (n = 15) consisted of animals that were implanted with chemically modified Fe@C NPs nanocomposites and control group 2 (n = 15) was with non-modified Fe@C NPs nanocomposites. After 1, 2 and 3 weeks we conducted the morphological study of changes in the structure of the omentum using two dyes (Nile Blue and Sudan III), which are specific for adipose tissue. Chemically modified nanocomposites have demonstrated, in contrast to non-modified nanoparticles, to cause morphological changes in the structure of the greater omentum accompanied by the probable release of a similar antiatherogenic factor.

Atherosclerotic carotid stenosis (ACS) is a recognized risk factor for ischemic stroke. Currently, the gold diagnostic standard is Doppler ultrasound, the results of which do not provide certainty whether a given person should be qualified for surgery or not, because in some patients, carotid artery stenosis, for example at the level of 70 %, does not cause ischemic stroke in others yes. Therefore, there is a need for new methods that will clearly indicate the marker qualifying the patient for surgery. In this article we used Fourier Transform InfraRed Attenuated Total Reflectance (FTIR-ATR) spectra of serum collected from healthy and patients suffering from ACS, which had surgery were analyzed by machine learning and Principal Component Analysis (PCA) to determine chemical differences and spectroscopy marker of ACS. PCA demonstrated clearly differentiation between serum collected from healthy and non-healthy patients. Obtained results showed that in serum collected from ACS patients, higher absorbances of PO2− stretching symmetric, CH2 and CH3 symmetric and asymmetric and amide I vibrations were noticed than in control group. Moreover, lack of peak at 1106 cm−1 was observed in spectrum of serum from non-control group. As a result of spectral shifts analysis was found that the most important role in distinguishing between healthy and unhealthy patients is played by FTIR ranges caused by vibrations of PO2− phospholipids, amides III, II and CO lipid vibrations. Continuing, peaks at 1636 cm−1 and 2963 cm−1 were proposed as a potential spectroscopy markers of ACS. Finally, accuracy of obtained results higher than 90 % suggested, that FTIR-ATR can be used as an additional diagnostic tool in ACS qualifying for surgery.

Dental and orthopedic implants have become routine medical technologies for tooth replacement and bone fixation. Despite significant progress in implantology, achieving sufficient osseointegration remains a challenge, often leading to implant failure over the long term. Nanotechnology offers the potential to mimic the natural patterns of living tissues, providing a promising platform for tissue engineering and implant surface design. Among the various methods for developing nanostructures, High-Regular Laser-Induced Periodic Surface Structures (HR-LIPSS) techniques stand out for their ability to fabricate highly ordered nanostructures with excellent long-range repeatability and production efficiency. In this study, we utilized an innovative technical approach to generate traditional laser-induced superficial LIPSS nanostructures, followed by detailed surface analysis using classical microscopy and physicochemical methods. Our findings demonstrate for the first time that nanostructured LIPSS surfaces can significantly enhance cell adhesion and proliferation while providing an optimal environment for cell metabolism. Given the high reproducibility, low cost, and potential of HR-LIPSS techniques to support cell growth and differentiation, this novel technology has the potential to impact both the industrial development of new implants and clinical outcomes after implantation.

In targeted cancer therapy, antibody-drug-conjugates using mertansine (DM1)-based cytotoxic compounds rely on covalent bonds for drug conjugation. Consequently, the cytotoxic DM1 derivative released upon their proteolytic digestion is up to 1000-fold less potent than DM1 and lacks a bystander effect. To overcome these limitations, we developed a DM1 derivative (keto-DM1) suitable for bioconjugation through an acid-reversible hydrazone bond. Its acid-reversible hydrazone conjugate with biotin (B-Hz-DM1) was generated and tested for efficacy using the cetuximab-targeted Avidin-Nucleic-Acid-NanoASsembly (ANANAS) nanoparticle (NP) platform.NP-tethered B-Hz-DM1 is stable at neutral pH and releases its active moiety only in endosome/lysosome mimicking acidic pH. In vitro, the NP/Cetux/B-Hz-DM1 assembly showed high potency on MDA-MB231 breast cancer cells. In vivo both B-Hz-DM1 and NP/Cetux/B-Hz-DM1 reduced tumor growth. A significantly major effect was exerted by the nanoformulation, associated with an increased in situ tumor cell death. Keto-DM1 is a promising acid-reversible mertansine derivative for targeted delivery in cancer therapy.

The relief of joint pain is one of the main objectives in the clinical management of arthritis. Although significant strides have been made in improving management of rheumatoid and related forms of inflammatory arthritis, there are still major unmet needs for therapies that selectively provide potent, sustained and safe joint pain relief, especially among patients with osteoarthritis (OA), the most common form of arthritis. We have recently developed ProGel-Dex, an N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based thermoresponsive dexamethasone (Dex) prodrug, which forms a hydrogel upon intra-articular administration and provides sustained improvement in pain-related behavior and inflammation in rodent models of arthritis. The focus of the present study was to investigate the impact of ProGel-Dex formulation parameters on its physicochemical properties and in vivo efficacy. The results of this study provide essential knowledge for the future design of ProGel-Dex that can provide more effective, sustained and safe relief of joint pain and inflammation.