New Perspectives and Prospects of microRNA Delivery in Diabetic Wound Healing.

The remarkable potential of microRNAs (miRNAs) as a class of biotherapeutic agents in the treatment of diverse pathological conditions has garnered significant interest in recent years. To heal both acute and chronic wounds, miRNAs work by post-transcriptionally controlling various proteins and the pathways that are linked to them. Diabetes mellitus predisposes to several macro- and microvascular defects of end organs such as atherosclerosis, peripheral artery disease, retinopathy, nephropathy, neuropathy, and impaired wound healing. Here, miRNAs emerge as a beacon of hope, with the capacity to heal diabetic wounds by precisely modulating the expression of genes involved in the healing process. Despite the therapeutic promise, the journey to realizing the full potential of miRNAs is fraught with challenges. Their intrinsic instability and the inefficient delivery into target cells pose significant barriers to their clinical application. Consequently, a major focus of current research is the discovery of novel miRNAs and the development of innovative delivery systems that can effectively transport these nucleic acids into the cells where they are needed most. This review delves into the intricate roles that miRNAs play at various stages of diabetic wound healing, providing a comprehensive overview of the latest research findings. The review also addresses the obstacles and opportunities that come with translating miRNA-based strategies into clinical practice, offering a critical assessment of the field's advancements and the hurdles that remain to be overcome. SIGNIFICANCE STATEMENT: The potential of microRNA delivery using new biological or nonbiological carriers may create a revolutionary treatment method for chronic wounds of diabetes.

Preparation, stability, and antibacterial activity of carboxymethylated Anemarrhena asphodeloides polysaccharide-chitosan nanoparticles loaded curcumin.

In present study, polysaccharide polyelectrolyte nanoparticles (CMAAP-CS NPs) were constructed by mixing carboxymethylated Anemarrhena asphodeloides polysaccharide (CMAAP) and chitosan (CS). CMAAP-CS NPs were applied as carrier to improve the bioavailability and stability of curcumin (Cur). The average particle size of CMAAP-CS NPs was 216.60 ± 4.21 nm and the entrapment efficiency of Cur reached 82.50 ± 2.09 %. The simulated digestion experiments in vitro confirmed that the bioavailability of Cur loaded in CMAAP-CS NPs was 59.84 ± 0.03 % after saliva, gastric and intestinal digestion, which was obvious higher than 21.57 ± 0.07 % of free Cur under the same conditions. The results of stability testing revealed that CMAAP-CS NPs could markedly reduce the degradation of Cur against storage, heating, UV light treatment, and neutral pH. This study provided promising polyelectrolyte complex loaded hydrophobic nutrients in medicine industry.

[Role and mechanism of macrophage-mediated osteoimmune in osteonecrosis of the femoral head].

Objective: To summarize the research progress on the role of macrophage-mediated osteoimmune in osteonecrosis of the femoral head (ONFH) and its mechanisms. Methods: Recent studies on the role and mechanism of macrophage-mediated osteoimmune in ONFH at home and abroad were extensively reviewed. The classification and function of macrophages were summarized, the osteoimmune regulation of macrophages on chronic inflammation in ONFH was summarized, and the pathophysiological mechanism of osteonecrosis was expounded from the perspective of osteoimmune, which provided new ideas for the treatment of ONFH. Results: Macrophages are important immune cells involved in inflammatory response, which can differentiate into classically activated type (M1) and alternatively activated type (M2), and play specific functions to participate in and regulate the physiological and pathological processes of the body. Studies have shown that bone immune imbalance mediated by macrophages can cause local chronic inflammation and lead to the occurrence and development of ONFH. Therefore, regulating macrophage polarization is a potential ONFH treatment strategy. In chronic inflammatory microenvironment, inhibiting macrophage polarization to M1 can promote local inflammatory dissipation and effectively delay the progression of ONFH; regulating macrophage polarization to M2 can build a local osteoimmune microenvironment conducive to bone repair, which is helpful to necrotic tissue regeneration and repair to a certain extent. Conclusion: At present, it has been confirmed that macrophage-mediated chronic inflammatory immune microenvironment is an important mechanism for the occurrence and development of ONFH. It is necessary to study the subtypes of immune cells in ONFH, the interaction between immune cells and macrophages, and the interaction between various immune cells and macrophages, which is beneficial to the development of potential therapeutic methods for ONFH.

Novel insights of EZH2-mediated epigenetic modifications in degenerative musculoskeletal diseases.

Degenerative musculoskeletal diseases (Osteoporosis, Osteoarthritis, Degenerative Spinal Disease and Sarcopenia) are pathological conditions that affect the function and pain of tissues such as bone, cartilage, and muscles, and are closely associated with ageing and long-term degeneration. Enhancer of zeste homolog 2 (EZH2), an important epigenetic regulator, regulates gene expression mainly through the PRC2-dependent trimethylation of histone H3 at lysine 27 (H3K27me3). Increasing evidence suggests that EZH2 is involved in several biological processes closely related to degenerative musculoskeletal diseases, such as osteogenic-adipogenic differentiation of bone marrow mesenchymal stem cells, osteoclast activation, chondrocyte functional status, and satellite cell proliferation and differentiation, mainly through epigenetic regulation (H3K27me3). Therefore, the synthesis and elucidation of the role of EZH2 in degenerative musculoskeletal diseases have attracted increasing attention. In addition, although EZH2 inhibitors have been approved for clinical use, whether they can be repurposed for the treatment of degenerative musculoskeletal diseases needs to be considered. Here, we reviewed the role of EZH2 in the development of degenerative musculoskeletal diseases and brought forward prospects of its pharmacological inhibitors in the improvement of the treatment of the diseases.

Establishment of a reverse transcription recombinase-aided amplification detection method for porcine group a rotavirus.

Porcine rotavirus type A (PoRVA) is the main cause of dehydration and diarrhea in piglets, which has a great impact on the development of the pig industry worldwide. A rapid, accurate and sensitive detection method is conducive to the monitoring, control, and removal of PoRVA. In this study, a PoRVA real-time fluorescent reverse transcription recombinase-aided amplification (RT-RAA) assay was developed. Based on the PoRVA VP6 gene, specific primers and probes were designed and synthesized. The sensitivity of RT-RAA and TaqMan probe-based RT-qPCR was 7 copies per reaction and 5 copies per reaction, respectively. The sensitivity of the RT-RAA method was close to TaqMan probe-based RT-qPCR. The detection results of RT-RAA and TaqMan probe-based quantitative real-time RT-PCR methods were completely consistent in 241 clinical samples. Therefore, we successfully established a rapid and specific RT-RAA diagnostic method for PoRVA.

Modelling damped acoustic waves by a dissipation-preserving conformal symplectic method.

We propose a novel stable and efficient dissipation-preserving method for acoustic wave propagations in attenuating media with both correct phase and amplitude. Through introducing the conformal multi-symplectic structure, the intrinsic dissipation law and the conformal symplectic conservation law are revealed for the damped acoustic wave equation. The proposed algorithm is exactly designed to preserve a discrete version of the conformal symplectic conservation law. More specifically, two subsystems in conjunction with the original damped wave equation are derived. One is actually the conservative Hamiltonian wave equation and the other is a dissipative linear ordinary differential equation (ODE) system. Standard symplectic method is devoted to the conservative system, whereas the analytical solution is obtained for the ODE system. An explicit conformal symplectic scheme is constructed by concatenating these two parts of solutions by the Strang splitting technique. Stability analysis and convergence tests are given thereafter. A benchmark model in homogeneous media is presented to demonstrate the effectiveness and advantage of our method in suppressing numerical dispersion and preserving the energy dissipation. Further numerical tests show that our proposed method can efficiently capture the dissipation in heterogeneous media.

Simultaneous temperature and magnetization transfer (MT) monitoring during high-intensity focused ultrasound (HIFU) treatment: preliminary investigation on ex vivo porcine muscle.

PURPOSE: To measure temperature change and magnetization transfer ratio (MTR) simultaneously during high-intensity focused ultrasound (HIFU) treatment. MATERIALS AND METHODS: This study proposed an interleaved dual gradient-echo technique to monitor the heat and tissue damage brought to the heated tissue. The technique was applied to tissue samples to test its efficacy. RESULTS: Ex vivo experiments on the porcine muscle demonstrated that both temperature changes and MTR exhibited high consistency in localizing the heated regions. As the heat dissipated after the treatment, the temperature of the heated regions decreased rapidly but MTR continued to be elevated. Moreover, thermal dose (TD) maps derived from the temperature curves demonstrated a sharp margin in the heated regions, but MTR maps may show a spatial gradient of tissue damage, suggesting complimentary information provided by these two measures. CONCLUSION: In a protocol of spot-by-spot heating over a large volume of tissue, MTR provides additional values to mark the locations of previously heated regions. By continuously recording the locations of heated spots, MTR maps could help plan the next target spots appropriately, potentially improving the efficiency of HIFU treatment and reducing undesirable damage to the normal tissue.