Three-Dimensional Bioprinting of Strontium-Modified Controlled Assembly of Collagen Polylactic Acid Composite Scaffold for Bone Repair.

In recent years, the incidence of bone defects has been increasing year by year. Bone transplantation has become the most needed surgery after a blood transfusion and shows a rising trend. Three-dimensional-printed implants can be arbitrarily shaped according to the defects of tissues and organs to achieve perfect morphological repair, opening a new way for non-traumatic repair and functional reconstruction. In this paper, strontium-doped mineralized collagen was first prepared by an in vitro biomimetic mineralization method and then polylactic acid was homogeneously blended with the mineralized collagen to produce a comprehensive bone repair scaffold by a gas extrusion 3D printing method. Characterization through scanning electron microscopy, X-ray diffraction, and mechanical testing revealed that the strontium-functionalized composite scaffold exhibits an inorganic composition and nanostructure akin to those of human bone tissue. The scaffold possesses uniformly distributed and interconnected pores, with a compressive strength reaching 21.04 MPa. The strontium doping in the mineralized collagen improved the biocompatibility of the scaffold and inhibited the differentiation of osteoclasts to promote bone regeneration. This innovative composite scaffold holds significant promise in the field of bone tissue engineering, providing a forward-thinking solution for prospective bone injury repair.

Gasless endoscopic transaxillary subcutaneous mastectomy and immediate reconstruction with implants (GETSMIRI) for breast cancer: Lei's five-step method.

Background: Endoscopic nipple-sparing mastectomy (E-NSM) is a promising procedure in the treatment of breast cancer, but the limitations of endoscopic tools and intrinsic technical complexity of the technique hinder its applicability. Here, we introduce a novel surgery, gasless endoscopic transaxillary subcutaneous mastectomy and immediate reconstruction with implants (GETSMIRI), for breast cancer. and early effects. Methods: A retrospective analysis of the clinical data of 11 female patients, aged 50 (27-78) years, admitted to our hospital from January to December 2022, who underwent gasless endoscopic transaxillary subcutaneous mastectomy and immediate reconstruction with implants (GETSMIRI), was conducted. This study was designed to assess patient satisfaction before and after breast reconstruction, early complications, and breast function. Results: The tumors were all solitary, with a mean maximum diameter of 1.0 (0-2.0) cm and a mean distance of 2.3 (2-4) cm from the nipple, the mean intraoperative bleeding volume was 47.5 mL, and the mean hospital stay was 1.5 d. Postoperatively, 1 patient developed depigmentation of the nipple due to mild ischemia. There were no incisional complications, subcutaneous emphysema, infection, areola necrosis, skin flap necrosis, or removal of the prosthesis and/or patch. No tumor recurrence or metastasis was observed during the follow-up period. The difference between breast satisfaction and psychosocial health scores was not statistically significant (P = 0.680; P = 0.612). Conclusion: GETSMIRI, immediate implantable breast reconstruction, is less invasive than other such procedures, and short-term follow-up results show good postoperative satisfaction, making it an alternative surgical method.

Core-Shell Au@Pd Bimetallic Nanozyme Mediated Mild Photothermal Therapy through Reactive Oxygen Species-Regulating Tumor Thermoresistance.

Mild photothermal therapy (mPTT), which circumvents the limitations of conventional photothermal therapy, is emerging and exhibits remarkable potential in clinical applications. Nevertheless, mPTT is not able to efficiently eradicate tumors because its therapeutic efficacy is dramatically diminished by stress-induced heat shock proteins (HSP). Herein, a core-shell structured Au@Pd (AP) bimetallic nanozyme was fabricated for reactive oxygen species (ROS) augmentation-induced mPTT. The nanocatalytic AP nanozymes with photothermal conversion performance harbor multienzymatic (catalase, oxidase, and peroxidase) activities to induce ROS storm formation. The generated ROS could suppress the heat-defense response of tumor cells by cleaving HSP. Overall, our work highlights a ROS-regulating strategy to counteract hyperthermia-associated resistance in mPTT.

Mild-Photothermal Effect Induced High Efficiency Ferroptosis-Boosted-Cuproptosis Based on Cu2 O@Mn3 Cu3 O8 Nanozyme.

A core-shell-structured Cu2 O@Mn3 Cu3 O8 (CMCO) nanozyme is constructed to serve as a tumor microenvironment (TME)-activated copper ionophore to achieve safe and efficient cuproptosis. The Mn3 Cu3 O8 shell not only prevents exposure of normal tissues to the Cu2 O core to reduce systemic toxicity but also exhibits enhanced enzyme-mimicking activity owing to the better band continuity near the Fermi surface. The glutathione oxidase (GSHOx)-like activity of CMCO depletes glutathione (GSH), which diminishes the ability to chelate Cu ions, thereby exerting Cu toxicity and inducing cuproptosis in cancer cells. The catalase (CAT)-like activity catalyzes the overexpressed H2 O2 in the TME, thereby generating O2 in the tricarboxylic acid (TCA) cycle to enhance cuproptosis. More importantly, the Fenton-like reaction based on the release of Mn ions and the inactivation of glutathione peroxidase 4 induced by the elimination of GSH results in ferroptosis, accompanied by the accumulation of lipid peroxidation and reactive oxygen species that can cleave stress-induced heat shock proteins to compromise their protective capacity of cancer cells and further sensitize cuproptosis. CMCO nanozymes are partially sulfurized by hydrogen sulfide in the colorectal TME, exhibiting excellent photothermal properties and enzyme-mimicking activity. The mild photothermal effect enhances the enzyme-mimicking activity of the CMCO nanozymes, thus inducing high-efficiency ferroptosis-boosted-cuproptosis.

Low-Temperature Photothermal Therapy Platform Based on Pd Nanozyme-Modified Hydrogenated TiO2.

In photothermal treatments (PTTs), normal tissues around cancerous tumors get injured by excessive heat, whereas damaged cancer cells are easily restored by stress-induced heat shock proteins (HSPs) at low temperatures. Therefore, to achieve a unique tumor microenvironment (TME), it is imperative to increase PTT efficiency and reduce normal tissue injury by adopting appropriate reactive oxygen species (ROS) and lipid peroxides (LPO) cross-linked with HSPs. In the present research, a potential strategy for mild photothermal treatments (mPTTs) was proposed by initiating localized catalytic chemical reactions in TME based on Pd nanozyme-modified hydrogenated TiO2 (H-TiO2@Pd). In vitro and in vivo evaluations demonstrated that H-TiO2@Pd had good peroxidase-like activities (POD), glutathione oxidase-like activities (GSHOx), and photodynamic properties and also satisfactory biocompatibility for 4T1 cells. Localized catalytic chemical reactions in H-TiO2@Pd significantly depleted GSH to downregulate the protein expression of GPX4 and promoted the accumulation of LPO and ROS, which consumed HSP70 or inhibited its function in 4T1 cells. Hence, the as-constructed low-temperature photothermal therapeutic platform based on Pd nanozyme-modified H-TiO2 can be a promising candidate to develop a safe and effective mPTT for cancer treatments.

Stromal Interaction Molecule 1-Mediated Store-Operated Calcium Entry Promotes Autophagy Through AKT/Mammalian Target of Rapamycin Pathway in Hippocampal Neurons After Ischemic Stroke.

The pathophysiological process of neuronal injury due to cerebral ischemia is complex among which disturbance of calcium homeostasis and autophagy are two major pathogenesis. However, it remains ambiguous whether the two factors are independent. Stromal interaction molecule 1 (STIM1) is the most important Ca2+ sensor mediating the store-operated Ca2+ entry (SOCE) through interacting with Orai1 and has recently been proven to participate in autophagy in multiple cells. In this study, we aimed to investigate the potential role of STIM1-induced SOCE on autophagy and whether its regulator function contributes to neuronal injury under hypoxic conditions using in vivo transient middle cerebral artery occlusion (tMCAO) model and in vitro oxygen and glucose deprivation (OGD) primary cultured neuron model respectively. The present data indicated that STIM1 induces autophagic flux impairment in neurons through promoting SOCE and inhibiting AKT/mTOR signaling pathway. Pharmacological inhibition of SOCE or downregulation of STIM1 with siRNA suppressed the autophagic activity in neurons. Moreover, stim1 knockdown attenuated neurological deficits and brain damage after tMCAO, which could be reversed by AKT/mTOR pathway inhibitor AZD5363. Together, the modulation of STIM1 on autophagic activation indicated the potential link between Ca2+ homeostasis and autophagy which provided evidence that STIM1 could be a promising therapeutic target for ischemic stroke.

Integrative serum metabolomics and network analysis on mechanisms exploration of Ling-Gui-Zhu-Gan Decoction on doxorubicin-induced heart failure mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Ling-Gui-Zhu-Gan Decoction (LGZGD) formula, derived from traditional Chinese medicine (TCM), has definitive clinical efficacy in the treatment of heart failure (HF) in China. However, little is known of the underlying mechanism of LGZGD. AIM OF THE STUDY: The aim of this work was to investigate the therapeutic mechanism of LGZGD on HF treatment based on an integration of the serum metabolomics and network analysis. MATERIALS AND METHODS: HF model mice were established by intraperitoneal injecting of doxorubicin. Body weight, echocardiography, biochemical assay and hematoxylin and eosin staining experiments were used to evaluate the efficacy of LGZGD. A metabolomics approach based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) was performed to analyze the serum biomarkers from model group, control group and LGZGD-treatment group. Principle component analysis (PCA) and orthogonal projection to latent structures-discriminant analysis (OPLS-DA) were utilized to identify differences of metabolic profiles in mice among the three groups. The network of "gene-enzyme-metabolite" was built to investigate the possible mechanism of LGZGD from the systematic perspective. RESULTS: 54 metabolites, which showed a significantly restoring trend from HF to normal condition, were regarded as potential biomarkers of LGZGD treatment. The most critical pathway was glycerophospholipid metabolism and arachidonic acid metabolism. According to the results of network analysis, 8 biomarkers were regarded as hub metabolites, which meant these metabolites may have a major relationship with the LGZGD therapeutic effects for the HF. 8 enzymes and 29 genes in the network were considered as potential targets of LGZGD treatment. CONCLUSIONS: By integrated serum metabolomic and network analysis, we found that LGZGD might retard the pathological process of HF by regulating the disturbed metabolic pathways and the relative enzymes, which may be potential mechanism for LGZGD in the treatment of HF.