Innovative Biomaterials for Bone Tumor Treatment and Regeneration: Tackling Postoperative Challenges and Charting the Path Forward.

Surgical resection of bone tumors is the primary approach employed in the treatment of bone cancer. Simultaneously, perioperative interventions, particularly postoperative adjuvant anticancer strategies, play a crucial role in achieving satisfactory therapeutic outcomes. However, the occurrence of postoperative bone tumor recurrence, metastasis, extensive bone defects, and infection are significant risks that can result in unfavorable prognoses or even treatment failure. In recent years, there has been significant progress in the development of biomaterials, leading to the emergence of new treatment options for bone tumor therapy and bone regeneration. This progress report aims to comprehensively analyze the strategic development of unique therapeutic biomaterials with inherent healing properties and bioactive capabilities for bone tissue regeneration. These composite biomaterials, classified into metallic, inorganic non-metallic, and organic types, are thoroughly investigated for their responses to external stimuli such as light or magnetic fields, internal interventions including chemotherapy or catalytic therapy, and combination therapy, as well as their role in bone regeneration. Additionally, an overview of self-healing materials for osteogenesis is provided and their potential applications in combating osteosarcoma and promoting bone formation are explored. Furthermore, the safety concerns of integrated materials and current limitations are addressed, while also discussing the challenges and future prospects.

A review of matrix metalloproteinase-2-sensitive nanoparticles as a novel drug delivery for tumor therapy.

Matrix metalloproteinase-2 (MMP-2)-responsive nanodrug vehicles have garnered significant attention as antitumor drug delivery systems due to the extensive research on matrix metalloproteinases (MMPs) within the tumor extracellular matrix (ECM). These nanodrug vehicles exhibit stable circulation in the bloodstream and accumulate specifically in tumors through various mechanisms. Upon reaching tumor tissues, their structures are degraded in response to MMP-2 within the ECM, resulting in drug release. This controlled drug release significantly increases drug concentration within tumors, thereby enhancing its antitumor efficacy while minimizing side effects on normal organs. This review provides an overview of MMP-2 characteristics, enzyme-sensitive materials, and current research progress regarding their application as MMP-2-responsive nanodrug delivery system for anti-tumor drugs, as well as considering their future research prospects. In conclusion, MMP-2-sensitive drug delivery carriers have a broad application in all kinds of nanodrug delivery systems and are expected to become one of the main means for the clinical development and application of nanodrug delivery systems in the future.

Obstructive sleep apnea promotes the progression of lung cancer by modulating cancer cell invasion and cancer-associated fibroblast activation via TGFß signaling.

OBJECTIVE: Obstructive sleep apnea (OSA) is associated with severity of pneumonia; however, the mechanism by which OSA promotes lung cancer progression is unclear. METHODS: Twenty-five lung cancer patients were recruited to investigate the relationship between OSA and cancer-associated fibroblast (CAFs) activation. Lung cancer cells (A549) and WI38 fibroblast cells were used to explore the hypoxia-induced TGFß expression using qPCR, Western blot, and ELISA. Wound healing and transwell assays were performed to evaluate cancer cell migration and invasion. A549 or A549-Luc + WI38 xenograft mouse models were established to detect the intermittent hypoxia (IH) associated with lung tumor growth and epithelial-mesenchymal transition (EMT) in vivo. RESULTS: OSA promotes CAF activation and enrichment in lung cancer patients. Hypoxia (OSA-like treatment) activated TGFß signaling in both lung cancer cells and fibroblasts, which promoted cancer cell migration and invasion, and enriched CAFs. IH promoted the progression and EMT process of lung cancer xenograft tumor. Co-inoculation of lung cancer cells and fibroblast cells could further promote lung cancer progression. CONCLUSIONS: IH promotes lung cancer progression by upregulating TGFß signaling, promoting lung cancer cell migration, and increasing the CAF activation and proportion of lung tumors.

Intermittent hypoxia inhibits anti-tumor immune response via regulating PD-L1 expression in lung cancer cells and tumor-associated macrophages.

Accumulating evidence has shown an increased tumor incidence and reduced survival rate in cancer patients with obstructive sleep apnea (OSA). Although intermittent hypoxia is known to play a crucial role, the molecular mechanism by which intermittent hypoxia accelerates lung cancer progression remains to be elucidated.A lung cancer xenograft mouse model was established by subcutaneously injecting LLC cells into C57BL/6 mice. The tumor-bearing mice were exposed to either normoxia or intermittent hypoxia and received either IgG2a, anti-programmed death ligand-1 (PD-L1), PX-478, or anti-PD-L1 + PX-478 treatment.A significant upregulation of tumor associated macrophages (TAMs) papulation and PD-L1 levels was observed in lung adenocarcinoma patients with OSA. We further confirmed that hypoxia-inducible factor-1 alpha (HIF-1α) regulates PD-L1 at transcriptional levels, mainly through binding to the hypoxia response element 4. Using a lung cancer xenograft mouse model, we observed that intermittent hypoxia exposed tumors grew faster and bigger with upregulated HIF-1α and PD-L1 expression, enhanced TAMs and Treg populations, and reduced cytotoxic T cells and cytokine secretion. Finally, we found a combination of PX-478 and anti-PD-L1 exerted an encouraging tumor inhibition effect compared to single treatment. Combination therapies based on HIF-1α and PD-L1 blockade might serve as a promising strategy to treat lung cancer patients with OSA.

Construction of a MnO2/Crudlan composite hydrogel and its killing effect on melanoma B16-F10 cells combined with photothermal therapy / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：构建负载二氧化锰（MnO2）纳米颗粒的可得然（Cur）复合水凝胶MnO2@Cur（简称MGel），研究其对黑色素瘤B16-F10细胞的杀伤效果。方法：采用热诱导法制备Cur水凝胶（Gel），物理负载MnO2构建MGel，表征其宏观和微观形貌，检测其机械性能、降解性能以及光热转换性能等理化性能，并研究其联合PTT对小鼠皮肤黑色素瘤B16-F10细胞的光热杀伤效果。结果：MGel具有优异的机械和可降解性能，抗拉伸强度达（127.97±3.60）kPa、抗压缩强度达（151.44±5.23）kPa，28 d降解率约58.17%。MGel负载MnO2纳米片（粒径约180 nm）获得优异的光热转换性能，负载1.0 mg/mL MnO2的MGel在1.0 W/cm2的808 nm NIR光照4 min后到达最高温度50 ℃。细胞毒性实验和Calcein-AM/PI荧光双染色实验表明，MGel联合PTT有效杀伤B16-F10黑色素瘤细胞，NIR光照使得MGel组细胞存活率降低至（4.68±0.66）%（P<0.000 1）。结论：MGel复合水凝胶具备优异的机械性能、可降解性能以及光热转换性能，其联合PTT能有效杀伤肿瘤细胞，可能成为一种有效治疗黑色素瘤的新手段。

Association of total cholesterol and atherosclerotic cardiovascular disease in patients with follicular thyroid cancer: A real-world study from Chinese populations.

ABSTRACT: The association between serum total cholesterol (TC) level and incident atherosclerotic cardiovascular disease (ASCVD) in patients with follicular thyroid cancer postthyroidectomy is unknown.This was a retrospective study and patients (n = 384) were divided into low and high TC groups according to the median TC level. Incidence of composite ASCVD (myocardial infarction, ischemic stroke, and cardiovascular death) was compared between these 2 groups and factors contributing to the association of TC and ASCVD were evaluated.Patients in the high TC group were older and more likely to have diabetes and have higher C-reactive protein level. After thyroidectomy, serum levels of free triiodothyronine and free thyroxine were lower while thyroid-stimulating hormone level was higher in the high TC group. 31.6% and 39.7% of patients developed hypothyroidism in the low and high TC groups (P < .05) postthyroidectomy. The incidence rate of composite ASCVD was higher in the high TC versus low TC groups, with incidence rate ratio of 1.69 (95% confidence interval [CI]: 1.07-2.69), which was mainly driven by a higher incidence rate of myocardial infarction in the high TC group (incidence rate ratio: 2.11 and 95% CI: 1.10-4.20). In unadjusted model, higher TC was associated with 73% higher risk of composite ASCVD. After adjustment for hypothyroidism, the association of higher TC and composite ASCVD was attenuated into insignificance, with hazard ratio of 0.92 and 95% CI: 0.81 to 1.34.Increased TC level was associated with composite ASCVD, which might be attributed to hypothyroidism postthyroidectomy. The use of levothyroxine might help to prevent hypercholestemia and reduce the incidence of ASCVD.

Two-stage excitation model of diode pumped rare gas atoms lasers.

Diode pumped rare gas atoms lasers (DPRGLs) are potential candidates of the high-energy lasers, due to the advantages of high laser power and high optical conversion efficiency. In this paper, a two-stage excitation model of DPRGLs is established including gas discharge excitation and semiconductor laser pump to study energy loss mechanism and obtain total efficiency. The results of numerical simulation agree well with those of Rawlins et al.'s experiment. Through parameter optimization, the total efficiency and optical conversion efficiency reach 51.5% and 62.7% respectively, at pump intensity of 50 kW/cm2 and reduced electric field of 8 Td. Parameter optimization of two-stage excitation lasers is theoretically studied, which is significant for the DPRGLs design with high total efficiency.

[Application of single drop microextraction in the determination of phthalate esters and parabens in drugs by gas chromatography-mass spectrometry].

Single drop microextraction (SDME) was used for the determination of phthalate esters and parabens in drugs by gas chromatography-ion trap mass spectrometry (GC-IT/MS). The effects of the nature of extraction solvents, microdrop volume, the depth of microdrop in sample solution, extraction time and stirring rate on the extraction efficiency were investigated separately. The optimal SDME conditions, 1.5 microL of toluene, 0.8 cm of the depth of microdrop, 1 000 r/min of stirring rate and 20 mm of extraction time, were obtained and used for the analysis of methylparaben (MP), ethylparaben (EP), propylparaben (PP), iso-propylparaben (IPP), butylparaben (BP), dimethyl phthalate (DMP), diethyl phthalate (DEP) and dibutyl phthalate (DBP) in drugs. The results showed that the working curves for 8 phthalate esters and parabens were linear in the range of 0.032 - 80 mg/L by GC-MS on selective ion storage mode. The limits of detection (LOD) were between 0.6 microg/L and 1.28 mg/L, the overall recoveries were 95.85% - 148.85% with the relative standard deviations of 3.9% - 14.9%.

[Application of single drop microextraction in the determination of phthalate esters in food by gas chromatography-mass spectrometry].

A novel, simple, fast and environment-friendly method based on single drop microextraction (SDME) was developed for the determination of phthalate esters in food by gas chromatography-mass spectrometry (GC-MS). The effects of the nature of organic solvents, microdrop volume, the depth of microdrop in sample solution, extration time and stirring rate on the extraction efficiency were investigated separately. The optimal SDME conditions, 2.0 microL of toluene, 0.75 cm of the depth of microdrop, 1 000 r/min of stirring rate and 20 min of extraction time, were obtained and used for the analysis of dimethyl phthalate (DMP), diethyl phthalate (DEP), di-n-butyl phthalate (DBP), dioctyl phthalate (DOP) and diethylhexyl phthalate (DEHP) in food. At first, a sample was dissolved with de-ionized water and then extracted with ultrasonication for 15 min. Then, it was filtrated and the solution was extracted and concentrated by a single drop of a solvent. Finally, it was analyzed by GC-MS. The reproducibility, linearity, recovery, and limit of detection of the method were studied. The results showed that the limits of detection (LOD) were between 25 ng/L and 0.8 mg/L. The overall recoveries were 87.1% - 114.4% with the relative standard deviations of 4.9% - 11.6%. This method has been successfully applied to the analysis of food samples.