Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are being wildly used as target therapy in non-small-cell lung cancer (NSCLC). However, NSCLC patients with wild-type EGFR and KRAS mutation are primary resistant to EGFR-TKIs such as gefitinib. Curcumin has been known as a potential therapeutic agent for several major human cancers. In this study, we investigated the effect of curcumin on the reversal of gefitinib resistance in NSCLC cells as well as their molecular bases. H157 (wild-type EGFR and KARS mutation) and H1299 (wild-type EGFR and HRAS mutation) cells were treated with gefitinib or curcumin alone, or the two combination, and then cell viability, EGFR activity, expressions of Sp1 and Sp1-dependent proteins and receptor tyrosine kinases, markers of autophagy and apoptosis were examined by using CCK-8, colony formation, immunoblot, quantitative PCR, immunofluoscence, and flow cytometry assays. Also xenograft experiments were conduced to test the synergism of curcumin to gefitinib. Our results showed that curcumin significantly enhanced inhibitory effect of gefitinib on primary gefitinib-resistant NSCLC cell lines H157 and H1299. Combination treatment with curcumin and gefitinib markedly downregulated EGFR activity through suppressing Sp1 and blocking interaction of Sp1 and HADC1, and markedly suppressed receptor tyrosine kinases as well as ERK/MEK and AKT/S6K pathways in the resistant NSCLC cells. Meanwhile, combination treatment of curcumin and gefitinib caused dramatic autophagy induction, autophagic cell death and autophagy-mediated apoptosis, compared to curcumin or gefitinib treatment alone, as evidenced by the findings that curcumin and gefitinib combination treatment-produced synergistic growth inhibition and apoptosis activation can be reversed by pharmacological autophagy inhibitors (Baf A1 or 3-MA) or knockdown of Beclin-1 or ATG7, also can be partially returned by pan-caspase inhibitor (Z-VAD-FMK) in H157 and H1299 cells. Xenograft experiments in vivo yielded similar results. These data indicate that the synergism of curcumin on gefitinib was autophagy dependent. Curcumin can be used as a sensitizer to enhance the efficacy of EGFR-TKIs and overcome the EGFR-TKI resistance in NSCLC patients with wild-type EGFR and/or KRAS mutation.

Obstructive sleep apnea‐hypopnea syndrome (OSAHS) is a sleep‐related respiratory disorder that poses a global threat to human health. Chronic intermittent hypoxia (CIH) is its main pathological feature. With the advancements in medical research, the study of CIH‐induced neural injury has gained increasing attention. Studies have shown that CIH can lead to or aggravate neuroinflammation and apoptosis by increasing blood–brain barrier (BBB) permeability, promoting oxidative stress, activating glial cells, and triggering multiple signaling pathways, ultimately resulting in neural injury. These processes contribute to the development of Alzheimer's disease, Parkinson's disease, and stroke. This review aims to summarize the progress in CIH‐induced neural injury and explore various underlying mechanisms, with the goal of providing new insights for the development of therapeutic interventions targeting CIH‐related neural damage.

Drug degradation poses a significant challenge in the pursuit of effective gene therapies for cancers. Here we have developed a bioactive nanosized composite that utilizes human umbilical cord mesenchymal stem cells (hucMSCs) derived small extracellular vesicles (sEVs), to carry tumor suppressor miR-145 alongside erbium-doped rare earth nanoparticles (ErNPs). This approach not only enhances in vivo delivery but also facilitates real-time fluorescence tracking of nucleic acid drugs in the near infrared (NIR) II window. With this technique, we are able to realize and visualize the effective inhibition of colorectal cancer (CRC) progression in a xenografted murine model. Our results revealed that the efficient loading of miR-145 into sEVs could be achieved through a dynamic combination of sonication and electroporation. The resulting miR-145-encapsulated sEVs (i.e., miRNA@sEVs) exhibited a profound ability to hinder tumor growth by effectively downregulating the expression of fascin actin-bundling protein 1 (FSCN1), both in vitro and in vivo. Additionally, the circulation half-time of miRNA@sEVs was measured to be ~ 4 h and the fluorescence at the tumor sites reached a peak intensity at ~ 8 h after intravenous injection of sEVs particles. Finally, the fluorescent signals of miRNA@sEVs were predominantly localized in the mouse liver and spleen, with substantial accumulation in tumors. Our results illuminated the excellent biosafety of miRNA@sEVs and their high accumulation in tumors, leading to efficient suppression of tumor progression. This research heralds a promising advancement in gene therapy, paving the way for more effective and safer treatment options. Not applicable.

Background: Hypoxia contributes to the proliferation, migration, and chemotherapy resistance of lung adenocarcinoma (LUAD). This study aimed to identify hypoxia-related genes (HRGs) in LUAD that were positively correlated with hypoxia-inducible factor 1 alpha (HIF1A), to advance the diagnosis and treatment of this specific type of cancer. Methods: The transcriptome data were retrieved from the Gene Expression Omnibus (GEO). Multiple bioinformatics analysis methods were employed to identify HRGs that were upregulated in LUAD samples and positively correlated with the expression of HIF1A. Machine Learning algorithms were utilized for optimized selection, filtering out core HRGs highly associated with the disease. Finally, in vitro experiments confirmed the expression of these core HRGs in LUAD cells under hypoxic conditions. Results: The study revealed five core HRGs that exhibit a positive correlation with HIF1A [collagen type I alpha 1 chain (COL1A1), interleukin 11 (IL11), matrix metallopeptidase 14 (MMP14), notch receptor 3 (NOTCH3), and thymocyte differentiation antigen 1 (THY1)]. In vitro experiments conducted on A549 cells demonstrated a marked increase in mRNA expression for both the identified core HRGs and HIF1A following chronic intermittent hypoxia (CIH) treatment. The developed model exhibits substantial predictive efficacy for assessing the prognosis of LUAD patients experiencing concurrent hypoxia. Conclusions: The five HRGs that we have identified as positively associated with HIF1A may serve as crucial targets for promoting the progression of LUAD under hypoxic conditions. This discovery offers valuable insights into the diagnosis and treatment of clinical hypoxic disease in patients with LUAD.