In recent years, the information crosstalk between the central nervous system and the periphery has been a hot topic, such as the brain–gut axis, brain–lung axis, etc. Among them, some studies have shown that brainstem nuclei activity can significantly affect the progression of peripheral tumor; however, regarding lung cancer, our understanding of the basic characteristics of the lung-innervating brain nuclei responsive to lung cancer progression remains deficient. Therefore, we used the pseudorabies virus for retrograde labeling of nerves to study the neural circuits between the lung and brain. We then established a mouse orthotopic lung cancer model and used the expression of the c-Fos gene in brain regions to characterize activated brain circuits and compared these results with those of the control group. We focused on c-Fos activity in nuclei associated with retrograde tracing regions of the brainstem. We found over 16 nuclei in the whole brain with direct or indirect lung innervation through neural retrograde labeling with the pseudorabies virus. We further revealed that the neuronal activity of the rostral ventrolateral reticular nucleus (RVL), caudal nucleus of Raphe (raphe obscurus nucleus, ROb), Raphe pallidus nucleus (RPa), and ventral gigantocellular reticular nucleus (GiV) in the rostral ventromedial and lateral medulla were significantly changed in an orthotopic lung cancer mouse model by the immunostaining of c-Fos early responsive protein. Thus, the distinctive rostroventral medulla area, functionally closely related to the vagus nerve, likely plays a role in central neural interaction with peripheral lung tumors and deserves future investigation.

Morphine has been suggested to affect cancer cell dynamics and decrease survival rates in lung cancer patients at specific doses, but the precise mechanisms poorly understood. In this study, we aimed to investigate the molecular mechanisms by which morphine modulates the malignant characteristics of non-small cell lung cancer. Cell proliferation was assessed via the Cell Counting Kit-8 assay, and cell migration and invasion were examined via wound healing and Transwell assays. We employed immunofluorescence staining to evaluate E-cadherin expression in A549 and Lewis lung cancer (LLC) cell lines and immunohistochemistry to evaluate E-cadherin expression in nude mice tumours. Additionally, the in vivo effects of morphine on lung cancer progression were explored in a xenograft tumour experiments, in which naloxone was used as a morphine antagonist. Western blot analysis was performed to detect E-cadherin, phosphorylated mTOR (p-mTOR), mTOR, phosphorylated AKT (p-AKT), AKT, phosphorylated PI3K (p-PI3K), and PI3K protein levels in A549 and LLC cells as well as in tumour samples. Morphine (10 µM) significantly increased the proliferation of A549 and LLC cells in vitro (p < 0.05). It also enhanced the migratory and invasive capacities of these cell lines (p < 0.01). Mechanistically, morphine treatment (10 µM) led to a reduction in the expression of E-cadherin, and an increase in the phosphorylation of PI3K, AKT, and mTOR in A549 and LLC cells (p < 0.01). Morphine treatment (1.5 mg/kg) also reduced E-cadherin expression in xenograft tumours and promoted tumour growth in vivo (p < 0.05). This effect was reversed by naloxone (0.1 mg/kg). The results demonstrated that morphine stimulates the malignant proliferation of A549 and LLC cell lines and promotes xenograft tumour growth. Perhaps by specifically targeting MOR, morphine triggers a signalling cascade that activates the PI3K/AKT/mTOR pathway while inhibiting the EMT marker E-cadherin, which may consequently promote the progression of lung cancer.

Oridonin(Ori), a natural ent-kaurane diterpenoid derived from the medicinal herb Rabdosia rubescens, has garnered significant interest for its potent anti-inflammatory and immunomodulatory properties. A key mechanism underlying these effects is its ability to regulate polarization. This review elaborates on the multifaceted mechanisms by which Ori modulates macrophage, extending beyond the inhibition of pro-inflammatory signaling pathways. We highlight its emerging role in metabolic reprogramming by shifting the functional balance from a pro-inflammatory M1 phenotype towards an anti-inflammatory and tissue-reparative M2 phenotype. Ori exhibits therapeutic potential not only in cancer and but also in a broad spectrum of other conditions, including non-alcoholic fatty liver disease, rheumatoid arthritis, colitis, asthma, atherosclerosis, and sepsis. However, the clinical translation of Ori is severely hampered by its unfavorable pharmacokinetic properties, such as poor aqueous solubility and low oral bioavailability. We conclude by discussing future perspectives, emphasizing the need for advanced drug delivery systems, the integration of multi-omics technologies to thoroughly map macrophage responses, and the application of network pharmacology and artificial intelligence to propel the rational development of oridonin as a novel macrophage-centric therapeutic agent.

Patients undergoing induced abortion frequently experience acute visceral pain and preoperative anxiety, the latter of which is known to increase anesthetic requirements. This study aimed to determine the median effective dose (ED50) and the 95% effective dose (ED95) of propofol in combination with oxycodone for alleviating visceral pain, specifically testing the finding that anxiety increases the needed propofol dose. Female patients, who were scheduled for elective abortion surgeries, with PAS-7 ≥8 were classified as anxious group (Group A), while those with PAS-7 < 8 were classified as non-anxious group (Group N). Both groups received an intravenous dose of 0.10 mg/kg of oxycodone prior to surgery.And 2 to 3 minutes later, the first patient in the sequence received an initial dose of 3.50 mg/kg of propofol, with subsequent doses determined by Dixon’s up-and-down method. The ED50 (95% CI) for propofol was 1.96 mg/kg (1.87–2.05) in Group N and 2.42 mg/kg (2.30–2.53) in Group A; the ED95 (95% CI) was 2.10 mg/kg (2.03–2.39) and 2.60 mg/kg (2.50–2.95), respectively. The lack of overlap in the 95% confidence intervals indicates a statistically significant difference between groups. The combination of 0.10 mg/kg oxycodone and propofol was effective for visceral pain suppression during artificial abortion. Notably, patients with anxiety required higher doses of propofol to achieve satisfactory pain relief during abortion surgeries. This human study was approved by the Medical Ethics Committee of the People’s Hospital of Qiannan (QNZY-QNYZKYRC-23-0801) and registered at https://www.chictr.org.cn/ (Date: 09/26/2023, ChiCTR2300076169).

Apoptosis undergoes dynamic changes during tumor progression and treatment and has complex effects on tumor development. Apoptotic cell-derived extracellular vesicles (Apo-EVs) have recently been recognized as key mediators of intercellular communication, but their role in hepatocellular carcinoma (HCC) remains unclear. We performed a series of in vitro and in vivo experiments to investigate the effects of tumor-derived Apo-EVs on HCC cell proliferation, apoptosis, and metabolic remodeling. Additional mechanistic studies were conducted to identify the functional cargo molecules carried by Apo-EVs and to determine their roles in ATP synthesis and metabolic regulation. Tumor-derived Apo-EVs suppressed HCC cell proliferation and increased apoptosis. Mechanistically, Apo-EVs promoted apoptotic cell death by shifting cellular metabolism from aerobic glycolysis to oxidative phosphorylation. Notably, transmembrane protein 70 (TMEM70), which is transported by Apo-EVs, was identified as a key mediator of this process. TMEM70 participated in ATP synthesis and contributed to metabolic reprogramming in HCC cells. Our study reveals a potential mechanism by which tumor-derived Apo-EVs promote apoptosis and metabolic remodeling in HCC. Apo-EV-associated TMEM70 may contribute to this process through its involvement in mitochondrial metabolism. These findings suggest that Apo-EVs and selected cargo molecules may represent promising therapeutic targets for HCC.