Cancer-derived exosomal miRNAs are implicated in tumorigenesis and development of lung adenocarcinoma (LUAD). The objective of this study is to unravel the biological function of exosomal miR-197-3p in LUAD metastasis. qRT-PCR showed that elevated miR-197-3p in LUAD tissues was positively correlated with LUAD metastasis. CCK-8, tube formation, transwell and wound healing assays revealed that exosomal miR-197-3p from LUAD cells promoted the proliferation, angiogenesis and migration of HUVECs in vitro. LUAD cells-derived exosomal miR-197-3p also facilitated tumor growth and angiogenesis in LUAD cells-derived tumor xenograft model. TIMP2 and TIMP3 were identified as target genes of miR-197-3p in HUVECs by bioinformatics analysis and luciferase reporter assay. Functional studies illustrated that exosomal miR-197-3p promoted angiogenesis and migration via targeting TIMP2 and TIMP3 in HUVECs. In vivo data further supported that exosomal miR-197-3p promoted lung metastasis via TIMP2/3-mediated angiogenesis. In conclusion, LUAD cells-derived exosomal miR-197-3p conferred angiogenesis via targeting TIMP2/3 in LUAD metastasis.

Lung adenocarcinoma (LUAD) is the main histological type of lung cancer, which is the leading cause of cancer-related deaths. Long non-coding RNAs (lncRNAs) were recently revealed to be involved in various cancers. However, the clinical relevance and potential biological roles of most lncRNAs in LUAD remain unclear. Here, we identified a prognosis-related lncRNA ITGB1-DT in LUAD. ITGB1-DT was upregulated in LUAD and high expression of ITGB1-DT was correlated with advanced clinical stages and poor overall survival and disease-free survival. Enhanced expression of ITGB1-DT facilitated LUAD cellular proliferation, migration, and invasion, and also lung metastasis in vivo. Knockdown of ITGB1-DT repressed LUAD cellular proliferation, migration, and invasion. ITGB1-DT interacted with EZH2, repressed the binding of EZH2 to ITGB1 promoter, reduced H3K27me3 levels at ITGB1 promoter region, and therefore activated ITGB1 expression. Through upregulating ITGB1, ITGB1-DT activated Wnt/β-catenin pathway and its downstream target MYC in LUAD. The expressions of ITGB1-DT, ITGB1, and MYC were positively correlated with each other in LUAD tissues. Intriguingly, ITGB1-DT was found as a transcriptional target of MYC. MYC directly transcriptionally activated ITGB1-DT expression. Thus, ITGB1-DT formed a positive feedback loop with ITGB1/Wnt/β-catenin/MYC. The oncogenic roles of ITGB1-DT were reversed by depletion of ITGB1 or inhibition of Wnt/β-catenin pathway. In summary, these findings revealed ITGB1-DT as a prognosis-related and oncogenic lncRNA in LUAD via activating the ITGB1-DT/ITGB1/Wnt/β-catenin/MYC positive feedback loop. These results implicated ITGB1-DT as a potential prognostic biomarker and therapeutic target for LUAD.

Opioids are the most widely used analgesics and therefore have often been the focus of pharmacological research. Macrophages are the most plastic cells in the hematopoietic system. They show great functional diversity in various organism tissues and are an important consideration for the study of phagocytosis, cellular immunity, and molecular immunology. The expression of opioid receptors in macrophages indicates that opioid drugs act on macrophages and regulate their functions. This article reviewed the collection of research on effects of opioids on macrophage function. Studies show that opioids, both endogenous and exogenous, can affect the function of macrophages, effecting their proliferation, chemotaxis, transport, phagocytosis, expression of cytokines and chemokine receptors, synthesis and secretion of cytokines, polarization, and apoptosis. Many of these effects are closely associated with mitochondrial function and functions of other organelles in macrophages. Therefore, in depth research into effects of opioids on macrophage organelles may lead to some interesting new discoveries. In view of the important role of macrophages in HIV infection and tumor progression, this review also discusses effects of opioids on macrophages in these two pathological conditions.

Jumonji domain-containing protein 6 (JMJD6) is a homolog of hypoxia-inducible factor (HIF) asparaginyl hydroxylase, an inhibitor of HIF. HIF-1α is known to participate in neuropathic pain (NPP) during chronic constriction injury (CCI); however, the roles of JMJD6 in NPP have not been systematically investigated. In this study, we examined the temporal distribution and cellular location of JMJD6 in the spinal cord during CCI. In addition, we assessed behavioral changes representative of NPP in rats. Following CCI, lentiviral vectors (LV-JMJD6) were intrathecally administered to observe the changes in the expression of JMJD6, HIF-1α, and its downstream factor caspase-3. Co-immunoprecipitation was used to detect potential interactions between JMJD6 and HIF-1α. We found that JMJD6 was decreased in rats following CCI, which was accompanied by significant NPP–associated behavioral changes. JMJD6 was mainly expressed in neurons. Intrathecal injection of LV-JMJD6 following CCI alleviated the thermal and mechanical hyperalgesia, normalized JMJD6 protein expression, and decreased HIF-1α protein expression with a corresponding reduction in caspase-3 protein expression. Furthermore, the co-immunoprecipitation analyses showed that JMJD6 and HIF-1α protein immunoprecipitated with each other, indicating an interaction between these two proteins. Taken together, the results suggest that JMJD6 may serve as a sensor in neurons of the adult rat spinal cord during the CCI state. Furthermore, JMJD6 may exert its function in NPP by regulating HIF-1α in rats exposed to CCI.

Background: Acute kidney injury (AKI) is a common postoperative complication, and hypotension may contribute. We therefore tested the primary hypothesis that individualized intraoperative blood pressure regulation reduces postoperative AKI in older surgical patients. Methods: We enrolled patients ≥60 years old scheduled for elective major abdominal surgery with invasive arterial pressure monitoring. All had goal-directed fluid management based on stroke volume variation cardiac output, and administration of a starch. Participants were randomly assigned to: (1) individualized blood pressure management targeting a systolic blood pressure (SBP) within −20% and +10% if baseline SBP was ≥130 mmHg or diastolic blood pressure was ≥80 mmHg, or otherwise, to target SBP within ±10% of the baseline value; (2) maintenance of SBP ≥90 mmHg and MAP ≥65 mmHg. Metaraminol was used to achieve the blood pressure target. AKI incidence was assessed by Kidney Disease Improving Global Outcomes criteria during the initial 7 postoperative days. Results: 192 patients were assigned to individualized (n = 96) or routine (n = 96) pressure management. 179 patients were included in the intention-to-treat analysis. Age averaged 68 ± 5 (SD) years and 64% were male. Randomization to the individualized management reduced the area under MAP <65 mmHg (median difference: −37 [−47 to −25] mmHg-minute, P < 0.001]. The incidence of the AKI was 11% in patients assigned to individualized management vs. 16 % in those assigned to routine management: relative risk 0.72 (95% confidence interval, 0.34–1.54), P = 0.396. Patients assigned to individualized pressure management had more urine output, a shorter postoperative mechanical ventilation duration, and faster recovery of bowel function. Conclusion: Individualized blood pressure management markedly reduced hypotension. As expected in a pilot trial, the 28% reduction in AKI was not statistically significant. However, the reduction was clinically meaningful and suggests that a full trial is warranted.

Mitochondria, known as the powerhouses of cells, are considered a key source of reactive oxygen species (ROS) production in various cell types. In the context of neuropathic and inflammatory pain, both mitochondrial dysfunction and hyperfunction can lead to aberrant production of mitochondrial reactive oxygen species (mtROS), which has been implicated in the development and persistence of pain hyperalgesia. This comprehensive review delves into the compelling correlation between mitochondrial functional activity and diverse pain conditions, with a special emphasis on inflammatory pain and chemotherapy-induced peripheral neuropathy (CIPN). Furthermore, it explores the therapeutic potential of targeting mitochondrial protection and mtROS scavenging to maintain mitochondrial redox homeostasis, offering a novel approach for pain management. The findings presented here provide valuable insights into the multifaceted role of mitochondria in pain modulation, laying a solid foundation for future research and the development of innovative analgesic strategies.