Abstract Background Mitochondria are considered a primary intracellular site of reactive oxygen species (ROS) generation. Generally, cancer cells with mitochondrial genetic abnormalities (copy number change and mutations) have escalated ROS levels compared to normal cells. Since high levels of ROS can trigger apoptosis, treating cancer cells with low doses of mitochondria-targeting / ROS-stimulating agents may offer cancer-specific therapy. This study aimed to investigate how baseline ROS levels might influence cancer cells’ response to ROS-stimulating therapy. Methods Four cancer and one normal cell lines were treated with a conventional drug (cisplatin) and a mitochondria-targeting agent (dequalinium chloride hydrate) separately and jointly. Cell viability was assessed and drug combination synergisms were indicated by the combination index (CI). Mitochondrial DNA copy number (MtDNAcn), ROS and mitochondrial membrane potential (MMP) were measured, and the relative expression levels of the genes and proteins involved in ROS-mediated apoptosis pathways were also investigated. Results Our data showed a correlation between the baseline ROS level, mtDNAcn and drug sensitivity in the tested cells. Synergistic effect of both drugs was also observed with ROS being the key contributor in cell death. Conclusions Our findings suggest that mitochondria-targeting therapy could be more effective compared to conventional treatments. In addition, cancer cells with low levels of ROS may be more sensitive to the treatment, while cells with high levels of ROS may be more resistant. This study provides an insight into understanding the influence of intracellular ROS on drug sensitivity, and may lead to the development of new therapeutic strategies to improve efficacy of anticancer therapy.
Abstract Background Mitochondria are considered a primary intracellular site of reactive oxygen species (ROS) generation. Generally, cancer cells with mitochondrial genetic abnormalities (copy number change and mutations) have escalated ROS levels compared to normal cells. Since high levels of ROS can trigger apoptosis, treating cancer cells with low doses of mitochondria-targeting / ROS-stimulating agents may offer cancer-specific therapy. This study aimed to investigate how baseline ROS levels might influence cancer cells’ response to ROS-stimulating therapy. Methods Four cancer and one normal cell lines were treated with a conventional drug (cisplatin) and a mitochondria-targeting agent (dequalinium chloride hydrate) separately and jointly. Cell viability was assessed and drug combination synergisms were indicated by the combination index (CI). Mitochondrial DNA copy number (mtDNAcn), ROS and mitochondrial membrane potential (MMP) were measured, and the relative expression levels of the genes and proteins involved in ROS-mediated apoptosis pathways were also investigated. Results Our data showed a correlation between the baseline ROS level, mtDNAcn and drug sensitivity in the tested cells. Synergistic effect of both drugs was also observed with ROS being the key contributor in cell death. Conclusions Our findings suggest that mitochondria-targeting therapy could be more effective compared to conventional treatments. In addition, cancer cells with low levels of ROS may be more sensitive to the treatment, while cells with high levels of ROS may be more resistant. Doubtlessly, further studies employing a wider range of cell lines and in vivo experiments are needed to validate our results. However, this study provides an insight into understanding the influence of intracellular ROS on drug sensitivity, and may lead to the development of new therapeutic strategies to improve efficacy of anticancer therapy.
Abstract Background Mitochondria are considered a primary intracellular site of reactive oxygen species (ROS) generation. Generally, cancer cells with mitochondrial genetic abnormalities (copy number change and mutations) have escalated ROS levels compared to normal cells. Since high levels of ROS can trigger apoptosis, treating cancer cells with low doses of mitochondria-targeting / ROS-stimulating agents may offer cancer-specific therapy. This study aimed to investigate how baseline ROS levels might influence cancer cells’ response to ROS-stimulating therapy. Methods Four cancer and one normal cell lines were treated with a conventional drug (cisplatin) and a mitochondria-targeting agent (dequalinium chloride hydrate) separately and jointly. Cell viability was assessed and drug combination synergisms were indicated by the combination index (CI). Mitochondrial DNA copy number (MtDNAcn), ROS and mitochondrial membrane potential (MMP) were measured, and the relative expression levels of the genes and proteins involved in ROS-mediated apoptosis pathways were also investigated. Results Our data showed a correlation between the baseline ROS level, mtDNAcn and drug sensitivity in the tested cells. Synergistic effect of both drugs was also observed with ROS being the key contributor in cell death. Conclusions Our findings suggest that mitochondria-targeting therapy could be more effective compared to conventional treatments. In addition, cancer cells with low levels of ROS may be more sensitive to the treatment, while cells with high levels of ROS may be more resistant. Doubtlessly, further studies employing a wider range of cell lines and in vivo experiments are needed to validate our results. However, this study provides an insight into understanding the influence of intracellular ROS on drug sensitivity, and may lead to the development of new therapeutic strategies to improve efficacy of anticancer therapy.
Abstract Background Mitochondria are considered a primary intracellular site of reactive oxygen species (ROS) generation. Generally, cancer cells with mitochondrial genetic abnormalities (copy number change and mutations) have escalated ROS levels compared to normal cells. Since high levels of ROS can trigger apoptosis, treating cancer cells with low doses of mitochondria-targeting / ROS-stimulating agents may offer cancer-specific therapy. This study aimed to investigate how baseline ROS levels might influence cancer cells’ response to ROS-stimulating therapy. Methods Four cancer and one normal cell lines were treated with a conventional drug (cisplatin) and a mitochondria-targeting agent (dequalinium chloride hydrate) separately and jointly. Cell viability was assessed and drug combination synergisms were indicated by the combination index (CI). Mitochondrial DNA copy number (mtDNAcn), ROS and mitochondrial membrane potential (MMP) were measured, and the relative expression levels of the genes and proteins involved in ROS-mediated apoptosis pathways were also investigated. Results Our data showed a correlation between the baseline ROS level, mtDNAcn and drug sensitivity in the tested cells. Synergistic effect of both drugs was also observed with ROS being the key contributor in cell death. Conclusions Our findings suggest that mitochondria-targeting therapy could be more effective compared to conventional treatments. In addition, cancer cells with low levels of ROS may be more sensitive to the treatment, while cells with high levels of ROS may be more resistant. Doubtlessly, further studies employing a wider range of cell lines and in vivo experiments are needed to validate our results. However, this study provides an insight into understanding the influence of intracellular ROS on drug sensitivity, and may lead to the development of new therapeutic strategies to improve efficacy of anticancer therapy.
Abstract Background: Solute carrier family 25 member 24 (SLC25A24) is a member of the mitochondrial solute vector (MSC) protein superfamily. More and more evidence suggested that SLC family members play an extremely important role in cancers. However, the biological function of SLC25A24 in colorectal cancer has not been reported. Methods: TCGA, GEO, UALCAN, Sangebox3.0 and TIDE databases were used to analyze SLC25A24 in colorectal cancer. The expression of SLC25A24 in 83 pairs of colorectal cancer tissues was detected by immunohistochemistry. qRT-PCR, Western blotting and apoptosis assays were used to explore the biological function of SLC25A24 in colorectal cancer. Results: Through analysis of multiple databases, we found that SLC25A24 expression was higher in colorectal cancer than in adjacent normal tissues, and higher expression of SLC25A24 had a better prognosis. This was verified by clinical case analysis. In addition, based on multiple algorithms of immune infiltration, we found that SLC25A24 was significantly associated with immune infiltration in colorectal cancer. SLC25A24 was significantly associated with clinicopathological features in 83 patients with colorectal cancer. Importantly, SLC25A24 knockdown significantly promoted the apoptosis ability of colorectal cancer cells. In addition, we also found that lower expression of SLC25A24 was associated with poor prognosis and low immunotherapy sensitivity in patients with colorectal cancer. Therefore, SLC25A24 might be a biomarker for the treatment of colorectal cancer. Conclusion: In summary, we found that SLC25A24 was higher expression in colorectal cancer than in adjacent normal tissues, and higher expression of SLC25A24 had a better prognosis. Importantly, we found that SLC25A24 inhibited apoptosis of colorectal cancer cells. In addition, SLC25A24 was associated with immune infiltration of colorectal cancer. Patients with lower expression of SLC25A24 were more prone to immune escape, while patients with higher expression of SLC25A24 were more conducive to immunotherapy. These results suggested that SLC25A24 might be a potential therapeutic target for patients with colorectal cancer.
Rhinovirus (RV) is the most common respiratory virus affecting humans. The majority of asthma deteriorations are triggered by RV infections. However, whether the effects of RV single‑ and double‑stranded RNA on asthma deterioration have common target genes needs to be further studied. In the present study, two datasets (GSE51392 and GSE30326) were used to screen for common differentially expressed genes (cDEGs). The molecular function, signaling pathways, interaction networks, hub genes, key modules and regulatory molecules of cDEGs were systematically analyzed using online tools such as Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, STRING and NetworkAnalyst. Finally, the hub genes STAT1 and IFIH1 were verified in clinical samples using reverse transcription‑quantitative PCR (RT‑qPCR). A total of 85 cDEGs were identified. Function analysis revealed that cDEGs served an important role in the innate immune response to viruses and its regulation. Signal transducer and activator of transcription 1 (STAT1), interferon induced with helicase C domain 1 (IFIH1), interferon regulatory factor 7 (IRF7), DExD/H box helicase 58 (DDX58) and interferon‑stimulating gene 15 (ISG15) were detected to be hub genes based on the protein‑protein interactions and six topological algorithms. A key module involved in influenza A, the Toll‑like receptor signaling pathway, was identified using Cytoscape software. The hub genes were regulated by GATA‑binding factor 2 and microRNA‑146a‑5p. In addition, RT‑qPCR indicated that the expression levels of the hub genes STAT1 and IFIH1 were low during asthma deterioration compared with post‑treatment recovery samples. The present study enhanced the understanding of the mechanism of RV‑induced asthma deterioration.
Online teaching has been confirmed as an effective method for maintaining educational quality in many courses. However, it remains unclear whether the teaching effectiveness of face-to-face teaching can be achieved in neurosurgery clinical courses. In this study, we aim to analyze the effect of online teaching on neurosurgery by comparing it with traditional face-to-face teaching and investigating the students' willingness to engage with online teaching, as well as their evaluations of this mode of teaching. We randomly selected three classes of fourth year medical students who received online teaching and three classes of fourth year medical students who received face-to-face teaching. After completing the neurosurgery curriculum, the study examined the differences between the two groups in terms of satisfaction with the course, theoretical knowledge, and clinical practice abilities, which included medical history inquiry, physical examination, diagnosis, and treatment. In the online teaching setting, a survey was conducted to assess the students' willingness to accept online teaching and to identify its shortcomings. The self-evaluation items included learning motivation, learning more targeted and more interestingly, clinical thinking ability, clinician-patient communication skills, and teamwork skills. All of these aspects were significantly better in the face-to-face group compared to the online group. Each item's score for clinical practice abilities in the face-to-face group was notably higher than that of the online group. Students' satisfaction with and evaluation of the effectiveness of online teaching were lower than those of face-to-face teaching. The primary drawback of online teaching is the lack of a traditional classroom atmosphere, followed by limited interaction with teachers and classmates. The face-to-face group had better self-evaluation and clinical practice abilities than the online group. Additionally, students expressed a preference for face-to-face teaching of neurosurgery clinical courses. The absence of a traditional classroom atmosphere is the main drawback of online teaching. Therefore, online teaching cannot completely replace traditional face-to-face teaching in neurosurgery clinical courses.
Objective: Remote site delayed extradural hematoma (RDEDH) is an uncommon but serious complication that can occur after decompressive craniectomy (DC) in patients with traumatic brain injury (TBI). This study aims to clarify the incidence, predictors, clinical and radiological characteristics, and outcomes of RDEDH to improve the authors' understanding and management of this complication. Methods: This study identified 36 patients with TBI who developed RDEDH after DC. The incidence, predictors, clinical and radiological characteristics, and outcomes were analyzed retrospectively. Continuous variables were compared using the student t test, whereas categorical variables were assessed using the χ 2 test. Variables with a P value of <0.05 in univariable analysis were included in the multivariable logistic regression analysis. Results: The incidence of RDEDH after DC was 14.6%. Preoperative pupillary dilation [bilaterally; odds ratio (OR): 8.797; 95% CI: 1.969–39.297; P = 0.004], intraoperative acute brain swelling (OR: 33.696; 95% CI: 5.073–227.005; P < 0.001), and pupillary abnormalities after DC (OR: 8.141; 95% CI: 2.117–31.307; P = 0.002) were identified as independent risk factors for the development of RDEDH after DC. The average length of hospitalization in the RDEDH group was significantly longer than that in the non-RDEDH group ( P = 0.018). The Glasgow Outcome Scale score at 6 months in the RDEDH group was significantly lower than that in the non-RDEDH group ( P = 0.01). The incidence of poor prognosis in the RDEDH group (80.6%) was significantly higher than that in the non-RDEDH group (59.8%; P = 0.017). Conclusion: Preoperative bilateral pupillary dilation, intraoperative brain swelling, and pupillary abnormalities after surgery were independent risk factors for the development of RDEDH after DC in patients with TBI. The occurrence of RDEDH in patients with TBI after DC did not significantly increase mortality, it was associated with a prolonged length of stay and an increased incidence of poor prognosis.
Based on network pharmacology (NP), the effects of curculigo orchioides (CO) granules alone or CO granules along with tamoxifen on the proliferation and apoptosis (P&A) of human breast cancer (BC) cells were explored. A search database was constructed to obtain the active components (ACs) of CO and related target genes to perform disease mapping, and a BC target map was constructed to perform related pathway enrichment analysis (PEA). The blank control group (CG), estrogen group (EG), and tamoxifen group (TG) were set as controls to observe the effects of CO granules alone and CO granules along with tamoxifen. The PEA showed that the effect of CO on BC may be related to the cooperation of its ACs. The target of action may be related to cell cycle and proliferation, growth factors, metabolic pathways, etc. Different concentrations of CO had different effects, CO granules of various concentrations had no obvious growth-promoting effect ( P < 0.05), and so did CO combined with tamoxifen ( P > 0.05); high-dose (H-D) CO combined with tamoxifen can induce cell apoptosis ( P < 0.05). Through NP, the ACs of CO and related targets of BC were predicted and analyzed. At the same time, it was proved that CO granules are safe in clinical use, and the combined effect of tamoxifen is better in the treatment of estrogen-positive patients, providing reference for the follow-up use of CO in the treatment of BC.
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