Sirtuin 3 (SIRT3) is located in the mitochondrial matrix, regulating acetylation levels of metabolic enzymes. As an oncogene or a tumor suppressor gene, SIRT3 plays an important role in the commencement and progression of certain cancers. In this research, we investigated the role of SIRT3 in the progression of nonsmall cell lung carcinoma (NSCLC).
In this study, bioinformatics was used to analyze the differential expression of SIRT3 in NSCLC tissue and normal tissues, prognosis, single-cell analysis, and related signaling pathways. The Lentiviral overexpressing SIRT3 was constructed, and CCK8 and colony formation assay were used to evaluate the NSCLC cells proliferation, ROS production was detected by flow cytometry, and the sea-horse test was used to measure cellular oxygen consumption (OCR).
SIRT3 expression was significantly decreased in NSCLC, and low expression of SIRT3 was closely related to the poor prognosis. Besides, on the whole, upregulation of SIRT3 suppressed cell proliferation in A549 and SK-MES-1 cells via increasing oxidative phosphorylation (OXPHOS) and ROS production.
Overall, our findings suggested that SIRT3 functions as a tumor suppressor that can suppress the progression of NSCLC via stimulating ROS production.
Small cell lung cancer (SCLC) is one of the most lethal malignancies worldwide. This study aimed to examine the clinical benefits of new systemic therapies derived from randomized controlled trials (RCTs) published from 2002 to 2023 based on the magnitude of clinical benefit scale developed by the European Society for Medical Oncology (ESMO-MCBS).
We searched PubMed for Phase 3 RCTs on systemic therapy for SCLC published between January 2002 and December 2023. Therapeutic benefit was graded from 5 to 1 according to the ESMO-MCBS framework, with a score of 4 or 5 representing a meaningful clinical benefit. The statistical power of the trial design was also assessed using ESMO-MCBS.
Sixty-four RCTs with 23 683 participants were eligible for inclusion. The number of RCTs related to molecular targeted therapy or immunotherapy has increased over the years. Among the 62 RCTs for which statistical power could be evaluated, 38 (61.3%) were designed to identify an effect size that would meet the ESMO-MCBS benefit threshold and were less likely to investigate second- or subsequent-line treatment (15.8% vs. 50.0%, p = 0.004), have noninferiority design (0% vs. 25.0%, p = 0.002) and set PFS (0% vs. 16.7%) or response rate (0% vs. 16.7%) as the only primary endpoint (p = 0.002). The ESMO-MCBS framework was applied in 29 RCTs reporting positive results, and only 8 (27.6%) met the threshold for a clinical benefit. The RCTs designed to detect differences that would meet the thresholds were more likely to demonstrate meaningful clinical benefit (87.5% vs. 50.0%, p = 0.099).
Most positive SCLC-RCTs did not meet the ESMO-MCBS threshold for meaningful clinical benefits. Strict power calculations should be adopted in the design of future RCTs.
Dynamic hyperinflation in chronic obstructive pulmonary disease (COPD) results in intrinsic positive end-expiratory pressure (auto-PEEP). Automatic tube compensation (ATC) is used to increase airway pressure in COPD and overcome endotracheal tube (ETT)–imposed respiratory workload. We aim to investigate effects of ATC activation on auto-PEEP decrease in COPD.
ATC was activated three times a day (1 min duration) in the morning, evening, and night shift. Auto-PEEP was measured for the 1 min period (every 6 s) following ATC activation. Linear mixed model (LMM) was used to measure changes in auto-PEEP and compare with baseline value. Age, gender, and COPD types were inserted in model as covariates and analyzed using SPSS.
A total of 60 patients including COPD (n = 40) and COPD with exacerbation (n = 20) were included. Compared with exacerbated COPD, baseline auto-PEEP in COPD was significantly lower in morning (p = 0.011), evening (p = 0.043), and night shift (p = 0.007). After ATC activation, auto-PEEP decreased significantly in COPD in morning, evening, and night (p = 0.001), but magnitude of this decrease was notably larger in COPD than in exacerbated COPD (p = 0.001). Moreover, there was a significant relationship between COPD exacerbation and changes in auto-PEEP in morning (β = −0.27, p = 0.001), evening (β = −0.16, p = 0.001), and night (β = −0.26, p = 0.001).
The activation of ATC mode in COPD patients under mechanical ventilation could decrease the value of auto-PEEP. Nevertheless, COPD patients with an exacerbation appear to benefit less from ATC activation.
This study aimed to identify a specific SCLC population that would benefit from surgery.
This study utilized patient data retrieved from the Surveillance, Epidemiology, and End Results (SEER) database spanning 2010 to 2017. To mitigate clinical biases, the propensity score matching (PSM) technique was employed. Separate cohorts were aligned using PSM according to the AJCC 8th edition TNM classification. The Kaplan–Meier method and a competing risk model were applied to evaluate overall survival (OS) and lung cancer–specific survival (LCSS), respectively.
Among the 3394 patients with potentially resectable SCLC included in the study, 3062 underwent chemoradiotherapy and 332 underwent surgical treatment with adjuvant chemotherapy. Surgery was associated with better OS (median OS: 49 months; 95% CI: 35–63 months vs. 27 months; 95% CI: 21–33 months, p < 0.001) and LCSS (SHR, 0.578; 95% CI: 0.411–0.815, p < 0.001) in stage I patients after PSM. However, there was no significant difference in OS and LCSS between the surgery and nonsurgery groups in stage II and III patients after PSM. In the entire cohort, lobectomy was associated with improved OS (median OS: 48.6 vs. 28.7 months, p < 0.0001), but not LCSS (SHR, 0.696; 95% CI: 0.466–1.040, p = 0.078) compared with sublobar resection after PSM.
Surgery with adjuvant chemotherapy significantly improved the survival prognosis of patients with early-stage SCLC. However, surgical treatment should be carefully considered in patients with stage II/III disease. Lobectomy is oncologically equal to sublobar resection.
This study systematically analyzes the relationship of vitamin A on the neonatal respiratory diseases. An extensive literature search for relevant studies was conducted on PubMed, Web of Science, and so on. After screening in strict accordance with the inclusion and exclusion criteria, 12 articles on vitamin A deficiency and 12 articles on vitamin A supplementation were included. Stata 17.0 software was used to perform meta-analysis, heterogeneity test, and sensitivity analysis, and the corresponding mathematical model was used to merge the data. The meta-analysis results of the relationship between vitamin A deficiency and neonatal respiratory diseases indicated that compared with the neonates with normal vitamin A, the neonates with vitamin A deficiency had adverse health outcomes of neonatal respiratory diseases (OR = 4.86, 95% CI: 2.68–8.84), of which neonatal respiratory distress syndrome (NRDS) (OR = 4.10, 95% CI: 2.32–7.23) and neonatal pneumonia (OR = 3.22, 95% CI: 2.18–4.77) were analyzed by subgroup analysis. The meta-analysis of the relationship between vitamin A supplementation therapy and neonatal respiratory diseases showed that vitamin A supplementation was an effective therapeutic measure for neonatal respiratory diseases (RR = 1.06, 95% CI: 1.04–1.07): NRDS (RR = 1.03, 95% CI: 1.02–1.05) and NBPD (RR = 1.08, 95% CI: 1.01–1.15). The funnel chart method results show that there was publication bias in studies on vitamin A deficiency induced to and vitamin A supplementation therapy for neonatal respiratory diseases. The sensitivity analysis results showed that excluding some special article had some effect on the final pooled effect. But generally speaking, the result of meta-analysis was stable. There is a statistical correlation of vitamin A on the neonatal respiratory diseases from two aspects of etiological exploration and effect evaluation of treatment.
Exosomes have been established to be enriched with various long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) that exert various biological effects. However, the lncRNA- and circRNA-mediated coexpression competing endogenous RNA (ceRNA) regulatory network in exosomes derived from the plasma of patients with lung adenocarcinoma (LUAD) remains elusive.
This study enrolled nine patients with lung adenocarcinoma and three healthy individuals, and the differential expression of messenger RNAs (mRNAs), lncRNAs, and circRNAs was detected using microarray analysis, while microRNAs (miRNAs) were detected through RNA sequencing. Additionally, bioinformatics algorithms were applied to evaluate the lncRNA–miRNA–mRNAs/circRNA–miRNA–mRNA network. Differentially expressed cicRNAs were identified via quantitative reverse transcription polymerase chain reaction (RT-qPCR). A total of 1016 lncRNAs, 1396 circRNAs, 45 miRNAs, and 699 mRNAs were differentially expressed in the plasma exosomes of patients with LUAD compared with healthy controls. Among them, 881 lncRNAs were upregulated and 135 were downregulated, 916 circRNAs were upregulated while 480 were downregulated, 45 miRNAs were upregulated while none were downregulated, and 591 mRNAs were upregulated while 108 were downregulated (p ≤ 0.05, and fold change ≥ 2). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed the biological functions of differentially expressed RNAs. Meanwhile, the RNA networks displayed the regulatory relationship between dysregulated RNAs. Finally, RT-qPCR validated that the expression of circ-0033861, circ-0043273, and circ-0011959 was upregulated in the plasma exosome of patients with LUAD compared to healthy controls (p = 0.0327, p = 0.0002, p = 0.0437, respectively).
This study proposed a newly discovered ncRNA–miRNA–mRNA/circRNA–miRNA–mRNA ceRNA network and identified that the expression of circulating circ-0033861, circ-0043273, and circ-0011959 was up-regulated in the plasma exosomes of patients with LUAD, offering valuable insights for exploring the potential function of exosomal noncoding RNA and identifying potential biomarkers for LUAD.
The role of solute carrier family 35 member F3 (SLC35F3) in lung adenocarcinoma (LUAD) remains unclear. To address this gap, we conducted a study employing bioinformatics analysis and experimental validation.
This study aimed to examine the expression patterns of SLC35F3 in various cancer types, particularly focusing on LUAD, by analyzing data from the Cancer Genome Atlas (TCGA) database to evaluate its clinical relevance. The research also explored potential regulatory mechanisms of SLC35F3, including its interactions with immune infiltration, tumor mutational burden (TMB), and drug sensitivity in LUAD. The investigation included analyzing SLC35F3 expression in single-cell sequencing of LUAD cells, examining genetic variations of SLC35F3 in LUAD, and assessing SLC35F3 expression in cell lines using quantitative real-time PCR (qRT-PCR).
The aberrant expression of SLC35F3 was observed in both pan-cancer and LUAD. In LUAD patients, a statistically significant increase in SLC35F3 expression was correlated with gender (p < 0.001) and was associated with poorer overall survival (OS) (p = 0.020). The expression of SLC35F3 was identified as an independent prognostic determinant in patients with LUAD (p = 0.032). SLC35F3 exhibited associations with various pathways, including cell cycle and more. SLC35F3 expression demonstrated correlations with immune infiltration, TMB, and some drugs in LUAD. Results indicated significant upregulation of SLC35F3 in both LUAD tissues and cell lines.
SLC35F3 may serve as a prognostic biomarker and immunotherapeutic target for patients with LUAD.
Not applicable.
As a common malignancy, lung cancer has a relatively poor prognosis and a low survival rate. In recent years, ferroptosis, as an emerging filed, has great promise in the potential treatment of cancer. Brucea javanica oil (BJO) is often used to treat various cancers. Oleic acid (OA) is the main ingredient of BJO. In this study, we investigated the role and molecular mechanism of OA in lung cancer treatment by promoting ferroptosis.
In this study, A549 cells and H1299 cells were used for in vitro experiments, and a CCK-8 test, scratch test, and MTT experiment were carried out. We examined reactive oxygen species (ROS), the JC-1 probe, glutathione (GSH) expression, lipid peroxidation, SDC4 mRNA levels, and ACSL4, SLC7A11, GPX4, and SDC4 protein levels.
The results showed that OA could inhibit the proliferation and migration of A549 cells and H1299 cells, SDC4 was a potential therapeutic target of OA against lung cancer, and OA treatment significantly inhibited the expression of SDC4 in A549 cells and H1299 cells. OA induces ferroptosis in A549 cells and H1299 cells, decreases GSH levels, increases lipid peroxidation levels, and decreases SDC4 mRNA expression; in addition, OA upregulates ACSL4 expression and decreases SLC7A11, GPX4, and SDC4 expression.
This study confirmed that OA could inhibit SDC4 expression and promote the occurrence of ferroptosis in A549 cells and H1299 cells through the GPX4/ACSL4 pathway, providing an effective basis for the use of drugs targeting ferroptosis in lung cancer treatment.
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