Analysis of related factors of CRA in lung cancer patients with different serum iron levels: A retrospective cohort study.

BACKGROUND: Serum iron, an essential component of hemoglobin (Hb) synthesis in vivo, is a crucial parameter for evaluating the body's iron storage and metabolism capacity. Iron deficiency leads to reduced Hb synthesis in red blood cells and smaller red blood cell volume, ultimately resulting in iron-deficiency anemia. Although serum iron cannot independently evaluate iron storage or metabolism ability, it can reflect iron concentration in vivo and serve as a good predictor of iron-deficiency anemia. Therefore, exploring the influence of different serum iron levels on anemia and diagnosing and treating iron deficiency in the early stages is of great significance for patients with lung cancer. AIM: This study aims to explore the related factors of cancer-related anemia (CRA) in lung cancer and construct a nomogram prediction model to evaluate the risk of CRA in patients with different serum iron levels. METHODS: A single-center retrospective cohort study was conducted, including 1610 patients with lung cancer, of whom 1040 had CRA. The relationship between CRA and its influencing factors was analyzed using multiple linear regression models. Lung cancer patients were divided into two groups according to their serum iron levels: decreased serum iron and normal serum iron. Each group was randomly divided into a training cohort and a validation cohort at a ratio of 7:3. The influencing factors were screened by univariate and multivariate logistic regression analyses, and nomogram models were constructed. The area under the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the models. RESULTS: CRA in lung cancer is mainly related to surgery, chemotherapy, Karnofsky Performance Status (KPS) score, serum iron, C-reactive protein (CRP), albumin, and total cholesterol (p < 0.05). CRA in lung cancer patients with decreased serum iron is primarily associated with albumin, age, and cancer staging, while CRA in lung cancer patients with normal serum iron is mainly related to CRP, albumin, total cholesterol, and cancer staging. The area under the ROC curve of the training cohort and validation cohort for the prediction model of lung cancer patients with decreased serum iron was 0.758 and 0.760, respectively. Similarly, the area under the ROC curve of the training cohort and validation cohort for the prediction model of lung cancer patients with normal serum iron was 0.715 and 0.730, respectively. The calibration curves of both prediction models were around the ideal 45° line, suggesting good discrimination and calibration. DCA showed that the nomograms had good clinical utility. CONCLUSION: Both models have good reliability and validity and have significant clinical value. They can help doctors better assess the risk of developing CRA in lung cancer patients. CRP is a risk factor for CRA in lung cancer patients with normal serum iron but not in patients with decreased serum iron. Therefore, whether CRP and the inflammatory state represented by CRP will further aggravate the decrease in serum iron levels, thus contributing to anemia, warrants further study.

HIF­1α protects PC12 cells from OGD/R­induced cell injury by regulating autophagy flux through the miR­20a­5p/KIF5A axis.

Hypoxia inducible factor 1α (HIF­1α) has been reported to play a key role in protecting neurons from ischaemic injury. However, the exact molecular mechanisms remain largely unclear. PC12 cells were exposed to oxygen glucose deprivation/reoxygenation (OGD/R) conditions to mimic ischaemic injury in vitro. The expression of the HIF­1α mRNA, miR­20a­5p, and kinesin family member 5A (KIF5A) mRNA was tested using qRT-PCR. Levels of the HIF­1α, LC3I/II, P62, LAMP2, cathepsin B (CTSB) and KIF5A proteins were determined using western blotting. The CCK­8 assay was conducted to assess PC12 cell viability. DQ­Red­BSA and LysoSensor Green DND­189 dyes were employed to measure the proteolytic activity and pH of lysosomes, respectively. The interaction between miR­20a­5p and HIF­1α or KIF5A was verified by performing chromatin immunoprecipitation (ChIP) and/or dual­luciferase reporter assays. TUNEL staining was adopted to assess PC12 cell death. GFP­LC3 and RFP­GFP­LC3 probes were used to examine the autophagy status and autophagy flux of PC12 cells. A rat middle cerebral artery occlusion­reperfusion (MCAO/R) model was established to investigate the role of the HIF­1α/miR­20a­5p/KIF5A axis in ischaemic stroke in vivo. OGD/R exposure initiated PC12 cell autophagy and injury. HIF­1α expression was substantially increased in PC12 cells after OGD/R exposure. Overexpression of HIF­1α reversed the effects of OGD/R on reducing cell viability, blocking autophagy flux and inducing lysosome dysfunction. These rescue effects of HIF­1α depended on KIF5A. HIF­1α negatively regulated miR­20a­5p expression by targeting its promoter region, and miR­20a­5p directly targeted and negatively regulated the KIF5A mRNA. Overexpression of miR­20a­5p abolished the effects of HIF­1α on rescuing OGD/R­induced injury in PC12 cells. The effects of the HIF­1α/miR­20a­5p/KIF5A axis were verified in MCAO/R rats. HIF­1α protects PC12 cells from OGD/R­induced cell injury by regulating autophagy flux through the miR­20a­5p/KIF5A axis.

LncRNA nuclear-enriched abundant transcript 1 aggravates cerebral ischemia/reperfusion injury through activating early growth response-1/RNA binding motif protein 25 axis.

Ischemic stroke is a major global health issue. Ischemia and subsequent reperfusion results in stroke-related brain injury. Previous studies have demonstrated that nuclear-enriched abundant transcript 1 (NEATa and early growth response 1 (EGR1) are involved in ischemia reperfusion (IR) injury). In this study, we aimed to explore the roles of NEAT1/EGR1 axis as well as its downstream effector RNA binding motif protein 25 (RBM25) in cerebral IR injury. Oxygen-glucose deprivation/reperfusion (OGD/R) and middle cerebral artery occlusion (MCAO) were used to establish in vitro and in vivo models of cerebral IR injury, respectively. According to our data, NEAT1, EGR1, and RBM25 levels were elevated in OGD/R-exposed SK-N-SH and SH-SY5Y cells and cerebral cortex of MCAO mice. NEAT1, EGR1, or RBM25 knockdown effectively reduced infarct volumes and apoptosis, and improved neurological function. Mechanistically, NEAT1 directly interacted with EGR1, which restrained WW domain containing E3 ubiquitin protein ligase 1 (WWP1)-mediated ubiquitination of EGR1 and subsequently caused EGR1 accumulation. EGR1 bound to RBM25 promoter and transcriptionally activated RBM25. Rescue experiments indicated that RBM25 overexpression abolished the therapeutic effects of NEAT1 knockdown. In conclusion, this work identified a novel NEAT1/EGR1/RBM25 axis in potentiating brain injury after IR insults, suggesting a potential therapeutic target for ischemic stroke.

LncRNA RMRP accelerates autophagy-mediated neurons apoptosis through miR-3142/TRIB3 signaling axis in alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a major neurodegenerative disorder. The functions of lncRNA RMRP have been characterized mainly in various human cancers. However, the functional network of RMRP in AD progression remains unknown. METHODS: Human serum samples, AD transgenic (Tg) mice as well as SH-SY5Y cells were used in this study. The RNA expression patterns of RMRP, miR-3142 and TRIB3 were assessed by quantitative real-time PCR (qRT-PCR). Levels of apoptosis- or autophagy-associated biomarkers and TRIB3 level were evaluated using immunohistochemistry (IHC), western blotting or immunofluorescence assays, respectively. Bioinformatics methods and luciferase assays were used to predict and validate the interactions among RMRP, miR-3142, and TRIB3. Flow cytometry, TUNEL staining and EdU assays were used to examine the apoptosis and proliferation of neurons, respectively. RESULTS: The elevated RMRP and TRIB3 expressions and activation of autophagy were observed in AD. Knockdown of RMRP restrained neuronal apoptosis and autophagy activation in vitro and in vivo. Interestingly, TRIB3 overexpression reversed the biological effects of RMRP silencing on Aß1-42-induced cell apoptosis and autophagy. Further mechanistic analysis showed RMRP acted as a sponge of miR-3142 to elevate TRIB3 level. CONCLUSION: These data illustrated that knockdown of RMRP inhibited autophagy and apoptosis via regulating miR-3142/TRIB3 axis in AD, suggesting that inhibition of RMRP maybe a therapeutic strategy for AD.

[Blade acupuncture combined with functional exercise for chronic pain after non-small cell lung cancer surgery: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy of blade acupuncture combined with functional exercise for chronic pain after non-small cell lung cancer surgery. METHODS: A total of 62 patients with chronic pain after surgery for non-small cell lung cancer were randomly divided into an observation group and a control group, 31 cases in each group. The patients in the control group were treated with functional exercise. On the base of the treatment in the control group, the patients in the observation group were treated with blade acupuncture at the tendon nodes or painful points, once a week for 4 weeks. The visual analogue scale (VAS) scores of pain before treatment and day 1, day 7, day 14, day 28 of treatment and day 90, day 180 when follow up were compared between the two groups; the brief pain inventory (BPI) scores before and after treatment were compared between the two groups. RESULTS: The VAS score in the observation group at each time point after treatment was lower than that before treatment (P<0.01), and lower than that in the control group (P<0.01). Compared before treatment, the daily life score, emotion score, walking ability score, sleep score and life enjoyment score and total score of BPI in the observation group were reduced after treatment (P<0.05), and the daily life score, emotion score, sleep score and total score of BPI in the observation group were lower than those in the control group (P<0.05). CONCLUSION: The blade acupuncture combined with functional exercise could effectively alleviate the chronic pain after non-small cell lung cancer surgery, improve the quality of life of patients, and the effect is lasting and stable.

[Effects of arbuscular mycorrhizal fungi on metabolism of aroma substances in tobacco]. / ä¸›æžèŒæ ¹çœŸèŒå¯¹çƒŸè‰é¦™æ°”ç›¸å ³ç‰©è´¨ä»£è°¢çš„å½±å“.

Arbuscular mycorrhizal fungi (AMF) can promote nutrient absorption and improve stress resistance of host plants. The effects of AMF on aroma substance metabolism were rarely examined. In this study, we investigated the effects of AMF (Glomus mosseae) on glands and metabolism of aroma substances in tobacco leaves. The results showed that the density of gland hair and the relative expression of the glandular-specific lipid transporter gene NtLTP1, which was necessary to induce lipid secretion, were higher in the leaves of tobacco inoculated with AMF. The content of main aroma substances in tobacco leaves, such as carotenoids, chlorogenic acid and solanesol, were increased. Moreover, AMF inoculation increased the activities of phenylalanine ammonia-lyase (PAL) and polyphenol oxidase (PPO), the key aroma substance synthesis enzymes, and caused upregulation in the relative expression of phenylalanine transaminase, polyphenoloxidase, flavonoids alcoholase and squalene synthase encoding genes. In all, the symbiosis with G. mosseae could increase the abundance and secretory activity of glandular hairs and promote the synthesis of aroma substances in tobacco leaves.