The expression characteristic and prognostic role of Siglec-15 in lung adenocarcinoma.

Sialic acid-binding immunoglobulin-like lectin-15 (Siglec-15) has been identified as an immune suppressor and a promising candidate for immunotherapy of cancer management. However, the association between Siglec-15 expression and clinicopathological features of lung adenocarcinoma (LUAD), especially the prognostic role, is not fully elucidated. In this present study, a serial of bioinformatics analyses in both tissue and cell levels were conducted to provide an overview of Siglec-15 expression. Real-time quantitative PCR (qPCR) test, western blotting assay, and immunohistochemistry (IHC) analyses were conducted to evaluate the expression of Siglec-15 in LUAD. Survival analysis and Kaplan-Meier curve were employed to describe the prognostic parameters of LUAD. The results of bioinformatics analyses demonstrated the up-regulation of Siglec-15 expression in LUAD. The data of qPCR, western blotting, and IHC analyses further proved that the expression of Siglec-15 in LUAD tissues was significantly increased than that in noncancerous tissues. Moreover, the expression level of Siglec-15 protein in LUAD was substantially associated with TNM stage. LUAD cases with up-regulated Siglec-15 expression, positive N status, and advance TNM stage suffered a critical unfavorable prognosis. In conclusion, Siglec-15 could be identified as a novel prognostic biomarker in LUAD and targeting Siglec-15 may provide a promising strategy for LUAD immunotherapy.

Prognostic Role of Pretreatment Prognostic Nutritional Index in Advanced Lung Cancer Patients Receiving First-Line Immunotherapy: A Meta-Analysis.

The aim of this study was to further explore the association between pretreatment prognostic nutritional index (PNI) and survival among advanced lung cancer patients who received the first-line immunotherapy based on current relevant studies. Several databases were searched up to July 17, 2023. Progression-free survival (PFS) and overall survival (OS) were primary outcomes and the hazard ratios (HRs) with 95% confidence intervals (CIs) were combined. Subgroup analysis based on the pathological type [non-small cell lung cancer (NSCLC) vs small cell lung cancer (SCLC)] and combination of other therapies (yes vs no) were performed. Ten studies with 1291 patients were included eventually. The pooled results demonstrated that higher pretreatment PNI was significantly related to improved PFS (HR=0.62, 95% CI: 0.48-0.80, P＜0.001) and OS (HR=0.52, 95% CI: 0.37-0.73, P＜0.001). Subgroup analysis revealed that the predictive role of pretreatment PNI for PFS (HR=0.61, 95% CI: 0.45-0.81, P=0.001) and OS (HR=0.52, 95% CI: 0.35-0.77, P=0.001) was only observed among NSCLC patients and the combination of other therapies did not cause an impact on the prognostic role of PNI in lung cancer. Pretreatment PNI was significantly associated with prognosis in advanced NSCLC receiving first-line immunotherapy and patients with a lower pretreatment PNI had poorer survival.

HDAC3 Inhibitor RGFP966 Ameliorated Neuroinflammation in the Cuprizone-Induced Demyelinating Mouse Model and LPS-Stimulated BV2 Cells by Downregulating the P2X7R/STAT3/NF-κB65/NLRP3 Activation.

Suppression of excessive microglial overactivation can prevent the progression of multiple sclerosis (MS). Histone deacetylases 3 inhibitor (HDAC3i) has been demonstrated to exert anti-inflammatory effects by suppressing microglia (M1-liked) activation. Here, we demonstrate that the RGFP966 (a selective inhibitor of HDAC3) protects white matter after cuprizone-induced demyelination, as shown by reductions in neurological behavioral deficits and increases in myelin basic protein. Moreover, in this study, we found that RGFP966 caused a significant reduction in the levels of inflammatory cytokines, including IL-1ß, TNF-α, as well as iNOS, and inhibited microglial (M1-liked) activation in the experimental cuprizone model and LPS-stimulated BV2 cells. Meanwhile, RGFP966 alleviated apoptosis of LPS-induced BV2 cells in vitro. Furthermore, RGFP966 suppressed the expression of P2X7R, NLRP3, ASC, IL-18, IL-1ß, and caspase-1, inhibited the ratio of phosphorylated-STAT3/STAT3 and phosphorylated NF-κB p65/NF-κB p65, as well as increased acetylated NF-κB p65 in vitro and in vivo. Furthermore, we confirmed that brilliant blue G (antagonists of P2X7R) suppressed the expression of microglial NLRP3, IL-18, IL-1ß, caspase-1, NF-κB p65 (including phosphorylated NF-κB p65), and STAT3 (including phosphorylated STAT3) in vitro. These findings demonstrated that RFFP966 alleviated the inflammatory response and exerted a neuroprotective effect possibly by modulating P2X7R/STAT3/NF-κB65/NLRP3 signaling pathways. Thus, HDAD3 might be considered a promising intervention target for neurodegenerative diseases, such as MS.

Preparation, Characterization, Evaluation of Neuroprotective Effect, and Related Mechanisms of Phosphatidylserine Emulsion in 5- and 12-Week Old Mice.

Phosphatidylserine (PS) improves learning and memory capacity. In this study, PS formulation was optimized by a response surface methodology. Moreover, we found that PS not only functions as a biologically active component in food preparations but also improves the emulsion's physical stability. Our results showed that the PS emulsions are characterized by a smaller particle size, higher ζ-potential (negative), higher viscosity, and lower surface tension and centrifugal stability constants than the emulsion without PS. Furthermore, we explored the neuroprotective effects of PS emulsion and its underlying mechanisms. Treatment with 2% (w/w) PS emulsion for three months enhanced spatial learning and memory in 5- and 12-week old mice in the Morris water maze test. Western-blotting analysis displayed that the 2% (w/w) PS emulsion treated group upregulated BDNF, TrkB, PSD95, mTOR, MBP, and ErbB4 expression in the hippocampus of 5- and 12-week old mice. Reverse transcription polymerase chain reaction (RT-PCR) analysis revealed elevated Nrg-1 and ErbB4 mRNA expression in the 2% (w/w) PS emulsion treated groups, and high Nrg-1 and ErbB4 expression levels were associated with better myelination. In conclusion, we reported PS emulsions with high stability and high bioavailability. Meanwhile, 2% (w/w) PS emulsion enhances learning, memory, and myelination in mice by activating the BDNF/TrkB and Nrg-1/ErbB4 signaling.

Expression and Clinical Significance of lncRNA OSER1-AS1 in Peripheral Blood of Patients with Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) is a malignant cancer worldwide. Long non-coding RNAs (lncRNAs) have emerged as key players in the development and progression of NSCLC, and may be potential biomarkers of NSCLC. Here, we investigated the clinical significance of lncRNA oxidative stress responsive serine rich 1 antisense RNA 1 (OSER1-AS1) in peripheral blood of patients with NSCLC. OSER1-AS1 in peripheral blood of patients with lung squamous cell carcinoma (LUSC), lung adenocarcinoma (LUAD), and healthy subjects was detected, and the clinical diagnostic efficacy was analyzed. The correlation between OSER1-AS1 expression and clinicopathological features in patients with LUSC and LUAD was analyzed. The downstream mechanism of OSER1-AS1 was explored. The area under the ROC curve of lncRNA OSER1-AS1 and miR-1298-5p/CHSY3 in LUSC and LUAD was compared using the MedCalc analysis. OSER1-AS1 was low in peripheral blood of patients with LUSC and LUAD. The area under the ROC curve for predicting LUSC was 0.800. The area under the ROC curve for predicting LUAD was 0.728. In LUSC and LUAD, OSER1-AS1 deficiency was associated with tumor node metastasis stage, lymph node metastasis, distal metastasis, and poor prognosis. miR-1298-5p was highly expressed, while chondroitin sulfate synthase 3 (CHSY3) was lowly expressed in patients with LUSC and LUAD. miR-1298-5p had target relations with OSER1-AS1 and CHSY3. lncRNA OSER1-AS1 had a higher diagnostic value in patients with NSCLC than miR-1298-5p and CHSY3. Overall, low expression of OSER1-AS1 in peripheral blood of NSCLC patients has high clinical significance, which provides a certain reference value for NSCLC early diagnosis.

Surgical procedure of segmentectomy as a possible cause of postoperative cerebral embolism: a case report.

BACKGROUND: Cerebral embolism after lobectomy is a life-threatening complication during the early postoperative period. However, it is unclear if cerebral embolism can develop after segmentectomy. CASE PRESENTATION: We experienced a case of a 37-year-old man who demonstrated early symptom of acute ischemic stroke in early postoperative period after right upper posterior segmentectomy and performed intra-arterial mechanical thrombectomy (IAMT) successfully. CONCLUSIONS: Long and irregular pulmonary vein stump (PVS) and endothelial injury caused by surgical procedure may lead to cerebral embolism after segmentectomy. We believe that doing preoperative pulmonary vascular assessment and using appropriate surgical procedure may reduce the rate of cerebral embolism.

Response of various conduit arteries in tachycardia- and volume overload-induced heart failure.

Although hemodynamics changes occur in heart failure (HF) and generally influence vascular function, it is not clear whether various HF models will affect the conduit vessels differentially or whether local hemodynamic forces or systemic factors are more important determinants of vascular response in HF. Here, we studied the hemodynamic changes in tachycardia or volume-overload HF swine model (created by either high rate pacing or distal abdominal aortic-vena cava fistula, respectively) on carotid, femoral, and renal arteries function and molecular expression. The ejection fraction was reduced by 50% or 30% in tachycardia or volume-overload model in four weeks, respectively. The LV end diastolic volume was increased from 65 ± 22 to 115 ± 78 ml in tachycardia and 67 ± 19 to 148 ± 68 ml in volume-overload model. Flow reversal was observed in diastolic phase in carotid artery of both models and femoral artery in volume-overload model. The endothelial function was also significantly impaired in carotid and renal arteries of tachycardia and volume-overload animals. The endothelial dysfunction was observed in femoral artery of volume-overload animals but not tachycardia animals. The adrenergic receptor-dependent contractility decreased in carotid and femoral arteries of tachycardia animals. The protein expressions of NADPH oxidase subunits increased in the three arteries and both animal models while expression of MnSOD decreased in carotid artery of tachycardia and volume-overload model. In conclusion, different HF models lead to variable arterial hemodynamic changes but similar vascular and molecular expression changes that reflect the role of both local hemodynamics as well as systemic changes in HF.

Increased aortic stiffness elevates pulse and mean pressure and compromises endothelial function in Wistar rats.

An increase in pulse pressure (PP) is highly associated with hypertension. The goal of this study was to determine the effect of increased aortic stiffness on PP and endothelial dysfunction as precursors to hypertension. A rat model of suddenly increased aortic stiffness by use of a nonconstrictive restraint (glue coating) on aortic surface was created to investigate the change of PP and mean arterial pressure (MAP). Group I (n = 16) underwent aorta restraint for 4 wk. Group II (n = 12) underwent aortic restraint for 4 wk, followed by restraint removal to evaluate extent of reversibility for additional 4 wk. The aortic and peripheral endothelial function was assessed by ACh-stimulated endothelium-dependent vasodilation. The level of nitrate/nitrite (NOx), endothelin-1 (ET-1), and prostacyclin (PGI2) were measured in the serum and artery tissue. We found that aortic stiffening causes a significant increase in PP and MAP (P < 0.05). The endothelial function was markedly blunted (P < 0.05) in both aorta and small peripheral artery. After removal of the restraint, the impaired endothelium function persisted in the aorta likely due to sustained deterioration of aortic wall, but was partially restored in peripheral artery. The endothelial dysfunction was correlated with a decrease in NOx and PGI2 (P < 0.05) and an increase in ET-1 (P < 0.05). Our results show that aortic stiffening results in widening of PP, which affected endothelium function through changes in synthesis of NOx, ET-1, and PGI2. These findings suggest that increased aortic stiffness may be a cause of increased PP and a precursor to hypertension.

Endothelial actin depolymerization mediates NADPH oxidase-superoxide production during flow reversal.

Slow moving blood flow and changes in flow direction, e.g., negative wall shear stress, can cause increased superoxide (O2(·-)) production in vascular endothelial cells. The mechanism by which shear stress increases O2(·-) production, however, is not well established. We tested the hypothesis that actin depolymerization, which occurs during flow reversal, mediates O2(·-) production in vascular endothelial cells via NADPH oxidase, and more specifically, the subunit p47(phox). Using a swine model, we created complete blood flow reversal in one carotid artery, while the contralateral vessel maintained forward blood flow as control. We measured actin depolymerization, NADPH oxidase activity, and reactive oxygen species (ROS) production in the presence of various inhibitors. Flow reversal was found to induce actin depolymerization and a 3.9 ± 1.0-fold increase in ROS production as compared with forward flow. NADPH oxidase activity was 1.4 ± 0.2 times higher in vessel segments subjected to reversed blood flow when measured by a direct enzyme assay. The NADPH oxidase subunits gp91(phox) (Nox2) and p47(phox) content in the vessels remained unchanged after 4 h of flow reversal. In contrast, p47(phox) phosphorylation was increased in vessels with reversed flow. The response caused by reversed flow was reduced by in vivo treatment with jasplakinolide, an actin stabilizer (only a 1.7 ± 0.3-fold increase). Apocynin (an antioxidant) prevented reversed flow-induced ROS production when the animals were treated in vivo. Cytochalasin D mimicked actin depolymerization in vitro and caused a 5.2 ± 3.0-fold increase in ROS production. These findings suggest that actin filaments play an important role in negative shear stress-induced ROS production by potentiating NADPH oxidase activity, and more specifically, the p47(phox) subunit in vascular endothelium.

[Chemical constituents from roots of Ferula sinkiangensis].

OBJECTIVE: To study the chemical constituents of the roots of Ferula sinkiangensis. METHOD: Compounds were isolated by repeated chromatography on silica gel. Their structures were elucidated by chemical and spectroscopic methods. RESULT: Seven compounds were identified as fekrynol (1), fekolone (2), farnesiferol B (3), isosamarcandin (4), episamarcandin (5), farnesiferol C (6), umbelliferone (7). CONCLUSION: All the compounds were obtained from this plant for the first time.

Sesquiterpene coumarins from the roots of Ferula sinkiangensis and Ferula teterrima.

Three new natural sesquiterpene coumarins, isofeterin (1), lehmannolol (3), sinkianone (4), and one known compound, lehmannolone (2), were isolated from the roots of Ferula teterrima and Ferula sinkiangensis. Their chemical structures were established on the basis of spectroscopic analysis, including X-ray crystallography and CD spectrum measurements for determining the absolute configuration of compound 2.

[Establishment of the control substance of plant drug and fingerprints of Coptis chinensis].

OBJECTIVE: To establish the control substance of plant drug (CSPD) of Coptis chinensis Franch. and its proton nuclear magnetic resonance (1H NMR) and high performance liquid chromatography (HPLC) fingerprints for the purpose of original identification. METHODS: The CSPD and their 1H NMR and HPLC fingerprints of Coptis chinensis were obtained by standardized procedure. Chemical components were isolated from the CSPD by silica gel column chromatography. By elucidation of their structures, the assignments of the characteristic signals in fingerprints could be achieved. RESULTS; The 1H NMR and HPLC fingerprints of the samples from various sources had wonderful reproducibility and characteristic features. Furthermore, five main compounds were isolated from CSPD and their structures were authenticated by spectral analysis as palmatine chloride, berberine chloride, epiberberine chloride, coptisine chloride, and jatrorrhizine chloride, respectively. The 1H NMR and HPLC fingerprints of the CSPD of Coptis chinensis showed mainly the characteristic signals of the berberine-type compounds isolated in this work. CONCLUSION: The 1H NMR and HPLC fingerprints of the CSPD of Coptis chinensis exhibit the structures and total composition of the main active constituents in it, and can be used for its original identification and quality evaluation.