Advances in systemic immune inflammatory indices in non-small cell lung cancer: A review.

Lung cancer is one of the most prevalent cancers globally, with non-small cell lung cancers constituting the majority. These cancers have a high incidence and mortality rate. In recent years, a growing body of research has demonstrated the intricate link between inflammation and cancer, highlighting that inflammation and cancer are inextricably linked and that inflammation plays a pivotal role in cancer development, progression, and prognosis of cancer. The Systemic Immunoinflammatory Index (SII), comprising neutrophil, lymphocyte, and platelet counts, is a more comprehensive indicator of the host's systemic inflammation and immune status than a single inflammatory index. It is widely used in clinical practice due to its cost-effectiveness, simplicity, noninvasiveness, and ease of acquisition. This paper reviews the impact of SII on the development, progression, and prognosis of non-small cell lung cancer.

Research trends in cardiovascular tissue engineering from 1992 to 2022: a bibliometric analysis.

Background: Cardiovascular tissue engineering (CTE) is a promising technique to treat incurable cardiovascular diseases, such as myocardial infarction and ischemic cardiomyopathy. Plenty of studies related to CTE have been published in the last 30 years. However, an analysis of the research status, trends, and potential directions in this field is still lacking. The present study applies a bibliometric analysis to reveal CTE research trends and potential directions. Methods: On 5 August 2022, research articles and review papers on CTE were searched from the Web of Science Core Collection with inclusion and exclusion criteria. Publication trends, research directions, and visual maps in this field were obtained using Excel (Microsoft 2009), VOSviewer, and Citespace software. Results: A total of 2,273 documents from 1992 to 2022 were included in the final analysis. Publications on CTE showed an upward trend from 1992 [number of publications (Np):1] to 2021 (Np:165). The United States (Np: 916, number of citations: 152,377, H-index: 124) contributed the most publications and citations in this field. Research on CTE has a wide distribution of disciplines, led by engineering (Np: 788, number of citations: 40,563, H-index: 105). "Functional maturation" [red cluster, average published year (APY): 2018.63, 30 times], "cell-derived cardiomyocytes" (red cluster, APY: 2018.43, 46 times), "composite scaffolds" (green cluster, APY: 2018.54, 41 times), and "maturation" (red cluster, APY: 2018.17, 84 times) are the main emerging keywords in this area. Conclusion: Research on CTE is a hot research topic. The United States is a dominant player in CTE research. Interdisciplinary collaboration has played a critical role in the progress of CTE. Studies on functional maturation and the development of novel biologically relevant materials and related applications will be the potential research directions in this field.

TAK-242 protects against oxygen-glucose deprivation and reoxygenation-induced injury in brain microvascular endothelial cells and alters the expression pattern of lncRNAs.

Background: Deep hypothermic circulatory arrest (DHCA) is a technique used during the surgical treatment of aneurysms of the thoracic aorta in adult patients, and complex congenital heart disease in neonates. And brain microvascular endothelial cells (BMECs) are essential components of the cerebrovascular network and participate in maintaining the blood-brain barrier (BBB) and brain function. In our previous study, we found that oxygen-glucose deprivation and reoxygenation (OGD/R) activated Toll-like receptor 4 (TLR4) signaling in BMECs, and induced pyroptosis and inflammation. In this study, we further investigated the potential mechanism of ethyl(6R)-6-[N-(2-Chloro-4-fluorophenyl) sulfamoyl] cyclohex-1-ene-1-carboxylate (TAK-242) on BMECs under OGD/R, as in patients with sepsis, the TAK-242 was tested in clinical trials. Methods: To confirm the function of TAK-242 on BMECs under OGD/R, cell viability, inflammatory factors, inflammation-associated pyroptosis, and nuclear factor-κB (NF-κB) signaling were determined using Cell Counting Kit-8 (CCK-8) assay, enzyme-linked immunosorbent assay (ELISA), and western blotting, respectively. To investigate the lncRNAs associated with TLR4 during OGD/R, long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) expression patterns were profiled with RNA deep sequencing. Moreover, to confirm whether lncRNA-encoded short peptides, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used. Results: Relative control group, OGD/R inhibited the cell viability, increased the section of inflammatory factors secretion, including IL-1ß, IL-6, and TNF-α, and promoted the pathways of TLR4/NLRP3/Caspase-1 and TLR4/NF-κB. However, TAK-242 + OGD/R group promoted OGD/R cell viability, decreased OGD/R-induced inflammatory factors secretion, and inhibited the pathways of TLR4/NLRP3/Caspase-1 and TLR4/NF-κB. In addition, AABR07000411.1, AABR070006957.1, and AABR070008256.1 were decreased in OGD/R cells compared with controls, but TAK-242 restored their expression under OGD/R condition. AABR07000473.1, AC130862.4, and LOC10254972.6 were induced by OGD/R, but were suppressed in TAK-242 + OGD/R cells compared with OGD/R. Moreover, AABR07049961.1, AC127076.2, AABR07066020.1, and AABR07025303.1-encoded short peptides were dysregulated in OGD/R cells, and TAK-242 attenuated the dysregulation of AABR07049961.1, AC127076.2, and AABR07066020.1-encoded short peptides. Conclusions: TAK-242 alters the expression pattern of lncRNAs in OGD/R cells, and differently expressed lncRNAs may exert a protective effect against OGD/R injury through a mechanism of competing endogenous RNA (ceRNA) and encoding short peptides. These findings maybe provide a new theory basis for the treatment of DHCA.

Role of exosomes in non-small cell lung cancer and EGFR-mutated lung cancer.

As an important mediator of information transfer between cells, exosomes play a unique role in regulating tumor growth, supporting vascular proliferation, tumor invasion, and metastasis. Exosomes are widely present in various body fluids, and therefore they can be used as a potential tool for non-invasive liquid biopsy. The present study reviews the role of exosomes in liquid biopsy, tumor microenvironment formation, and epithelial-mesenchymal transition in non-small cell lung cancer (NSCLC). By targeting epidermal growth factor receptor (EGFR) therapy as a first-line treatment for patients with NSCLC, this study also briefly describes the occurrence of EGRF+ exosomes and the role of exosomes and their contents in non-invasive detection and potential therapeutic targets in EGFR-mutated lung cancer.

Role of exosomal noncoding RNA in esophageal carcinoma.

Esophageal cancer is a common malignant tumor with a high degree of malignancy. Understanding its pathogenesis and identifying early diagnostic biomarkers can significantly improve the prognosis of esophageal cancer patients. Exosomes are small double-membrane vesicles found in various body fluids containing various components (DNA, RNA, and proteins) that mediate intercellular signal communication. Non-coding RNAs are a class of gene transcription products that encode polypeptide functions and are widely detected in exosomes. There is growing evidence that exosomal non-coding RNAs are involved in cancer growth, metastasis and angiogenesis, and can also be used as diagnostic and prognostic markers. This article reviews the recent progress in exosomal non-coding RNAs in esophageal cancer, including research progress, diagnostic value, proliferation, migration, invasion, and drug resistance, provide new ideas for the precise treatment of esophageal cancer.

Rapid identification of high and low cadmium (Cd) accumulating rice cultivars using machine learning models with molecular markers and soil Cd levels as input data.

Excessive accumulation of cadmium (Cd) in rice grains threatens food safety and human health. Growing low Cd accumulating rice cultivars is an effective approach to produce low-Cd rice. However, field screening of low-Cd rice cultivars is laborious, time-consuming, and subjected to the influence of environment × genotype interactions. In the present study, we investigated whether machine learning-based methods incorporating genotype and soil Cd concentration can identify high and low-Cd accumulating rice cultivars. One hundred and sixty-seven locally adapted high-yielding rice cultivars were grown in three fields with different soil Cd levels and genotyped using four molecular markers related to grain Cd accumulation. We identified sixteen cultivars as stable low-Cd accumulators with grain Cd concentrations below the 0.2 mg kg-1 food safety limit in all three paddy fields. In addition, we developed eight machine learning-based models to predict low- and high-Cd accumulating rice cultivars with genotypes and soil Cd levels as input data. The optimized model classifies low- or high-Cd cultivars (i.e., the grain Cd concentration below or above 0.2 mg kg-1) with an overall accuracy of 76%. These results indicate that machine learning-based classification models constructed with molecular markers and soil Cd levels can quickly and accurately identify the high- and low-Cd accumulating rice cultivars.

CircFBXW7 Inhibits Proliferation, Migration, and Invasion of Nonsmall Cell Lung Cancer Cells by Regulating miR-492.

Background: CircFBXW7 has been determined to be involved in various cancers; however, its role in nonsmall cell lung cancer (NSCLC) remains unclear. This study examined the function and potential mechanism of circFBXW7 in NSCLC. Methods: The structure of circFBXW7 was verified via RT-PCR and Sanger sequencing. The expression of circFBXW7 in NSCLC was determined by qRT-PCR. The effect of circFBXW7 overexpression on the proliferation, migration, and invasion of NSCLC cells was examined by CCK-8 and Transwell assays. Furthermore, a circFBXW7-miRNA network was established to explore their interaction. Predicted miRNA was determined by qRT-PCR. Moreover, the miRNA mimics were synthesized, wherein its effect on proliferation, migration, and invasion of NSCLC cells overexpressed circFBXW7 was assessed. Results: The circularity of circFBXW7 was verified. The expression of circFBXW7 was found to be downregulated in NSCLC cells compared with that in normal human lung epithelial BEAS-2B cells. Overexpression of circFBXW7 reduced cell proliferation, migration, and invasion. Furthermore, according to the circFBXW7-miRNA network prediction and qRT-PCR validation, miR-492 was identified to be the target of circFBXW7. The inhibitory effect of circFBXW7 overexpression on cell proliferation, migration, and invasion was reversed by miR-492 mimics. Conclusion: CircFBXW7 is downregulated in NSCLC. CircFBXW7 inhibits NSCLC cells proliferation, migration, and invasion by regulating miR-492.

Soil amendments with ZnSO4 or MnSO4 are effective at reducing Cd accumulation in rice grain: An application of the voltaic cell principle.

Cadmium (Cd) contamination in paddy soil often results in elevated Cd concentrations in rice grain, which is a serious concern threatening food safety. Most of the Cd accumulated in rice grain is derived from its remobilization in paddy soil during the grain filling period when paddy water is drained. We have previously shown that the voltaic cell effect controls the oxidative release of cadmium sulfide (CdS) during the drainage period. Metal sulfides with lower electrochemical potentials than CdS can suppress the oxidation of CdS. In the present study, we tested whether amendments of ZnSO4 or MnSO4 could enhance the suppressive voltaic effect on Cd release and subsequent accumulation in rice grain. The one-time addition of ZnSO4 (75 kg/ha Zn) decreased CaCl2-extractable Cd concentrations in soils by 32-64% in pot experiments and by 16-30% in field trials during the drainage period. Consequently, Cd concentrations in brown rice were reduced by 74-87% and 60-72% in pot experiments and field trials, respectively. Importantly, this effect persisted in the second year without further addition. The amendment of MnSO4 had similar effects in decreasing soil extractable Cd and Cd concentrations in brown rice. These effects were not attributed to the addition of sulfate. A single application of such doses of ZnSO4 or MnSO4 (e.g. 75-150 kg/ha Zn or Mn) only caused a marginal increase in soil Zn or Mn concentrations and had no significant impact on grain yield. Taken together, amendments of ZnSO4 and/or MnSO4 (at the rate of 75-150 kg/ha Zn and or Mn) formed a protective voltaic cell partner against the oxidative dissolution of CdS and thus were highly effective in reducing Cd accumulation in rice grain. This work provides a simple but effective method to decrease soil Cd availability during soil drainage and mitigate Cd accumulation in rice to ensure food safety.

miR-666-3p Mediates the Protective Effects of Mesenchymal Stem Cell-derived Exosomes Against Oxygen-glucose Deprivation and Reoxygenation- induced Cell Injury in Brain Microvascular Endothelial Cells via Mitogen-activated Protein Kinase Pathway.

BACKGROUND: Previous studies have reported that mesenchymal stem cell (MSC)- derived exosomes can protect primary rat brain microvascular endothelial cells (BMECs) against oxygen-glucose deprivation and reoxygenation (OGD/R)-induced injury. OBJECTIVE: The aim was to identify the key factors mediating the protective effects of MSC-derived exosomes. METHODS: Primary rat BMECs were either pretreated or not pretreated with MSC-derived exosomes before exposure to OGD/R. Naïve cells were used as a control. After performing small RNA deep sequencing, quantitative reverse transcription polymerase chain reaction was performed to validate microRNA (miRNA) expression. The effects of rno-miR-666-3p on cell viability, apoptosis, and inflammation in OGD/R-exposed cells were assessed by performing the Cell Counting Kit 8 assay, flow cytometry, and enzyme-linked immunosorbent assay, respectively. Moreover, the role of rno-miR-666-3p in regulating gene expression in OGD/R-exposed cells was studied using mRNA deep sequencing. Lastly, to evaluate whether mitogen-activated protein kinase 1 (MAPK1) was the target of rno-miR-666-3p, western blotting and the dual-luciferase assay were performed. RESULTS: MSC-derived exosomes altered the miRNA expression patterns in OGD/R-exposed BMECs. In particular, the expression levels of rno-miR-666-3p, rno-miR-92a-2-5p, and rnomiR- 219a-2-3p decreased in OGD/R-exposed cells compared with those in the control; however, MSC-derived exosomes restored the expression levels of these miRNAs under OGD/R conditions. rno-miR-666-3p overexpression enhanced cell viability and alleviated the apoptosis of OGD/R-exposed cells. Moreover, rno-miR-666-3p suppressed OGD/R-induced inflammation. mRNA deep sequencing revealed that rno-miR-666-3p is closely associated with the MAPK signaling pathway. Western blotting and the dual-luciferase assay confirmed that MAPK1 is the target of rnomiR- 666-3p. CONCLUSION: MSC-derived exosomes restore rno-miR-666-3p expression in OGD/R-exposed BMECs. Moreover, this specific miRNA exerts protective effects against OGD/R by suppressing the MAPK signaling pathway.

Peripheral blood inflammation indices are effective predictors of anastomotic leakage in elective esophageal surgery.

BACKGROUND: This study investigated the predictive value of peripheral inflammatory indices, including neutrophil count, lymphocyte count, platelet count, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), in anastomotic leakage during elective esophageal surgery. METHODS: This retrospective study included all patients who underwent esophagectomy for esophageal squamous cell carcinoma from 2016 to 2020 in our institution. The peripheral blood inflammatory indices were obtained on preoperative days 1-7 (PRD 1-7), and postoperative days 1-3 (POD 1-3) and 4-7 (POD 4-7). Univariate, multivariate logistic, and receiver operating characteristic curve analyses were conducted to evaluate the diagnostic value of these peripheral blood inflammatory indices. RESULTS: A total of 198 patients were included in the study, and 25 (13%) patients experienced anastomotic leakage. Multivariate analyses identified diet, neutrophil count, and PLR on POD 1-3, and NLR on POD 4-7 as independent factors associated with anastomotic leakage. Using the receiver operating characteristic curve, the variable with the best area under curve was a neutrophil cutoff count of 4.1 [0.737; 95% CI: 0.639-0.835], with a sensitivity and specificity of 60.0% and 66.5%, respectively. This was followed by an NLR cutoff value of 9.5 on POD 4-7 (0.628; 95% CI: 0.505-0.752) and a cutoff PLR value of 220.1 on POD 1-3 (0.643; 95% CI: 0.536-0.750). Diet showed a poor result on the receiver operating characteristic curve analysis. CONCLUSIONS: Neutrophil count and PLR on POD 1-3 and NLR on POD 4-7 were shown to have predictive value for anastomotic leakage in elective esophageal surgery.

Mesenchymal Stem Cell-derived Exosomes Rescue Oxygen-Glucose Deprivation-induced Injury in Endothelial Cells.

OBJECTIVE: The effects of mesenchymal stem cell (MSC)-derived exosomes on brain microvascular endothelial cells under oxygen-glucose deprivation (OGD), which mimic cells in deep hypothermic circulatory arrest (DHCA) in vitro, are yet to be studied. METHODS: MSCs were co-cultured with primary rat brain endothelial cells, which were then exposed to OGD. Cell viability, apoptosis, the inflammatory factors (IL-1ß, IL-6, and TNF-α), and the activation of inflammation-associated TLR4-mediated pyroptosis and the NF-κB signaling pathway were determined. Furthermore, exosomes derived from MSCs were isolated and incubated with endothelial cells to investigate whether the effect of MSCs is associated with MSCderived exosomes. Apoptosis, cell viability, and the inflammatory response were also analyzed in OGD-induced endothelial cells incubated with MSC-derived exosomes. RESULTS: OGD treatment promoted endothelial cell apoptosis, induced the release of inflammatory factors IL-1ß, IL-6, and TNF-α, and inhibited cell viability. Western blot analysis showed that OGD treatment-induced TLR4, and NF-κB p65 subunit phosphorylation and caspase-1 upregulation, while co-culture with MSCs could reduce the effect of OGD treatment on endothelial cells. As expected, the effect of MSC-derived exosomes on OGD-treated endothelial cells was similar to that of MSCs. MSC-derived exosomes alleviated the OGD-induced decrease in the viability of endothelial cells, and increased levels of apoptosis, inflammatory factors, and the activation of inflammatory and inflammatory focal pathways. CONCLUSION: Both MSCs and MSC-derived exosomes attenuated OGD-induced rat primary brain endothelial cell injury. These findings suggest that MSC-derived exosomes mediate at least some of the protective effects of MSCs on endothelial cells.

Retrograde Cerebral Perfusion Results in Better Perfusion to the Striatum Than the Cerebral Cortex During Deep Hypothermic Circulatory Arrest: A Microdialysis Study.

It remains controversial whether contemporary cerebral perfusion techniques, utilized during deep hypothermic circulatory arrest (DHCA), establish adequate perfusion to deep structures in the brain. This study aimed to investigate whether selective antegrade cerebral perfusion (SACP) or retrograde cerebral perfusion (RCP) can provide perfusion equally to various anatomical positions in the brain using metabolic evidence obtained from microdialysis. Eighteen piglets were randomly assigned to 40 min of circulatory arrest (CA) at 18°C without cerebral perfusion (DHCA group, n = 6) or with SACP (SACP group, n = 6) or RCP (RCP group, n = 6). Microdialysis parameters (glucose, lactate, pyruvate, and glutamate) were measured every 30 min in cortex and striatum. After 3 h of reperfusion, brain tissue was harvested for Western blot measurement of α-spectrin. After 40 min of CA, the DHCA group showed marked elevations of lactate and glycerol and a reduction in glucose in the microdialysis perfusate (all P < 0.05). The changes in glucose, lactate, and glycerol in the perfusate and α-spectrin expression in brain tissue were similar between cortex and striatum in the SACP group (all P > 0.05). In the RCP group, the cortex exhibited lower glucose, higher lactate, and higher glycerol in the perfusate and higher α-spectrin expression in brain tissue compared with the striatum (all P < 0.05). Glutamate showed no difference between cortex and striatum in all groups (all P > 0.05). In summary, SACP provided uniform and continuous cerebral perfusion to most anatomical sites in the brain, whereas RCP resulted in less sufficient perfusion to the cortex but better perfusion to the striatum.

Selective antegrade cerebral perfusion attenuating the TLR4/NF-κB pathway during deep hypothermia circulatory arrest in a pig model.

OBJECTIVES: The alteration of the Toll-like receptor/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway during deep hypothermia circulatory arrest (DHCA) has not yet been defined. The aim of this study was to explore the expression of the TLR4/NF-κB pathway cytokine in cerebral injury resulting from DHCA as well as the effect of selective antegrade cerebral perfusion (SACP) on TLR4/NF-κB pathway expression. METHODS: Twelve pigs were randomly assigned to DHCA alone (n = 6) or DHCA with SACP (n = 6) at 18°C for 80 min. Serum interleukin (IL)-6 was assayed by ELISA. Apoptosis and NF-κB proteins were detected by fluorescence TUNEL and Western blot, respectively. The level of TLR4 mRNA and protein were determined through qRT-PCR and Western blot. RESULTS: The serum IL-6 level of the SACP group was significantly lower than that of the DHCA group at the end of circulation arrest and experimentation. Apoptotic index and NF-κB protein were apparently lower in SACP animals (p < 0.05). Compared to the DHCA group, the levels of TLR4 protein and mRNA in the SACP group were lower with significance (p < 0.05). CONCLUSIONS: The TLR4/NF-κB signaling pathway plays a critical role in the pathogenesis of DHCA cerebral injury. Attenuation of the TLR4/NF-κB inflammatory cytokines probably contributes to the neuroprotective effect of SACP. The TLR4/NF-κB inflammatory signaling pathway may be a novel therapeutic target for developing a new strategy for neuroprotection in DHCA.

Is selective antegrade cerebral perfusion superior to retrograde cerebral perfusion for brain protection during deep hypothermic circulatory arrest? Metabolic evidence from microdialysis.

OBJECTIVES: This study aimed to investigate whether selective antegrade cerebral perfusion or retrograde cerebral perfusion is a better technique for brain protection in deep hypothermic circulatory arrest by obtaining metabolic evidence from microdialysis. DESIGN: Randomized, animal study. SETTING: Assisted circulation laboratory. SUBJECTS: Eighteen piglets of either sex (9.8 ± 3.1 kg). INTERVENTIONS: Animals were randomly assigned to 40 minutes of circulatory arrest at 18°C without cerebral perfusion (deep hypothermic circulatory arrest group, n = 6) or with selective antegrade cerebral perfusion (selective antegrade cerebral perfusion group, n = 6) or retrograde cerebral perfusion (retrograde cerebral perfusion group, n = 6). Reperfusion was continued for 3 hours. MEASUREMENTS AND MAIN RESULTS: Microdialysis (glucose, lactate, pyruvate, and glycerol) variables in the cortex dialysate were measured every 30 minutes. Intracerebral pressure and serum S-100 levels were also monitored. After 3 hours of reperfusion, cortical tissue was harvested for terminal deoxynucleotidyl transferase dUTP nick-end labeling staining. After 40 minutes of circulatory arrest, the deep hypothermic circulatory arrest group presented marked elevations of intracerebral pressure, and serum S-100 levels were higher in the deep hypothermic circulatory arrest group than in the other two groups (p < 0.001, respectively). The selective antegrade cerebral perfusion group exhibited higher glucose, lower lactate, and lower glycerol levels and a lower lactate-to-pyruvate ratio in comparison to the deep hypothermic circulatory arrest group (p < 0.05, respectively); the retrograde cerebral perfusion group had lower lactate and glycerol levels and a lower lactate-to-pyruvate ratio (p < 0.05, respectively) but similar glucose levels compared to deep hypothermic circulatory arrest alone. Furthermore, selective antegrade cerebral perfusion provided better preservation of energy and cell integrity than retrograde cerebral perfusion with higher glucose and lower glycerol levels (p < 0.05, respectively). After 3 hours of reperfusion, fewer apoptotic neurons were found in selective antegrade cerebral perfusion animals than in the other two groups (p < 0.05, respectively). CONCLUSIONS: Both selective antegrade cerebral perfusion and retrograde cerebral perfusion were superior to deep hypothermic circulatory arrest alone during circulatory arrest. Retrograde cerebral perfusion was a moderate technique that had similar advantages with regard to less cerebral edema, better clearance of metabolic waste, and lower levels of biomarkers of injury than selective antegrade cerebral perfusion, but its capacity for energy preservation, maintenance of cellular integrity, and protection against apoptosis was lower than that of selective antegrade cerebral perfusion.