Abstract This study leverages nanotechnology by encapsulating indocyanine green (ICG) and paclitaxel (Tax) using zeolitic imidazolate frameworks-8 (ZIF-8) as a scaffold. This study aims to investigate the chemo-photothermal therapeutic potential of ZIF-8@ICG@Tax nanoparticles (NPs) in the treatment of non-small cell lung cancer (NSCLC). An “all-in-one” theranostic ZIF-8@ICG@Tax NPs was conducted by self-assembly based on electrostatic interaction. First, the photothermal effect, stability, pH responsiveness, drug release, and blood compatibility of ZIF-8@ICG@Tax were evaluated through in vitro testing. Furthermore, the hepatic and renal toxicity of ZIF-8@ICG@Tax were assessed through in vivo testing. Additionally, the anticancer effects of these nanoparticles were investigated both in vitro and in vivo. Uniform and stable chemo-photothermal ZIF-8@ICG@Tax NPs had been successfully synthesized and had outstanding drug releasing capacities. Moreover, ZIF-8@ICG@Tax NPs showed remarkable responsiveness dependent both on pH in the tumor microenvironment and NIR irradiation, allowing for targeted drug delivery and controlled drug release. NIR irradiation can enhance the tumor cell response to ZIF-8@ICG@Tax uptake, thereby promoting the anti-tumor growth in vitro and in vivo. ZIF-8@ICG@Tax and NIR irradiation have demonstrated remarkable synergistic anti-tumor growth properties compared to their individual components. This novel theranostic chemo-photothermal NPs hold great potential as a viable treatment option for NSCLC. Graphical Abstract
Studies have shown that addictive behavior is associated with many brain regions, such as the insula, globus pallidus, amygdala, nucleus accumbens, and midbrain dopamine system, but only a few studies have explored the role of the dorsal striatum in addictive behavior. In June 2020, we started contacting 608 patients who were hospitalized between January 2017 and December 2019, and we recruited 11 smoking addicts with dorsal striatum damage and 20 controls with brain damage that did not involve the dorsal striatum (the damaged areas included the frontal lobe, temporal lobe, parietal lobe, brain stem, thalamus, internal capsule, and so on). All study participants had brain damage due to acute cerebral infarction. Disruption of smoking addiction was found to be significantly associated with the dorsal striatum (Phi = 0.794770, P = 0.000015). Our findings suggested that patients in the dorsal striatum group were more likely to discontinue smoking than those in the non-dorsal striatum group. The characteristics of this interruption is that smoking can be quit more easily and quickly without recurrence and that the impulse to smoke is reduced. These results suggest that the dorsal striatum is a key area for addiction to smoking.
MicroRNAs (miRNAs) have been extensively studied over the decades and have been identified as potential molecular targets for cancer therapy. To date, many miRNAs have been found participating in the tumorigenesis of non-small cell lung cancer (NSCLC). The present study was designed to evaluate the functions of miR-125b-1-3p in NSCLC cells.MiR-125b-1-3p expression was detected in tissue samples from 21 NSCLC patients and in NSCLC cell lines using the real-time polymerase chain reaction. A549 cell lines were transfected with a miR-125b-1-3p mimic or miR-125b-1-3p antisense. Cell counting kit-8, wound healing, Matrigel invasion assays, and flow cytometry were used to assess the effects of these transfections on cell growth, migration, invasion, and apoptosis, respectively. Western blotting was used to detect apoptosis-related proteins, expression of S1PR1, and the phosphorylation status of STAT3. Significant differences between groups were estimated using Student's t-test or a one-way analysis of variance.MiR-125b-1-3p was downregulated in NSCLC samples and cell lines. Overexpression of miR-125b-1-3p inhibited NSCLC cell proliferation (37.8 ± 9.1%, t = 3.191, P = 0.013), migration (42.3 ± 6.7%, t = 6.321, P = 0.003), and invasion (57.6 ± 11.3%, t = 4.112, P = 0.001) and simultaneously induced more NSCLC cell apoptosis (2.76 ± 0.78 folds, t = 3.772, P = 0.001). MiR-125b-1-3p antisense resulted in completely opposite results. S1PR1 was found as the target gene of miR-125b-1-3p. Overexpression of miR-125b-1-3p inhibited S1PR1 protein expression (27.4 ± 6.1% of control, t = 4.083, P = 0.007). In addition, S1PR1 siRNA decreased STAT3 phosphorylation (16.4 ± 0.14% of control, t = 3.023, P = 0.015), as in cells overexpressing miR-125b-1-3p (16.7 ± 0.17% of control, t = 4.162, P = 0.026).Our results suggest that miR-125b-1-3p exerts antitumor functions in NSCLC cells by targeting S1PR1.miR-125-1-3p通过抑制S1PR1基因抑制非小细胞肺癌细胞摘要背景：微小RNA作为潜在的肿瘤治疗靶点目标，近年来引起了诸多研究者的关注。迄今为止，有诸多miRNA被发现在非小细胞肺癌(NSCLC)中起到重要作用。本次研究目的探索miR-125-1-3p在NSCLC中的作用及功能。 方法：MiR-125b-1-3p在21个NSCLC患者组织以及NSCLC细胞系中的表达水平采用RT-PCR进行检测。利用miR-125b-1-3p mimic 或者 miR-125b-1-3p antisense转染NSCLC A549细胞系用来过表达或沉默miR-125b-1-3p。CCK-8, 划痕实验，侵袭实验以及流式细胞分别用来检测miR-125b-1-3p对细胞增殖，迁移，侵入以及凋亡的影响。Western blotting用来检测凋亡相关蛋白，S1PR1蛋白以及STAT3蛋白的磷酸化状态。 结果：MiR-125b-1-3p在NSCLC组织以及细胞系中表达下调。过表达miR-125b-1-3p后可以抑制NSCLC细胞的增殖 (37.8 ± 9.1%, t = 3.191, P = 0.013)，迁移 (42.3 ± 6.7%, t = 6.321, P = 0.003) 以及侵袭 (57.6 ± 11.3%, t = 4.112, P = 0.001)。与此同时，过表达miR-125b-1-3p可以同时诱导NSCLC细胞凋亡 (2.76 ± 0.78 fold, t = 3.772, P = 0.001)。抑制miR-125b-1-3p则取得相反的表型结果。S1PR1被发现是miR-125b-1-3p的调控基因。过表达miR-125b-1-3p能够抑制S1PR1蛋白的表达 (27.4 ± 6.1% of control, t = 4.083, P = 0.007)。此外过表达miR-125b-1-3p (16.7 ± 0.17% of control, t = 4.162, P = 0.026) 以及沉默S1PR1蛋白 (16.4 ± 0.14% of control, t = 3.023, P = 0.015) 后能够抑制STAT3蛋白的磷酸化。 结论：我们的发现揭示了miR-125b-1-3能够通过抑制S1PR1，从而在NSCLC中起到抑癌基因的作用。.
Tetraspanin 2 (TSPAN2) belongs to the tetraspanin superfamily. Previous studies have identified significant associations of the TSPAN2 single nucleotide polymorphisms (SNPs) rs12134493 and rs2078371 with migraine in Western populations; however, these associations need to be confirmed in the Chinese Han population. In addition, we carried out further studies to see whether TSPAN2 is associated with susceptibility to migraine to provide new clinical evidence. A case-control study (425 patients with migraine and 425 healthy controls) in a Chinese Han population was performed to evaluate the associations between migraine and TSPAN2 via a genotype-phenotype analysis between TSPAN2 and clinical symptoms. The SNP rs2078371 was found to be significantly associated with migraines especially in migraines without aura (MO) and in female patients. Meta-analysis revealed that the A allele of rs12134493 was significantly associated with migraines (OR = 1.14, P = 0.0001). Our findings suggested that TSPAN2 is a potential susceptibility factor for migraines. To confirm our results, a large-scale Chinese Han population study should be conducted. Considering that these two SNPs have not been definitively shown to affect TSPAN2 or to regulate nearby genes in this genomic region, the biological function and molecular mechanism of TSPAN2 in migraine should be further explored.
Background. ceRNAs (competing endogenous RNAs) are a newly identified type of regulatory RNA.Accumulating evidence suggests that ceRNAs play an important role in the pathogenesis of diseases such as cancer.Thus, ceRNA dysregulation may represent an important molecular mechanism underlying cancer progression and poor prognosis.In this study, we aimed to identify ceRNAs that may serve as potential biomarkers for early diagnosis of lung adenocarcinoma (LUAD).Methods.We performed differential gene expression analysis on TCGA-LUAD datasets to identify differentially expressed (DE) mRNAs, lncRNAs, and miRNAs at different tumor stages.Based on the ceRNA hypothesis and considering the synergistic or feedback regulation of ceRNAs, a lncRNA-miRNA-mRNA network was constructed.Functional analysis was performed using GO term and KEGG pathway enrichment analysis and KOBAS 2.0 software.Transcription factor analysis was carried out to identify direct targets of the transcription factors associated with LUAD prognosis.Identified differentially expressed genes were validated using GEO datasets. Results.Based on analysis of TCGA-LUAD datasets, we obtained 2610 DE mRNAs, 915 lncRNAs, and 125 miRNAs that were common to different tumor stages (|log 2 (Fold change)| ≥ 1, FDR < 0.01), respectively.Functional analysis showed that the aberrantly expressed mRNAs were closely related to tumor development.Survival analyses of the constructed ceRNA network modules demonstrated that five of them exhibit prognostic significance.The five ceRNA interaction modules contained one lncRNA (FENDRR), three mRNAs (EPAS1, FOXF1, and EDNRB), and four miRNAs (hsa-miR-148a, hsa-miR-195, hsa-miR-196b, and hsa-miR-301b).The aberrant expression of one lncRNA and three mRNAs was verified in the LUAD GEO dataset.Transcription factor analysis demonstrated that EPAS1 directly targeted 13 DE mRNAs.Conclusion.Our observations indicate that lncRNA-related ceRNAs and TFs play an important role in LUAD.The present study provides novel insights into the molecular mechanisms underlying LUAD pathogenesis.Furthermore, our study facilitates the identification of potential biomarkers for the early diagnosis and prognosis of LUAD and therapeutic targets for its treatment.
Background. ceRNAs (competing endogenous RNAs) are a newly identified type of regulatory RNA.Accumulating evidence suggests that ceRNAs play an important role in the pathogenesis of diseases such as cancer.Thus, ceRNA dysregulation may represent an important molecular mechanism underlying cancer progression and poor prognosis.In this study, we aimed to identify ceRNAs that may serve as potential biomarkers for early diagnosis of lung adenocarcinoma (LUAD).Methods.We performed differential gene expression analysis on TCGA-LUAD datasets to identify differentially expressed (DE) mRNAs, lncRNAs, and miRNAs at different tumor stages.Based on the ceRNA hypothesis and considering the synergistic or feedback regulation of ceRNAs, a lncRNA-miRNA-mRNA network was constructed.Functional analysis was performed using GO term and KEGG pathway enrichment analysis and KOBAS 2.0 software.Transcription factor analysis was carried out to identify direct targets of the transcription factors associated with LUAD prognosis.Identified differentially expressed genes were validated using GEO datasets. Results.Based on analysis of TCGA-LUAD datasets, we obtained 2610 DE mRNAs, 915 lncRNAs, and 125 miRNAs that were common to different tumor stages (|log 2 (Fold change)| ≥ 1, FDR < 0.01), respectively.Functional analysis showed that the aberrantly expressed mRNAs were closely related to tumor development.Survival analyses of the constructed ceRNA network modules demonstrated that five of them exhibit prognostic significance.The five ceRNA interaction modules contained one lncRNA (FENDRR), three mRNAs (EPAS1, FOXF1, and EDNRB), and four miRNAs (hsa-miR-148a, hsa-miR-195, hsa-miR-196b, and hsa-miR-301b).The aberrant expression of one lncRNA and three mRNAs was verified in the LUAD GEO dataset.Transcription factor analysis demonstrated that EPAS1 directly targeted 13 DE mRNAs.Conclusion.Our observations indicate that lncRNA-related ceRNAs and TFs play an important role in LUAD.The present study provides novel insights into the molecular mechanisms underlying LUAD pathogenesis.Furthermore, our study facilitates the identification of potential biomarkers for the early diagnosis and prognosis of LUAD and therapeutic targets for its treatment.
Background. ceRNAs (competing endogenous RNAs) are a newly identified type of regulatory RNA.Accumulating evidence suggests that ceRNAs play an important role in the pathogenesis of diseases such as cancer.Thus, ceRNA dysregulation may represent an important molecular mechanism underlying cancer progression and poor prognosis.In this study, we aimed to identify ceRNAs that may serve as potential biomarkers for early diagnosis of lung adenocarcinoma (LUAD).Methods.We performed differential gene expression analysis on TCGA-LUAD datasets to identify differentially expressed (DE) mRNAs, lncRNAs, and miRNAs at different tumor stages.Based on the ceRNA hypothesis and considering the synergistic or feedback regulation of ceRNAs, a lncRNA-miRNA-mRNA network was constructed.Functional analysis was performed using GO term and KEGG pathway enrichment analysis and KOBAS 2.0 software.Transcription factor analysis was carried out to identify direct targets of the transcription factors associated with LUAD prognosis.Identified differentially expressed genes were validated using GEO datasets. Results.Based on analysis of TCGA-LUAD datasets, we obtained 2610 DE mRNAs, 915 lncRNAs, and 125 miRNAs that were common to different tumor stages (|log 2 (Fold change)| ≥ 1, FDR < 0.01), respectively.Functional analysis showed that the aberrantly expressed mRNAs were closely related to tumor development.Survival analyses of the constructed ceRNA network modules demonstrated that five of them exhibit prognostic significance.The five ceRNA interaction modules contained one lncRNA (FENDRR), three mRNAs (EPAS1, FOXF1, and EDNRB), and four miRNAs (hsa-miR-148a, hsa-miR-195, hsa-miR-196b, and hsa-miR-301b).The aberrant expression of one lncRNA and three mRNAs was verified in the LUAD GEO dataset.Transcription factor analysis demonstrated that EPAS1 directly targeted 13 DE mRNAs.Conclusion.Our observations indicate that lncRNA-related ceRNAs and TFs play an important role in LUAD.The present study provides novel insights into the molecular mechanisms underlying LUAD pathogenesis.Furthermore, our study facilitates the identification of potential biomarkers for the early diagnosis and prognosis of LUAD and therapeutic targets for its treatment.
Boonchoplasty can not only remove tumor but also reserve lung tissue maximally, and it becomes an alternative choice for patient with poor pulmonary function who could not accept pneumonectomy. The aim of this study is to summarize the experience of carinal resection and reconstruction, bronchoplasty and pulmonary arterioplasty in the treatment of central-type lung cancer.From March, 1987 to March, 2005, A total of 79 patients with central-type lung cancer underwent operation. The operations included: left bronchoplasty (34 cases) combined with pulmonary arterioplasty in 10 cases and partial resection of left atrium in 3 cases; right bronchoplasty (45 cases) combined with carinal resection in 14 cases and segmentplasty in 5 cases, pulmonary arterioplasty in 5 cases, partial resection of superior vena cava wall in 5 cases.There were no perioperative deaths. Twenty-eight cases (35.4%) had postoperative complication. The 1-, 3-and 5-year survival rate were 86.1%, 55.2% and 32.1% respectively.Proper selection of carinal resection, bronchoplasty and pulmonary arterioplasty can expand the indications. They can reduce the ratio of pneumonectomy and improve the postoperative quality of life and the prognosis of lung cancer patients.
Non-small-cell lung cancer (NSCLC) constitutes the leading cause of cancer death in humans. Previous studies revealed the essential role of the protein arginine methyltransferase 7 (PRMT7) in promoting metastasis in breast cancer. However, its function and potential mechanism in NSCLC remain unclear.The gene expression of PRMT7 between lung cancer tissues and normal tissues was studied with online database (http://medicalgenome.kribb.re.kr/GENT/). NSCLC cell lines with specific gene overexpression were constructed with lentivirus transduction. Matrigel invasion and colony formation assays were performed to evaluate the invasion and colony formation abilities. Co-immunoprecipitation coupled with mass spectrometry analysis was performed to explore the potential interaction proteins of PRMT7. Bioinformatic analysis was performed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases.Online analysis of gene expression patterns revealed the relatively high expression of PRMT7 in lung cancer tissues. PRMT7 overexpression was able to promote the invasion and colony formation of A549 and SPC-A1 cells. A total of 19 in-common proteins shared by both NSCLC cell lines were identified to be interacting with PRMT7 and found to participate in a wide variety of pathways and protein-protein interactions according to bioinformatic analysis. Among them, HSPA5 and EEF2 were further investigated for their essential roles in PRMT7-promoted NSCLC cell invasion.Our results suggested PRMT7 overexpression was able to promote metastasis in NSCLC possibly through the interaction with HSPA5 and EEF2, which provides the potential mechanism of oncogenesis in lung cancer.
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