Systematic analysis of cuproptosis abnormalities and functional significance in cancer.

BACKGROUND: Cuproptosis is a recently discovered type of cell death, but the role and behavior of cuproptosis-related genes (CuRGs) in cancers remain unclear. This paper aims to address these issues by analyzing the multi-omics characteristics of cancer-related genes (CuRGs) across various types of cancer. METHOD: To investigate the impact of somatic copy number alterations (SCNA) and DNA methylation on CRG expression, we will analyze the correlation between these factors. We developed a cuproptosis index (CPI) model to measure the level of cuproptosis and investigate its functional roles. Using this model, we assessed the clinical prognosis of colorectal cancer patients and analyzed genetic changes and immune infiltration features in different CPI levels. RESULTS: The study's findings indicate that the majority of cancer-related genes (CuRGs) were suppressed in tumors and had a positive correlation with somatic copy number alterations (SCNA), while having a negative correlation with DNA methylation. This suggests that both SCNA and DNA methylation have an impact on the expression of CuRGs. The CPI model is a reliable predictor of survival outcomes in patients with colorectal cancer and can serve as an independent prognostic factor. Patients with a higher CPI have a worse prognosis. We conducted a deeper analysis of the genetic alterations and immune infiltration patterns in both CPI positive and negative groups. Our findings revealed significant differences, indicating that CuRGs may play a crucial role in tumor immunity mechanisms. Additionally, we have noticed a positive correlation between CuRGs and various crucial pathways that are linked to the occurrence, progression, and metastasis of tumors. CONCLUSIONS: Overall, our study systematically analyzes cuproptosis and its regulatory genes, emphasizing the potential of using cuproptosis as a basis for cancer therapy.

MAGP1 maintains tumorigenicity and angiogenesis of laryngeal cancer by activating Wnt/ß-catenin/MMP7 pathway.

Microfibril-associated glycoprotein-1 (MAGP1), a crucial extracellular matrix protein, contributes to the initiation and progression of different cancers. However, the role of MAGP1 in laryngeal cancer is not clear. The purpose of this study was to investigate the clinical significance and biological function of MAGP1 in laryngeal cancer. MAGP1 was upregulated in public databases and laryngeal cancer tissues, and high MAGP1 expression led to a poor prognosis and was identified as an independent prognostic marker. Knocking-down MAGP1 inhibited laryngeal cancer cell growth and metastasis. According to gene set enrichment analysis, high MAGP1 expression revealed enrichment in Wnt/ß-catenin signaling and knocking-down MAGP1 in laryngeal cancer cells also caused degradation, de-activation, re-location and loss of stability of ß-catenin. Additionally, we observed MAGP1 in laryngeal cancer cells inhibits angiogenesis in an MMP7-dependent way. In conclusion, our study suggests a clinical role of MAGP1 in laryngeal cancer, signifying its potential as a therapeutic target in the future.

Colonic stent as a bridge to surgery versus emergency rection for malignant left-sided colorectal obstruction: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: The role of self-expanding metal stent (SEMS) implantation as a bridge to surgery in malignant left-sided colorectal obstruction (MLCO) remains controversial. OBJECTIVE: To evaluate the safety of SEMS implantation versus emergency surgery (ER) in the treatment of MLCO. METHODS: Four major literature databases (Cochrane Library, Embase, PubMed, and Web of Science) were searched to collect articles published before April 20, 2023. After determining random or fixed-effect models based on heterogeneity tests, odds ratios (RR) or standardized mean differences (SMD) with their respective 95% confidence intervals (CI) were calculated. RESULTS: Nineteen randomized controlled studies were included. The main outcomes included overall tumor recurrence rate, 30-day mortality rate, and overall incidence of complications. Secondary outcomes included mortality-related indicators, tumor recurrence-related indicators, surgery-related indicators, and other relevant indicators. The study found that there was no significant difference in the 30-day mortality rate between the SEMS group and the er group. However, the SEMS group had a lower overall incidence of complications (RR = 0.787, P = .004), lower incision infection rate (RR = 0.472, P = .003), shorter operation time (SMD = -0.591, P = .000), lower intraoperative blood loss (SMD = -1.046, P = .000), lower intraoperative transfusion rate (RR = 0.624, P = .021), lower permanent stoma rate (RR = 0.499, P = .000), lower overall stoma rate (RR = 0.520,P = .000), shorter hospital stay (SMD = -0.643, P = .014), and more lymph node dissections during surgery (SMD = 0.222, 95% CI: 0.021-0.423, P = .031), as well as a higher primary anastomosis rate (RR = 0.472, 95% CI: 0.286-0.7 77, P = .003), among other advantages. However, the SEMS group had a higher overall tumor recurrence rate (RR = 1.339, P = .048). CONCLUSION: SEMS has significant advantages over er in relieving clinical symptoms and facilitating postoperative recovery in MLCO, but does not reduce the tumor recurrence rate. Neoadjuvant chemotherapy combined with SEMS may provide a new approach to the treatment of MLCO.

Exploring the dynamics of perioperative symptom networks in colorectal cancer patients: a cross-lagged panel network analysis.

BACKGROUND: Colorectal cancer incidence is on the rise, necessitating precise symptom management. However, causal relationships among symptoms have been challenging to establish due to reliance on cross-sectional data. Cross-lagged panel network (CLPN) analysis offers a solution, leveraging longitudinal data for insight. OBJECTIVE: We employed CLPN analysis to construct symptom networks in colorectal cancer patients at three perioperative time points, aiming to identify predictive relationships and intervention opportunities. METHODS: We evaluated the prevalence and severity of symptoms throughout the perioperative period, encompassing T1 the first day of admission, T2 2-3 days postoperatively, and T3 discharge, utilizing the M. D. Anderson Symptom Inventory Gastrointestinal Cancer Module (MDASI-GI). To identify crucial nodes in the network and explore predictive and interactive effects among symptoms, CLPNs were constructed from longitudinal data in R. RESULTS: The analysis revealed a stable network, with disturbed sleep exhibiting the highest out-EI (outgoing expected influence) during T1. Distress had a sustained impact throughout the perioperative. Disturbed sleep at T1 predicted T2 bloating, fatigue, distress, and pain. T1 distress predicted T2 sadness severity. T2 distress primarily predicted T3 fatigue, disturbed sleep, changes in taste, and bloating. T2 shortness of breath predicted T3 changes in taste and loss of appetite. Furthermore, biochemical markers like RBC and ALB had notable influence on symptom clusters during T1→T2 and T2→T3, respectively. CONCLUSION: Prioritizing disturbed sleep during T1 and addressing distress throughout the perioperative phase is recommended. Effective symptom management not only breaks the chain of symptom progression, enhancing healthcare impact, but also eases patient symptom burdens.

Diagnostic value of endoscopic ultrasonography in periampullary duodenal tumours.

Introduction: The objective of this study was to investigate the diagnostic value of endoscopic ultrasonography (EUS) for tumours around the duodenal ampullary. Patients and Methods: A retrospective analysis was performed on cases diagnosed and treated in our hospital from October 2016 to August 2021 due to the lesions around the duodenal ampulla. All patients received EUS, abdominal enhanced computed tomography (CT) and magnetic resonance imaging combined with magnetic resonance cholangiopancreatography (MRI-MRCP). Pathological diagnosis was used to verify the accuracy of the imaging findings. The detection rates of periampullary tumours by EUS, abdominal enhanced CT and MRI-MRCP were determined and compared. Results: A total of 86 patients were included in this study. According to the pathological diagnosis, the detection rate of EUS was 87% (36/41) for periampullary tumour lesions with a tumour diameter <1 cm, which was significantly higher than that of MRI-MRCP (59%, 24/41) (P = 0.003) and CT (44%, 18/41) (P < 0.001). For periampullary tumour lesions with a tumour diameter ≥1 cm, the detection rate of MRI-MRCP was 93% (42/45), which was significantly higher than that of EUS (78%, 35/45) (P = 0.036) and CT (76%, 34/45) (P = 0.02). Conclusions: EUS can accurately detect tumour lesions around the ampullary part of the duodenum with minimal gas interference. For periampullary tumour lesions <1 cm, EUS has better diagnostic accuracy than abdominal-enhanced CT and MRI-MRCP. In addition, a biopsy of the lesion can be performed at the same time during the EUS examination. Therefore, EUS has an important clinical significance and value in the diagnosis of duodenal periampullary tumours.

Study on sentinel symptoms and influencing factors of postoperative chemotherapy in patients with gastric cancer.

PURPOSE: To explore the symptom clusters of gastric cancer patients receiving postoperative chemotherapy, identify the sentinel symptom of each symptom cluster, and compare the differences in sentinel symptoms of patients for gastric cancer with different characteristics. METHODS: This was a cross-sectional study. Patients with postoperative gastric cancer who received chemotherapy in the medical oncology department from October 2021 to July 2022 were selected for the study using a convenience sampling method.The General Information Questionnaire and the MD Anderson Symptom Inventory Gastrointestinal Cancer (MDASI-GI) were used for the survey. RESULTS: A total of 245 patients participated in the study. There were five symptom clusters in the patients. Fatigue, nausea, sadness, and taste alteration were the sentinel symptoms of the disease symptom cluster, gastrointestinal symptom cluster, emotional symptom cluster, and neurotoxic symptom cluster, respectively. No clear sentinel symptom was found in the gastric-cancer-specific symptom cluster. Statistically significant differences were observed in fatigue, nausea, sadness, and taste alteration among patients receiving postoperative chemotherapy for gastric cancer with differences in gender, duration since diagnosis, tumor site, chemotherapy regimen, chemotherapy cycle, red blood cell count, hemoglobin level, albumin level, plasma D-dimer level, indirect bilirubin level, glutamic pyruvic transaminase level, total bile acid level, and uric acid level. CONCLUSION: People with postoperative chemotherapy for gastric cancer experience multiple concurrent symptoms. Of the multiple symptoms that occur simultaneously, patients tend to focus on 1 or 2 symptoms of particular significance and use the occurrence of 1 symptom to explain the others. The understanding of symptom clusters and sentinel symptoms could be beneficial to assess and manage both in postoperative patients with gastric cancer during chemotherapy. Clinical staff should use sentinel symptoms as the targets for symptom cluster evaluation and effective intervention.

circ_0006089 Facilitates Gastric Cancer Progression via Decoying miR- 515-5p and Up-regulating CXCL6.

BACKGROUND: Gastric cancer (GC) is the most common cancer globally. Recent research has suggested that circular RNAs (circRNAs) play crucial roles in GC tumorigenesis and progression. The present study is performed to clarify the possible mechanism of circRNA has_circ_0006089 (circ_0006089) in GC. METHODS: The differentially expressed circRNAs were screened out by analyzing the dataset GSE83- 521. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect circ_0006089, miR-515-5p and CXCL6 expression levels in GC tissues and cell lines. CCK-8, BrdU and Transwell assays were adopted to examine the biological function of circ_0006089 in GC cells. The interaction between miR-515-5p and circ_0006089, as well as between CXCL6 and miR-515-5p, was confirmed through bioinformatics, RNA immunoprecipitation (RIP) assay, dual-luciferase reporter gene assay and RNA pull-down assay. RESULTS: Circ_0006089 was significantly upregulated in GC tissues and cells, and miR-515-5p was remarkably downregulated. After knocking down circ_0006089 or overexpressing miR-515-5p, the growth, migration and invasion of GC cells were markedly reduced. In terms of mechanism, miR-515- 5p was verified to be the target of circ_0006089, and CXCL6 was validated as miR-515-5p's downstream target gene. Inhibiting miR-515-5p reversed the inhibitory effect knocking down circ_0006089 had on GC cell proliferation, migration and invasion. CONCLUSION: Circ_0006089 facilitates the malignant biological behaviors of GC cells via the miR-515- 5p/CXCL6 axis. Circ_0006089 can probably act as one of the important biomarkers and therapeutic targets in GC treatment strategies.

Establishment and validation of nomogram for predicting immuno checkpoint inhibitor related pneumonia.

OBJECTIVE: Cancer is one of the main causes of death worldwide. Although immunotherapy brings hope for cancer treatment, it is also accompanied by immune checkpoint inhibitor-related adverse events (irAEs). Immune checkpoint inhibitor pneumonia (CIP) is a potentially fatal adverse event, but there is still a lack of effective markers and prediction models to identify patients at increased risk of CIP. METHODS: A total of 369 cancer patients treated between 2017 and 2022 with immune checkpoint inhibitors at Shengjing Hospital of China Medical University and Liaoning People's Hospital were recruited for this study. Independent variables were selected by differences and binary logistic regression analysis, and a risk assessment nomogram was constructed for CIP risk. The accuracy and discriminative abilities of the nomogram were evaluated by calibration plots, receiver operating characteristic curves (ROCs) and decision curve analyses (DCAs). RESULTS: Binary logistic regression analysis showed that smoking history, acute phase proteins [interleukin (IL-6) and C-reactive protein (CRP)], CD8 + T lymphocyte count and serum alveolar protein [surface protein-A (SP-A) and Krebs Von den Lungen-6 (KL-6)] were significantly associated with CIP risk. A nomogram consisting of these variables was established and validated by different analyses. CONCLUSIONS: We developed an effective risk nomogram for CIP prediction in immune-checkpoint inhibitor administrated cancer patients, which will further assist early detection of immunotherapy-related adverse events.

Lycorine inhibits angiogenesis by docking to PDGFRα.

Lycorine (Lyc) is a natural alkaloid derived from medicinal plants of the Amaryllidaceae family. Lyc has been reported to inhibit the recurrence and metastasis of different kinds of tumors. However, Lyc's effect on angiogenesis and its specific mechanism are still not clear. This study was designed to test the antiangiogenesis effect of Lyc and to explore the possible mechanisms. We performed cell experiments to confirm Lyc's inhibitory effect on angiogenesis and employed sunitinib as a positive control. Moreover, the synergistic effect of Lyc and sunitinib was also explored. Next, we conducted bioinformatics analyses to predict the potential targets of Lyc and verified them by western blotting and immunofluorescence. Molecular docking, kinase activity assays, Biacore assays and cellular thermal shift assays (CETSAs) were applied to elucidate the mechanism by which Lyc inhibited target activity. Lyc inhibited angiogenesis in human umbilical vein endothelial cells (HUVECs). Employing bioinformatics, we found that Lyc's target was PDGFRα and that Lyc attenuated PDGFRα phosphorylation. We also found that Lyc inhibited PDGFRα activation by docking to it to restrain its activity. Additionally, Lyc significantly inhibited PDGF-AA-induced angiogenesis. This study provides new insights into the molecular functions of Lyc and indicates its potential as a therapeutic agent for tumor angiogenesis.

A Molten-Salt Method to Synthesize Ultrahigh-Nickel Single-Crystalline LiNi0.92 Co0.06 Mn0.02 O2 with Superior Electrochemical Performance as Cathode Material for Lithium-Ion Batteries.

Ni-rich layered oxides have been intensively considered as promising cathode materials for next-generation Li-ion batteries. Nevertheless, the performance degradation caused by intergranular cracks and electrode/electrolyte interface parasitic reactions restricts their further application. Compared with secondary particles, single-crystal (SC) materials have better mechanical integrity and cycling stability. However, the preparation of ultrahigh-nickel layered SC cathode still remains a serious challenge. Herein, a novel LiOH-LiNO3 -H3 BO3 molten-salt method is proposed to synthesize SC LiNi0.92 Co0.06 Mn0.02 O2 with considerable crystallinity and uniformity. The critical impacts of calcination temperature and boric acid on the microstructure and electrochemical property of Ni-rich layered oxides are systematically investigated. The results show that the crystal growth is promoted and the stability of crystal structure is improved by this synthesis method. In particular, the optimal electrode demonstrates a superior initial discharge capacity of 214.8 mAh g-1 with a high capacity retention of 86.3% over 300 cycles as tested by pouch-type full cells at 45 ºC. This work not only prepares an ultrahigh-nickel layered CS cathode with superior electrochemical performances, but also provides a feasible method for the synthesis of other CS layered cathode materials.

An extraction from Trametes robiniophila Murr. (Huaier) inhibits non-small cell lung cancer proliferation via targeting to epidermal growth factor receptor.

An extraction from Trametes robiniophila Murr. (Huaier) is a kind of natural fungus growing from the sophora japonica tree. Huaier is widely applied to cure the hepatocellular cancer (HCC). However, the medicinal fungus' curative result on non-small-cell lung cancer (NSCLC) is not well elaborated. In this study, we applied in vitro experiments to study Huaier's curative result on NSCLC. The potential Huaier targets were predicted using bioinformatics and validated by western blotting. We further elucidated the mechanism of Huaier targeting by molecular docking, kinase activity assay, CEllular Thermal Shift Assays (CETSAs). At last, in vivo curative result was verified further. Huaier weakened proliferation and promoted apoptosis of the NSCLC cell lines. According to bioinformatics, Epidermal Growth Factor Receptor (EGFR) may be the target of Huaier. Western blotting showed that Huaier can attenuate the activation of EGFR and we found that Huaier can dock to EGFR. Huaier significantly inhibited the tumor growth by weakening the expression of p-EGFR in vivo. This study offers a new idea for further understanding of Huaier and shows its potential as a therapeutic agent.

Knockdown of long noncoding RNA growth arrest-specific transcript 5 regulates forkhead box O3 to inhibit lipopolysaccharide-induced human bronchial epithelial cell pyroptosis.

Pyroptosis is a novel proinflammatory programmed cell death process. This study was designed to investigate the functional mechanisms of long noncoding RNA growth arrest-specific transcript 5 (lncRNA GAS5) on lipopolysaccharide (LPS)-induced human bronchial epithelial cell (HBEC) pyroptosis. LPS was used to induce pyroptosis in HBECs, followed by the detection of the expression of GAS5, forkhead box O3 (FOXO3), and nuclear factor E2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) signaling pathway-related factors. Cell viability was evaluated using CCK-8 assay, lactate dehydrogenase (LDH) release was assessed by LDH assay kit and caspase-1 activity by flow cytometry. Furthermore, expression of NOD-like receptor family pyrin domain containing 3 and pyroptosis-related proteins was evaluated using Western blot analysis, while enzyme-linked immunosorbent assay was used to determine the levels of inflammatory factors. The interaction between GAS5 and FOXO3 was confirmed using bioinformatic prediction, RNA immunoprecipitation assay, RNA pull-down, and dual-luciferase reporter gene assay. Treatment of HBECs with LPS upregulated the expression of GAS5 and FOXO3, resulting in the inactivation of the Nrf2/HO-1 signaling pathway. On the other hand, inhibition of both GAS5 and FOXO3 promoted cell viability, reduced LDH release, pyroptosis, and inflammatory response in LPS-induced HBECs. Furthermore, FOXO3 could interact with GAS5, while FOXO3 overexpression reversed the inhibitory effect of GAS5 knockdown on cell pyroptosis. Thus, mechanistically, inhibition of FOXO3 activates the Nrf2/HO-1 pathway to suppress LPS-induced pyroptosis in HBECs. This study revealed that GAS5 knockdown attenuates FOXO3 expression thereby activating the Nrf2/HO-1 pathway to inhibit LPS-induced pyroptosis in HBECs. These findings may contribute to identifying novel targets that inhibit pyroptosis in HBECs.

The CYP19A1 rs700519 Polymorphism and Breast Cancer Susceptibility in China: A Case-Control Study and Updated Meta-Analysis.

Objective: Breast cancer (BC), the most prevalent cancer in women, has been associated with several genetic factors, including the CYP19A1 rs700519 polymorphism; however, the conclusions have not been consistent. This case-control study and meta-analysis aimed to further assess the relationship between the CYP19A1 rs700519 polymorphism and BC susceptibility. Materials and Methods: We conducted a case-control study to assess the relationship of the CYP19A1 rs700519 polymorphism with the risk and prognosis of BC. Subsequently, we performed a meta-analysis of the case-control studies. Results: In the case-control study, we found a significant negative relationship between the rs700519 AA genotype and risk (χ2 = 7.503, p < 0.01) and disease-free survival rates (hazard rate = 0.400, 95% confidence interval [CI] = 0.181-0.883, p < 0.01) of patients with BC, especially in postmenopausal hormone receptor-positive (HR+) patients. Nine case-control studies were included in the meta-analysis. The CYP19A1 rs700519 polymorphism was significantly associated with BC susceptibility in the dominant (odds ratio [OR] = 0.95, 95% CI = 0.90-1.00, p = 0.05) and allelic models (OR = 0.84, 95% CI = 0.75-0.93, p < 0.01), but not in the recessive model. Sensitivity analysis revealed that the study results were stable, whereas the funnel plot revealed some publication bias. Conclusions: The CYP19A1 rs700519 polymorphism is related to breast tumorigenesis.

The effects of different repair methods for a posterior root tear of the lateral meniscus on the biomechanics of the knee: a finite element analysis.

PURPOSE: To explore the impact of different repair methods for a lateral meniscus posterior root tear on the biomechanics of the knee joint using finite element analysis. METHODS: Finite element models of a healthy knee were established on the basis of MRI data from a volunteer using Mimics software, and the validity of the models was tested. The changes in the contact mechanics and kinematics of these finite element models under different repair approaches were then analyzed and compared. RESULTS: The normal meniscus had the maximum joint contact area, the minimum contact pressure, and the minimum contact stress. When total meniscectomy of the lateral meniscus was performed, the lateral compartment had the minimum joint contact area, the maximum contact pressure and the maximum contact stress. When complete avulsions of the posterior root of the lateral meniscus occurred, the maximum values of contact pressure and contact stress were between those of an intact meniscus and those of a meniscus treated with total meniscectomy. Lateral meniscal root attachment reconstruction by the single-stitch and double-stitch techniques resulted in a significant decrease in joint contact pressure and contact stress, leading to values comparable to those of a normal knee joint, and the double-stitch technique performed better than the single-stitch technique. CONCLUSIONS: Repair surgery for lateral meniscal posterior root avulsions can effectively restore the contact mechanics and kinematics of the knee joint, and the double-stitch technique can result in better clinical outcomes than the single-stitch technique.

Pan-Cancer Analysis of NOS3 Identifies Its Expression and Clinical Relevance in Gastric Cancer.

Background: NOS3 (endothelial NOS, eNOS) is a member of the nitric oxide synthase (NOS) enzyme family, mainly participating in nitric oxide (NO) generation. NOS3 has been reported to inhibit apoptosis and promote angiogenesis, proliferation, and invasiveness. However, the expression pattern of NOS3 and its diagnostic and prognostic potential has not been investigated in a pan-cancer perspective. Methods: Data from the Genotype-Tissue Expression (GTEx), the Cancer Genome Atlas (TCGA), the Cancer Cell Line Encyclopedia (CCLE), and the Cancer Therapeutics Response Portal (CTRP) were employed and NOS3 expression was comprehensively analyzed in normal tissues, cancer tissues, and cell lines. Immunohistochemical staining of tissue sections were used to validate the prognostic role of NOS3 in gastric cancer patients. GSVA and GSEA analyses were performed to investigate signaling pathways related to NOS3 expression. Results: In normal tissues, NOS3 was expressed highest in the spleen and lowest in the blood. NOS3 expression was increased in stomach adenocarcinoma (STAD) and significantly associated with poor prognosis of patients. Immunohistochemical staining validated that NOS3 was an independent prognostic factor of gastric cancer. Several canonical cancer-related pathways were found to be correlated with NOS3 expression in STAD. The expression of NOS3 was related to the response to QS-11 and brivinib in STAD. Conclusions: NOS3 was an independent prognostic factor for patients with STAD. Increased expression of NOS3 influenced occurrence and development of STAD through several canonical cancer-related pathways. Drug response analysis reported drugs to suppress NOS3. NOS3 might be a novel target for gastric cancer treatment.

hiPSC-derived NSCs effectively promote the functional recovery of acute spinal cord injury in mice.

BACKGROUND: Spinal cord injury (SCI) is a common disease that results in motor and sensory disorders and even lifelong paralysis. The transplantation of stem cells, such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), or subsequently generated stem/progenitor cells, is predicted to be a promising treatment for SCI. In this study, we aimed to investigate effect of human iPSC-derived neural stem cells (hiPSC-NSCs) and umbilical cord-derived MSCs (huMSCs) in a mouse model of acute SCI. METHODS: Acute SCI mice model were established and were randomly treated as phosphate-buffered saline (PBS) (control group), repaired with 1 × 105 hiPSC-NSCs (NSC group), and 1 × 105 huMSCs (MSC group), respectively, in a total of 54 mice (n = 18 each). Hind limb motor function was evaluated in open-field tests using the Basso Mouse Scale (BMS) at days post-operation (dpo) 1, 3, 5, and 7 after spinal cord injury, and weekly thereafter. Spinal cord and serum samples were harvested at dpo 7, 14, and 21. Haematoxylin-eosin (H&E) staining and Masson staining were used to evaluate the morphological changes and fibrosis area. The differentiation of the transplanted cells in vivo was evaluated with immunohistochemical staining. RESULTS: The hiPSC-NSC-treated group presented a significantly smaller glial fibrillary acidic protein (GFAP) positive area than MSC-treated mice at all time points. Additionally, MSC-transplanted mice had a similar GFAP+ area to mice receiving PBS. At dpo 14, the immunostained hiPSC-NSCs were positive for SRY-related high-mobility-group (HMG)-box protein-2 (SOX2). Furthermore, the transplanted hiPSC-NSCs differentiated into GFAP-positive astrocytes and beta-III tubulin-positive neurons, whereas the transplanted huMSCs differentiated into GFAP-positive astrocytes. In addition, hiPSC-NSC transplantation reduced fibrosis formation and the inflammation level. Compared with the control or huMSC transplanted group, the group with transplantation of hiPSC-NSCs exhibited significantly improved behaviours, particularly limb coordination. CONCLUSIONS: HiPSC-NSCs promote functional recovery in mice with acute SCI by replacing missing neurons and attenuating fibrosis, glial scar formation, and inflammation.

Bufalin inhibits human diffuse large B-cell lymphoma tumorigenesis by inducing cell death through the Ca2+/NFATC1/cMYC pathway.

The 5-year survival rate of diffuse large B-cell lymphoma (DLBCL) can reach 60%. However, nearly half of patients undergo relapse/refractory issues with a survival period of less than 2 years. New therapeutic approaches are therefore needed to improve chemotherapy efficacy and patient survival. Bufalin (BF), isolated from the traditional Chinese medicine Chansu, has been reported to play an anticancer role in multiple cancer cell types. However, there are few reports of the effects of BF on the growth of DLBCL. In the present study, we demonstrated that BF exerts antitumor activity in DLBCL cells, both in vitro and in vivo. Treatment of DLBCL cells with BF resulted in increased proliferation and apoptosis in a dose- and time-dependent manner. Daily intraperitoneal injection of 1.5 mg/kg BF significantly delayed DLBCL xenograft growth in NOD/SCID mice without affecting body weight. Bioinformatics analysis showed that BF may regulate NFATC1 protein and affect expression of its downstream gene, cMYC. Our results suggest that BF can attenuate NFATC1 translocation by reducing the intracellular calcium concentration; BF may also have a low synergistic effect with cyclosporin A. In conclusion, we demonstrated that BF exerts antitumor activity that is mediated at least in part by the Ca2+/NFATC1/cMYC pathway. Our findings suggest that BF can be effectively applied as a novel potential therapeutic agent for DLBCL.

High SYT7 expression is associated with poor prognosis in human non-small cell lung carcinoma.

Synaptotagmin 7 (SYT7) can encode a single-pass 46-kDa transmembrane protein which located on human chromosome 11q12.2. It has been reported to be dysregulated in several cancers; however, there are few reports on the role of SYT7 in non-small cell lung carcinoma (NSCLC). The purpose of our study was to investigate the expression of SYT7 in NSCLC and its relationship with the prognosis of NSCLC. Differences in SYT7 expression were explored by using a public database and tissue samples. The prognostic value of SYT7 and its expression correlation with clinical parameters were evaluated by statistical analysis. Our current study found that elevated mRNA and protein levels of SYT7 in NSCLC tissues compared to adjacent normal tissues. The high expression of SYT7 in NSCLC patients was positively correlated with tumour differentiation (P = 0.031) and pT (P = 0.041). The higher SYT7 expression had a shorter survival time than those with lower SYT7 expression in NSCLC patients. Furthermore, multivariate analysis demonstrated that the expression of SYT7 was an unfavourable independent prognostic factor for NSCLC (P = 0.044). In conclusion, SYT7 was upregulated in NSCLC tissues and maybe a prognostic and diagnostic factor of NSCLC.

Piperlongumine inhibits head and neck squamous cell carcinoma proliferation by docking to Akt.

Piperlongumine (PL) is a biologically active alkaloid isolated from the long pepper roots and widely used as a traditional medicine in Ayurvedic medicine. However, the mechanism of PL's effect on head and neck squamous cell carcinoma (HNSCC) is not well understood. We performed cell experiments to confirm PL's inhibitory effect on HNSCC and employing cisplatin as positive control. Next, we conducted bioinformatics to predict PL's potential targets and verified by western blotting. Molecular docking, Biacore experiment and kinase activity assays were applied to elucidate the mechanism by which PL inhibited target activity. In vivo efficacy was verified by xenotransplantation and immunohistochemistry. PL inhibited proliferation, promoted late apoptosis, arrested cell cycle and inhibited DNA replication of the HEp-2 and FaDu cell lines. Employing bioinformatics, we found that PL's target was Akt and PL attenuated Akt phosphorylation. We found from molecular docking, Biacore experiment and kinase activity assay that PL inhibited Akt activation by docking to Akt to restrain its activity. In addition, PL significantly inhibited the growth of xenograft tumors by down regulating the expression of p-Akt in vivo. This study provides new insights into the molecular functions of PL and indicate its potential as a therapeutic agent for HNSCC.

Correction: Knockdown of MSI2 inhibits metastasis by interacting with caveolin-1 and inhibiting its ubiquitylation in human NF1-MPNST cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.