Enhanced anticancer activity by the combination of vinpocetine and sorafenib via PI3K/AKT/GSK-3ß signaling axis in hepatocellular carcinoma cells.

Vinpocetine is widely used to treat cerebrovascular diseases. However, the effect of vinpocetine to treat hepatocellular carcinoma (HCC) has not been investigated. In this study, we revealed that vinpocetine was associated with antiproliferative activity in HCC cells, but induced cytoprotective autophagy, which restricted its antitumor activity. Autophagy inhibitors improved the antiproliferative activity of vinpocetine in HCC cells. Sorafenib is effective to treat advanced HCC, but the effect of autophagy induced by sorafenib is indistinct. We demonstrated vinpocetine plus sorafenib suppressed the cytoprotective autophagy activated by vinpocetine in HCC cells and significantly induced apoptosis and suppressed cell proliferation in HCC cells. In addition, vinpocetine plus sorafenib activates glycogen synthase kinase 3ß (GSK-3ß) and subsequently inhibits cytoprotective autophagy induced by vinpocetine in HCC cells. Meanwhile, overexpression of GSK-3ß was efficient to increase the apoptosis induced by vinpocetine plus sorafenib in HCC cells. Our study revealed that vinpocetine plus sorafenib could suppress the cytoprotective autophagy induced by vinpocetine and subsequently show synergistically anti-HCC activity via activating GSK-3ß and the combination of vinpocetine and sorafenib might reverse sorafenib resistance via the PI3K/protein kinase B/GSK-3ß signaling axis. Thus, vinpocetine may be a potential candidate for sorafenib sensitization and HCC treatment, and our results may help to elucidate more effective therapeutic options for HCC patients with sorafenib resistance.

Association of the Collagen Signature in the Tumor Microenvironment With Recurrence and Survival of Patients With T4N0M0 Colon Cancer.

BACKGROUND: The current clinicopathological risk factors do not accurately predict disease recurrence in patients with T4N0M0 colon cancer. We hypothesized that the collagen signature combined with clinicopathological risk factors (new model) had a better prognostic value than clinicopathological risk factors alone (clinicopathological model). OBJECTIVE: This study aimed to establish a collagen signature in the tumor microenvironment and to validate its role in predicting the recurrence of T4N0M0 colon cancer. DESIGN: This was a retrospective study. SETTINGS: This study took place at a tertiary medical center. PATIENTS: Patients with T4N0M0 colon cancer who underwent surgery at our center between 2009 and 2015 (n = 416) were included. INTERVENTION: A total of 142 collagen features were analyzed in the tumor microenvironment in specimens of colon cancer by using second-harmonic generation imaging. A collagen signature was constructed using a least-absolute shrinkage and selection operator Cox regression model. MAIN OUTCOME MEASURES: The primary outcomes measured were disease-free survival and overall survival. RESULTS: The training and testing cohorts consisted of 291 and 125 randomly assigned samples, with recurrence rates of 19.9% and 22.4%. A 3-feature-based collagen signature predicted the recurrence risk at 1, 3, and 5 years, with the area under the receiver-operating characteristic curves of 0.808, 0.832, and 0.791 in the training cohort and 0.836, 0.807, and 0.794 in the testing cohort. Multivariate analysis revealed that the collagen signature could independently predict the disease-free survival (HR = 7.17, p < 0.001) and overall survival rates (HR = 5.03, p < 0.001). The new model had a better prognostic value than the clinicopathological model, which included 4 clinicopathological risk factors: obstruction or perforation, lymphovascular invasion, tumor budding, and no chemotherapy. LIMITATIONS: This study was limited by its retrospective design. CONCLUSIONS: The collagen signature in the tumor microenvironment may be a new prognostic marker that can effectively predict the recurrence and survival of patients with T4N0M0 colon cancer. See Video Abstract at http://links.lww.com/DCR/B503. ASOCIACIÓN DE LA RÚBRICA DE COLÁGENO EN EL MICROAMBIENTE TUMORAL CON LA RECIDIVA Y LA SOBREVIDA DE PACIENTES CON CÁNCER DE COLON T4N0M0: Los factores de riesgo clínico-patológicos actuales no predicen con precisión la recurrencia de la enfermedad en pacientes con cáncer de colon estadío T4N0M0. Presumimos que la rúbrica de colágeno combinada con factores de riesgo clínico-patológicos (nuevo modelo) tendrían un mejor valor pronóstico que los factores de riesgo clínico-patológicos solos (modelo clínico-patológico).El establecer una rúbrica de colágeno en el microambiente tumoral y validar su papel en la predicción de la recidiva del cáncer de colon T4N0M0.Estudio retrospectivo.Investigación llevada a cabo en un centro médico terciario.Se incluyeron pacientes con cáncer de colon T4N0M0 operados en nuestro centro entre 2009 y 2015 (n = 416).Se analizaron un total de 142 características de colágeno en el microambiente tumoral en muestras de cáncer de colon utilizando imágenes de segunda generación armónica. Se construyó una rúbrica de colágeno utilizando un modelo de regresión LASSO Cox.Sobrevida libre de enfermedad y sobrevida global.Las cohortes de entrenamiento y prueba consistieron en 291 y 125 muestras asignadas al azar, con tasas de recurrencia del 19,9% y 22,4%, respectivamente. La rúbrica del colágeno basada en 3 características predijo el riesgo de recurrencia a 1, 3 y 5 años, con el área bajo las curvas características operativas del receptor de 0,808, 0,832 y 0,791 en la cohorte de entrenamiento y 0,836, 0,807 y 0,794 en la cohorte de prueba, respectivamente. El análisis multivariado reveló que la firma de colágeno podría predecir de forma independiente la supervivencia libre de enfermedad (HR = 7,17, p <0,001) y las tasas de sobrevida general (HR = 5,03, p <0,001). El nuevo modelo tuvo un mejor valor pronóstico que el modelo clínico-patológico, que incluyó cuatro factores de riesgo clínico-patológicos: obstrucción o perforación, invasión linfovascular, gemación tumoral y ausencia de quimioterapia.Este estudio estuvo limitado por su diseño retrospectivo.La rúbrica de colágeno en el microambiente tumoral puede ser un nuevo marcador pronóstico para predecir eficazmente la recurrencia y la subrevida de los pacientes con cáncer de colon T4N0M0. Consulte Video Resumen en http://links.lww.com/DCR/B503. (Traducción-Dr. Xavier Delgadillo).

Laparoscopic resection is better than endoscopic dissection for gastric gastrointestinal stromal tumor between 2 and 5 cm in size: a case-matched study in a gastrointestinal center.

BACKGROUND: The feasibility of endoscopic dissection for gastric gastrointestinal stromal tumor (gGIST) between 2 and 5 cm in size has been demonstrated. However, its impact on short-term and long-term outcomes, compared with laparoscopic resection, is unknown. The purpose of this study was to compare short-term and long-term outcomes between laparoscopic resection and endoscopic dissection for 2-5-cm gGIST. METHODS: A case-matched study was performed using the propensity score. To overcome selection bias, we performed a 1:1 match using six covariates, including age, sex, BMI, ASA score, tumor size, and tumor location. Short-term and long-term outcomes between laparoscopic resection and endoscopic dissection were compared. RESULTS: A total of 210 patients with 2-5-cm gGIST were enrolled between 2006 and 2017 in our gastrointestinal center. According to the intention-to-treat approach, 165 patients underwent laparoscopic resection, and 45 patients underwent endoscopic dissection. After the propensity score, 45 pairs were balanced and analyzed. There was no significant difference in the baseline characteristics between the laparoscopic and endoscopic groups after matching. The rate of complications was significantly higher in the endoscopic group compared with the laparoscopic group (P < 0.001). Perforations occurred in 16 patients in the endoscopic group (16/45, 35.6%). The postoperative hospital stay was significantly longer in the endoscopic group compared with the laparoscopic group (P < 0.001). There was no significant difference between the two groups in disease-free survival or overall survival. CONCLUSION: Laparoscopic resection is better than endoscopic dissection for 2-5-cm gGIST because of the lower complication rate and shorter hospital stay.

Light-Switching Azo-Copolymers Self-Assembly in Multi-Stationary States.

In the present research, novel tri-block-copolymers bearing polyethylene glycol (PEG), azobenzene (Azo), and tetra-ortho-methoxy-substituted Azo (mAzo) segments are synthesized and explored. Light-controlled PEG-PmAzo-PAzo self-assemblies switching between multi-stationary states is realized. Under controlling of UV, blue, green, and red light, PEG-PmAzo-PAzo isomerize between 4 photostationary states. The enrichment of cis isomers of Azo and mAzo induces the self-assembly of PEG-PmAzo-PAzo in toluene. The morphologies and scale of the self-assemblies can be switched between four stationary states, which are investigated by dynamic light scattering, scanning electron microscopy, and transmission electron microscopy.

The lncRNA MACC1-AS1 promotes gastric cancer cell metabolic plasticity via AMPK/Lin28 mediated mRNA stability of MACC1.

BACKGROUND: Metabolic plasticity has been increasingly thought to be a determinant of tumor growth and metastasis. MACC1, a transcriptional regulator of MET, was recognized as an oncogene in gastric cancer (GC); however, its transcriptional or post-translational regulation was not clear. We previously reported the metabolic role of MACC1 in glycolysis to promote GC progression. MACC1-AS1 is the antisense lncRNA of MACC1, yet its function was previously unknown. METHODS: We profiled and analyzed the expression of MACC1-AS1 utilizing the TCGA database as well as in situ hybridization using 123 pairs of GC tissues and matched adjacent normal gastric mucosa tissues (ANTs). The biological role of MACC1-AS1 in cell growth and metastasis was determined by performing in vitro and in vivo functional experiments. Glycolysis and antioxidant capabilities were assayed to examine its metabolic function. Further, the specific regulatory effect of MACC1-AS1 on MACC1 was explored transcriptionally and post-transcriptionally. RESULTS: MACC1-AS1 was shown to be expressed significantly higher in GC tissues than in ANTs, which predicted poor prognosis in GC patients. MACC1-AS1 promoted GC cell proliferation and inhibited cell apoptosis under metabolic stress. Mechanistically, MACC1-AS1 stabilized MACC1 mRNA and post-transcriptionally augmented MACC1 expression. Further, MACC1-AS1 was shown to mediate metabolic plasticity through MACC1 upregulation and subsequent enhanced glycolysis and anti-oxidative capabilities, and this was suggested to be coordinated by the AMPK/Lin28 pathway. CONCLUSIONS: Elevated expression of MACC1-AS1 in gastric cancer tissues is linked to poor prognosis and promotes malignant phenotype upon cancer cells. MACC1-AS1 is elevated under metabolic stress and facilitates metabolic plasticity by promoting MACC1 expression through mRNA stabilization. Our study implicates lncRNA MACC1-AS1 as a valuable biomarker for GC diagnosis and prognosis.

Surface with Reversible Green-Light-Switched Wettability by Donor-Acceptor Stenhouse Adducts.

In this report, we designed surfaces with reversible green-light-switched wettability via donor-acceptor Stenhouse adducts (DASAs). Photoresponsive micro/nanoparticles were prepared by coating the surfaces of silica micro/nanoparticles with polydopamine and then postmodifying with DASA molecules. Then, the particles were immobilized on a glass substrate surfaces either with double-sided adhesive tape or cross-linking poly(dimethylsiloxane). Silica micro/nanoparticles with various diameters (0.2, 2.5, and 85 µm) were used to fabricate the photoresponsive surface. Green light irradiation switches the hydrophobic linear DASA to a hydrophilic cyclic isomer, which further increases the wettability and contact angle hysteresis on the surface. On the other hand, heating (100 °C) induces the cyclic-to-linear isomerization of DASA molecules and switches the surface back to hydrophobic. The wettability of the DASA-modified surface is reversible under alternate green light irradiation and heating.

ROS signaling under metabolic stress: cross-talk between AMPK and AKT pathway.

Cancer cells are frequently confronted with metabolic stress in tumor microenvironments due to their rapid growth and limited nutrient supply. Metabolic stress induces cell death through ROS-induced apoptosis. However, cancer cells can adapt to it by altering the metabolic pathways. AMPK and AKT are two primary effectors in response to metabolic stress: AMPK acts as an energy-sensing factor which rewires metabolism and maintains redox balance. AKT broadly promotes energy production in the nutrient abundance milieu, but the role of AKT under metabolic stress is in dispute. Recent studies show that AMPK and AKT display antagonistic roles under metabolic stress. Metabolic stress-induced ROS signaling lies in the hub between metabolic reprogramming and redox homeostasis. Here, we highlight the cross-talk between AMPK and AKT and their regulation on ROS production and elimination, which summarizes the mechanism of cancer cell adaptability under ROS stress and suggests potential options for cancer therapeutics.

Long Non-Coding RNA MEG3 Downregulation Triggers Human Pulmonary Artery Smooth Muscle Cell Proliferation and Migration via the p53 Signaling Pathway.

BACKGROUND/AIMS: Increasing evidence has demonstrated a significant role of long non-coding RNAs (lncRNAs) in diverse biological processes, and many of which are likely to have functional roles in vascular remodeling. However, their functions in pulmonary arterial hypertension (PAH) remain largely unknown. Pulmonary vascular remodeling is an important pathological feature of PAH, leading to increased vascular resistance and reduced compliance. Pulmonary artery smooth muscle cells (PASMCs) dysfunction is involved in vascular remodeling. Long noncoding RNAs are potential regulators of PASMCs function. Herein, we determined whether long noncoding RNA-maternally expressed gene 3 (MEG3) was involved in PAH-related vascular remodeling. METHODS: The arterial wall thickness was examined by hematoxylin and eosin (H&E) staining in distal pulmonary arteries (PAs) isolated from lungs of healthy volunteers and PAH patients. The expression level of MEG3 was analyzed by qPCR. The effects of MEG3 on human PASMCs were assessed by cell counting Kit-8 assay, BrdU incorporation assay, flow cytometry, scratch-wound assay, immunofluorescence, and western blotting in human PASMCs. RESULTS: We revealed that the expression of MEG3 was significantly downregulated in lung and PAs of patients with PAH. MEG3 knockdown affected PASMCs proliferation and migration in vitro. Moreover, inhibition of MEG3 regulated the cell cycle progression and made more smooth muscle cells from the G0/G1 phase to the G2/M+S phase and the process could stimulate the expression of PCNA, Cyclin A and Cyclin E. In addition, we found that the p53 pathway was involved in MEG3-induced smooth muscle cell proliferation. CONCLUSIONS: This study identified MEG3 as a critical regulator in PAH and demonstrated the potential of gene therapy and drug development for treating PAH.

Defining the cellular precursors to human breast cancer.

Human breast cancers are broadly classified based on their gene-expression profiles into luminal- and basal-type tumors. These two major tumor subtypes express markers corresponding to the major differentiation states of epithelial cells in the breast: luminal (EpCAM(+)) and basal/myoepithelial (CD10(+)). However, there are also rare types of breast cancers, such as metaplastic carcinomas, where tumor cells exhibit features of alternate cell types that no longer resemble breast epithelium. Until now, it has been difficult to identify the cell type(s) in the human breast that gives rise to these various forms of breast cancer. Here we report that transformation of EpCAM(+) epithelial cells results in the formation of common forms of human breast cancer, including estrogen receptor-positive and estrogen receptor-negative tumors with luminal and basal-like characteristics, respectively, whereas transformation of CD10(+) cells results in the development of rare metaplastic tumors reminiscent of the claudin-low subtype. We also demonstrate the existence of CD10(+) breast cells with metaplastic traits that can give rise to skin and epidermal tissues. Furthermore, we show that the development of metaplastic breast cancer is attributable, in part, to the transformation of these metaplastic breast epithelial cells. These findings identify normal cellular precursors to human breast cancers and reveal the existence of a population of cells with epidermal progenitor activity within adult human breast tissues.

The effectiveness of lifestyle interventions on ecological literacy: A contribution to the underlying mechanism in linguistic ecology.

In today's society, citizens' ecological literacy (ecoliteracy) is critical for their understanding of sustainable development. This study used a questionnaire designed to quantitatively assess ecoliteracy from a linguistic ecology perspective. First, an underlying mechanism model for ecoliteracy was designed based on the results of previous studies. Then, the ecoliteracy level assessment scores of Guiyang inhabitants were combined with the respondents' corresponding lifestyle characteristics to explore the effectiveness of interventions in affecting the participants' ecoliteracy levels. The results showed that the formation and development of ecoliteracy is a dynamic and circular process that revolves around variables of independent, dependent, mediating, moderating and control. The various factors in the model interact and operate evenly along a particular path. As for the level of lifestyle characteristics, participants' ecoliteracy levels had a statistically significant relationship with their attitudes regarding the importance of nature, participating in outdoor activities, and improving their ecoliteracy levels; as well as the frequencies regarding daily outdoor activity, the main activities in ecological areas, participation in volunteer activities, and use of ecological knowledge. The respondents with the highest levels of ecoliteracy had the most positive attitudes and engaged in ecological actions with the highest frequency. The lifestyle intervention features here are of great significance to the harmonious coexistence between humans and the natural environment and are also helpful for improving human health.

The learning curve for gasless transaxillary posterior endoscopic thyroidectomy for thyroid cancer: a cumulative sum analysis.

Gasless transaxillary posterior endoscopic thyroidectomy (GTPET) is a new approach for thyroid cancer. It allows en bloc resection of the thyroid and central lymph nodes. Few studies have reported on the learning curve for GTPET.We examined the learning curve of GTPET for thyroid cancer by cumulative sum (CUSUM) analysis by retrospectively analyzing patients who underwent hemithyroidectomy with ipsilateral central neck dissection between December 2020 and September 2021 at a tertiary medical center, including the first patient. Moving average analysis and sequential time-block analysis were used for validation. Data on the clinical factors between the two periods were compared. In the overall cohort, the average time for GTPET for thyroid cancer was 113.25 min to harvest an average of 6.4 central lymph nodes. The CUSUM curve of the operative time indicated an inflection point after 38 patients. Moving average analysis and sequential time-block analysis validated the number of procedures needed for GTPET proficiency. (124.05 min vs. 107.63 min for the unproficient period vs. proficient period, respectively; P < 0.001) The number of retrieved lymph nodes was not associated with a certain level of proficiency per the learning curve. The main complication during the surgeon's unproficient period was transient hoarseness (3/38), which was similar to that in their proficient period (2/73, p = 0.336). Proficiency in GTPET is associated with performing more than 38 procedures. Standard course training and instruction on careful management are required prior to introducing the procedure.

Development and validation of a collagen signature to predict the prognosis of patients with stage II/III colorectal cancer.

The tumor, nodes and metastasis (TNM) classification system provides useful but incomplete prognostic information and lacks the assessment of the tumor microenvironment (TME). Collagen, the main component of the TME extracellular matrix, plays a nonnegligible role in tumor invasion and metastasis. In this cohort study, we aimed to develop and validate a TME collagen signature (CSTME) for prognostic prediction of stage II/III colorectal cancer (CRC) and to compare the prognostic values of "TNM stage + CSTME" with that of TNM stage alone. Results indicated that the CSTME was an independent prognostic risk factor for stage II/III CRC (hazard ratio: 2.939, 95% CI: 2.180-3.962, p < 0.0001), and the integration of the TNM stage and CSTME had a better prognostic value than that of the TNM stage alone (AUC(TNM+CSTME) = 0.772, AUC TNM = 0.687, p < 0.0001). This study provided an application of "seed and soil" strategy for prognosis prediction and individualized therapy.

Assessing ecological literacy and its application based on linguistic ecology: a case study of Guiyang City, China.

To address the frequent emergence of ecological problems, ecology has intersected with various disciplines. From the perspective of linguistic ecology, ecological literacy is an important concept that combines the subjects of ecology and linguistics. It not only discusses ecological issues, but also establishes a linguistic framework. Here, we constructed a quantitative method of assessing ecological literacy from the perspective of linguistic ecology. Ecological literacy was divided into five parts: ecological knowledge literacy, ecological awareness literacy, ecological ethics literacy, ecological emotional literacy, and ecological behavioral literacy. Each of these was set with four quantitative indicators that were evaluated through eight questions. A case study was conducted to investigate the ecological literacy of the inhabitants of Guiyang City, one of China's top ten ecologically advanced cities. The results showed that the proposed assessment method was an effective way to evaluate the level of ecological literacy comprehensively. In the case analysis, the overall ecological literacy level of Guiyang inhabitants was relatively good, and the levels of the five specific dimensions of them in descending order were as follows: ecological ethics literacy, ecological emotional literacy, ecological awareness literacy, ecological knowledge literacy, and ecological behavioral literacy. The results of this study are conducive to the production of targeted ways to improve the level of ecological literacy for sustainable development.

Spatiotemporal cluster patterns of hand, foot, and mouth disease at the province level in mainland China, 2011-2018.

Although three monovalent EV-A71 vaccines have been launched in mainland China since 2016, hand, foot, and mouth disease (HFMD) still causes a considerable disease burden in China. Vaccines' use may change the epidemiological characters of HFMD. Spatial autocorrelation analysis and space-time scan statistics analysis were used to explore the spatiotemporal distribution pattern of this disease at the provincial level in mainland China. The effects of meteorological factors, socio-economic factors, and health resources on HFMD incidence were analyzed using Geodetector. Interrupted time series (ITS) was used to analyze the impact of the EV-A71 vaccine on the incidence of HFMD. This study found that the median annual incidence of HFMD was 153.78 per 100,000 (ranging from 120.79 to 205.06) in mainland China from 2011 to 2018. Two peaks of infections were observed per year. Children 5 years and under were the main morbid population. The spatial distribution of HFMD was presented a significant clustering pattern in each year (P<0.001). The distribution of HFMD cases was clustered in time and space. The range of cluster time was between April and October. The most likely cluster appeared in the southern coastal provinces (Guangxi, Guangdong, Hainan) from 2011 to 2017 and in the eastern coastal provinces (Shanghai, Jiangsu, Zhejiang) in 2018. The spatial heterogeneity of HFMD incidence could be attributed to meteorological factors, socioeconomic factors, and health resource. After introducing the EV-A71 vaccine, the instantaneous level of HFMD incidence decreased at the national level, and HFMD incidence trended downward in the southern coastal provinces and increased in the eastern coastal provinces. The prevention and control policies of HFMD should be adapted to local conditions in different provinces. It is necessary to advance the EV-A71 vaccination plan, expand the vaccine coverage and develop multivalent HFMD vaccines as soon as possible.

Invisible Inks for Secrecy and Anticounterfeiting: From Single to Double-encryption by Hydrochromic Molecules.

Secret information recorded by traditional single-encrypted invisible inks is easily cracked because the inks can switch only between "NONE" and "TRUTH". Developing double-encrypted systems makes the information reversibly switchable between "FALSE" and "TRUTH", which is helpful to ensure the safety of the secret information during transport. Here, we prepared heat-developed invisible inks by hydrochromic molecules donor-acceptor Stenhouse adducts (DASAs) and oxazolidines (OXs) and promoted the invisible inks from single to double encryption. DASAs coordinate with water molecules and form stable colorless cyclic DASA·xH2O molecules, which lose coordinated water molecules after heating and switch to colored linear DASAs. In contrast, OXs are colored with water and are colorless after heating. Single-encrypted secrecy was realized by DASA invisible inks. The information is invisible under the encrypted state and becomes bright purple after heating. Vapor treating re-encrypted the information in ∼5 min. Furthermore, the single-encryption was promoted to double-encryption by a DASA/OX invisible inks system. Heating and vapor treating switch the information between the "FALSE" and "TRUTH" reversibly. The DASA/OX invisible ink system is applied for secrecy of texts, graphic images, and quick response (QR) codes.

Immunohistochemical analysis supports a role for INI1/SMARCB1 in hereditary forms of schwannomas, but not in solitary, sporadic schwannomas.

The INI1/SMARCB1 protein product (INI1), a component of a transcription complex, was recently implicated in the pathogenesis of schwannomas in two members of a single family with familial schwannomatosis. Tumors were found to have both constitutional and somatic mutations of the SMARCB1 gene and showed a mosaic pattern of loss of INI1 expression by immunohistochemistry, suggesting a tumor composition of mixed null and haploinsufficient cells. To determine if this finding could be extended to all tumors arising in familial schwannomatosis, and how it compares with other multiple schwannoma syndromes [sporadic schwannomatosis and neurofibromatosis 2 (NF2)] as well as to sporadic, solitary schwannomas, we performed an immunohistochemistry analysis on 45 schwannomas from patients with multiple schwannoma syndromes and on 38 solitary, sporadic schwannomas from non-syndromic patients. A mosaic pattern of INI1 expression was seen in 93% of tumors from familial schwannomatosis patients, 55% of tumors from sporadic schwannomatosis, 83% of NF2-associated tumors and only 5% of solitary, sporadic schwannomas. These results confirm a role for INI1/SMARCB1 in multiple schwannoma syndromes and suggest that a different pathway of tumorigenesis occurs in solitary, sporadic tumors.

TRIM37 targets AKT in the growth of lung cancer cells.

BACKGROUND: TRIM37 is an ubiquitin E3 ligase. Growing evidence has demonstrated the high value of TRIM37 as a potential biomarker for diagnosis of certain cancers. However, the biological function of TRIM37 in lung cancer is still unknown. MATERIALS AND METHODS: In order to gain a deep insight into the function of TRIM37 in lung cancer cells, in the present study lentiviral vector was used to mediate RNA interference and overexpression of TRIM37 in lung cancer cells (H292, H358, and H1299). In addition, a specific AKT inhibitor LY294002 was utilized to examine the correlation between the expression of TRIM37 and AKT. RESULTS: TRIM37 acts as a positive regulator of cell proliferation in lung cancer cells. Moreover, cell apoptosis analyses showed the antiapoptosis function of TRIM37, which was mainly dependent on the regulation of BCL2 and BAX. Our results also indicated that AKT might be a target of TRIM37 in lung cancer cells. CONCLUSION: This research not only helps in understanding the molecular mechanisms of TRIM37 in detail but also provides evidence to develop novel biomarkers for lung cancer diagnosis.

Metabolic networks in ferroptosis.

Ferroptosis is an iron-dependent and peroxidation-driven form of cell death associated with multiple metabolic disorders and disrupted homeostasis. A number of metabolic processes and homeostasis are affected by ferroptosis. The molecules that regulate ferroptosis are involved in metabolic pathways that regulate cysteine exploitation, glutathione state, nicotinamide adenine dinucleotide phosphate function, lipid peroxidation and iron homeostasis. The present review summarizes the metabolic networks involved in ferroptosis based on previous studies, and discusses the function of ferroptosis in pathological processes, including cancer. Finally, the clinical significance of ferroptosis is highlighted, to provide evidence for further studies.

Polymer Self-Assembled BMSCs with Cancer Tropism and Programmed Homing.

Targeted therapy can improve the accuracy of diagnosis and treatment in the field of cancer management. Cellular surface engineering can enhance cell functions via mounting functional molecules onto cellular membranes. A novel amphiphilic hyperbranched polymer (AHP) conjugated with oleic acid (OA) and tumor-targeted ligand folic acid (FA) is employed. The lipophilic chain can self-assemble and infuse with the cytomembrane of bone marrow mesenchymal stem cells (BMSCs) with the end of FA left on the outside for targeting. The polymer tailored BMSCs can enhance tumor tropism in gastric cancer. BMSCs are characterized by the low immunogenicity and tumor tropism, which makes them promising targeting carriers. Regarding the integrated advantages of these two vectors, it is demonstrated that the functional amphiphilic AHP-OA-FA enhances the tumor tropism of BMSCs. Flow cytometry, standard MTT assay, and wound-healing assay show that AHP-OA-FA has no influence on CD expression, proliferative capacity, and cell motility of BMSCs, respectively. Furthermore, in vitro transwell assay and ex vivo fluorescence image verify that AHP-OA-FA enhances tumor tropism of BMSCs compared to BMSCs and AHP-OA-Rhodamine B-BMSCs. Finally, histological analysis demonstrates that AHP-OA-FA causes no damage to major organs. The results of this study suggest that living BMSCs self-assembled with a polymer might be a promising vehicle for targeted delivery to cancer cells.

Cysteine Dioxygenase 1 Mediates Erastin-Induced Ferroptosis in Human Gastric Cancer Cells.

BACKGROUND: Ferroptosis is a recently discovered form of iron-dependent nonapoptotic cell death. It is characterized by loss of the activity of the lipid repair enzyme, glutathione peroxidase 4 (GPX4), and accumulation of lethal reactive lipid oxygen species. However, we still know relatively little about ferroptosis and its molecular mechanism in gastric cancer (GC) cells. Here, we demonstrate that erastin, a classic inducer of ferroptosis, induces this form of cell death in GC cells and that cysteine dioxygenase 1 (CDO1) plays an important role in this process. METHODS: We performed quantitative real-time polymerase chain reaction, Western blotting, cell viability assay, reactive oxygen species (ROS) assay, glutathione assay, lipid peroxidation assay, RNAi and gene transfection, immunofluorescent staining, dual-luciferase reporter assay, transmission electron microscopy, and chromatin immunoprecipitation assay to study the regulation of ferroptosis in GC cells. Mouse xenograft assay was used to figure out the mechanism in vivo. RESULTS: Silencing CDO1 inhibited erastin-induced ferroptosis in GC cells both in vitro and in vivo. Suppression of CDO1 restored cellular GSH levels, prevented ROS generation, and reduced malondialdehyde, one of the end products of lipid peroxidation. In addition, silencing COO1 maintained mitochondrial morphologic stability in erastin-treated cells. Mechanistically, c-Myb transcriptionally regulated CDO1, and inhibition of CDO1 expression upregulated GPX4 expression. CONCLUSIONS: Our findings give a better understanding of ferroptosis and its molecular mechanism in GC cells, gaining insight into ferroptosis-mediated cancer treatment.