Eupalinolide B suppresses pancreatic cancer by ROS generation and potential cuproptosis.

Pancreatic cancer is highly lethal with limited effective treatments. This study explores the therapeutic effects of eupalinolide B (EB) from Eupatorium lindleyanum DC on pancreatic cancer cells. Through cellular functional assays, we observed that EB effectively inhibits cell viability, proliferation, migration, and invasion. In a xenograft mouse model, EB treatment resulted in reduced pancreatic cancer tumor growth and decreased expression of Ki-67. Mechanistically, EB induces apoptosis, elevates reactive oxygen species (ROS) levels, and disrupts copper homeostasis. RNA sequencing (RNA-seq) and gene set enrichment analysis (GSEA) identified copper ion binding pathways and potential involvement in cuproptosis. Furthermore, EB enhances the cytotoxic effects of elesclomol (ES), increasing ROS levels in a copper-dependent manner and exhibiting synergistic cytotoxicity. These findings suggest that EB, either alone or in combination with ES, represents a promising strategy for targeting metal ion dysregulation and inducing potential cuproptosis in pancreatic cancer, offering a potential improvement in therapeutic outcomes.

Risk Factors of Sarcopenia in COPD Patients: A Meta-Analysis.

Objective: Sarcopenia is a common complication of COPD associated with an age-related reduction in skeletal muscle mass associated with decreased muscle strength and / or reduced mobility. The incidence of sarcopenia in patients with COPD is twice that of non-COPD patients and is associated with poor prognosis, this study aimed to investigate the influencing factors of sarcopenia in COPD patients. Methods: Selected studies from PubMed, Embase, Web of Science, Cochrane Library, Wanfang, Wanfang, CNKI, CBM, and Wanfang databases as of November 12023. Patients aged 18 were selected; data were then independently extracted by two reviewers using a standard data collection form. Results: In total, 17 articles reporting on 5408 patients were included. Age (OR = 1.083; 95% CI, 1.024-1.145), ALB (OR = 0.752; 95% CI, 0.724-0.780), BMI(OR = 0.701; 95% CI, 0.586-0.838), smoking (OR = 1.859; 95% CI, 1.037-3.334), diabetes (OR = 1.361; 95% CI, 1.095-1.692), qi deficiency (OR = 9.883; 95% CI, 2.052, 47.593), GOLD C (OR =2.232; 95% CI, 1.866, 2.670) and GOLD D (OR = 2.195; 95% CI, 1.826-2.637) were factors affecting muscle loss in COPD patients. Conclusion: Sarcopenia is more prevalent in patients with COPD. Age, body mass index, smoking, diabetes mellitus, qi deficiency, ALB, and GOLD grade were the contributing factors for sarcopenia in patients with chronic obstructive pulmonary disease. In the future, medical staff should not only pay attention to the early screening of sarcopenia in high-risk groups, but also provide relevant prevention information.

Vulnerable Carotid Plaque is Associated with an Increased Risk of Intracerebral Hemorrhage in Individuals at High Risk of Stroke: A Chinese Population-based Cohort Study.

OBJECTIVES: To assess the association between carotid artery plaques and the risk of incident intracerebral hemorrhage (ICH) event in high-risk individuals for stroke. METHODS: We conducted a population-based cohort study using the longitudinal participant-level data of a multicenter, cross-sectional survey in southwestern China. 2644 high-risk participants for stroke were enrolled in the year 2015. The primary outcome was new-onset ICH events during a five-year follow-up period. Multivariate logistic regression was performed to identify the association between carotid plaque and new-onset ICH. Stratified analyses and interaction tests were conducted to identify variables that might modify the association between vulnerable carotid plaque and ICH. RESULTS: Among 2644 high-risk individuals enrolled, carotid plaques were found in 904 (34.2%) subjects, including 479 (18.1%) with stable plaques and 425 (16.1%) with vulnerable plaques. During a five-year follow-up period, 22 (0.83%) participants developed ICH. Vulnerable carotid plaque was associated with an increased risk of new-onset ICH in multivariable analyses (adjusted RR 3.72, 95 % CI 1.32 to 10.46, p=0.013). Stratified analyses and interaction analyses demonstrated the association between vulnerable carotid plaque and ICH was not changed by age, family history of stroke, hemorrhagic stroke and chronic disease, smoking, drinking, physical activity, BMI, antihypertensives, and antithrombotic drugs (all p for interaction>0.05). However, among the female cohort, participants with vulnerable plaques had a significantly higher risk of ICH compared with participants without vulnerable plaques (crude RR=9.8; 95%CI: 3.1-31.3, p<0.001; adjusted RR=26.3, 95%CI: 5.5-124.5, p<0.001), but not in man (p>0.05). CONCLUSION: In Chinese individuals at high risk of stroke, vulnerable carotid artery plaques are associated with an increased risk of intracerebral hemorrhage independent of classical vascular risk factors, especially in female individuals.

Relationship between health information literacy and health promoting lifestyle among first-degree relatives of patients with colorectal cancer in China: the mediating effect of health belief.

Background: History of first-degree relatives with colorectal cancer is one of the most important and common risk factors for colorectal cancer in China. Most chronic diseases, such as malignancies, are preventable by adopting health-promoting behaviors and other approaches. However, the relationships among factors affecting the health-promoting lifestyles of first-degree relatives with colorectal cancer have not been sufficiently studied. This study aimed to test the mediation effects of Health belief in the relationship between health-promoting lifestyle and health information literacy among first-degree relatives with colorectal cancer. Methods: A cross-sectional descriptive design was conducted using convenience sampling of 856 first-degree relatives of CRC patients attending three tertiary care hospitals in Nanchong and Deyang of China from December 2020 to December 2022. Questionnaires were used to collect data on the participants' demographic information, the colorectal cancer health beliefs, the health promotion lifestyle, and the health information literacy. Data were analyzed with descriptive statistics, one-way ANOVA, Pearson's correlation coefficients, and mediation analysis using SPSS 25.0 program and its macro-program PROCESS. Results: The findings indicated health information literacy was less, health belief was at the medium level, and performance of health promotion behavior was average for first-degree relatives of colorectal cancer. Whereas first-degree relatives of colorectal cancer health-promotion lifestyle had a positive correlation with health beliefs (r = 0.376, p < 0.01) and health information literacy (r = 0.533, p < 0.01), health beliefs had a positive correlation with health information literacy (r = 0.337, p < 0.01). Health beliefs mediated the positive effect of health information literacy on health-promoting lifestyles (ß =0.420, 95% CI, 0.288-0.581), and indirect effects accounted for 14.0% of the total effect. Conclusion: Health information literacy and health beliefs are key factors associated with a health-promoting lifestyle among first-degree relatives with colorectal cancer. These factors have direct and indirect effects on each other and on health-promoting lifestyles. To enhance health-promoting lifestyles among first-degree relatives with colorectal cancer, interventions that strengthen health beliefs and provide health information literacy should be developed.

Targeting epithelial cell-derived TWIST1 alleviates allergic asthma.

It is well known that the T Helper (Th)2 bias plays a critical role in allergic asthma. Whereas the Th2 bias is maintained in the local tissues is uncertain. IL-33 is vital for the development of the Th2 polarization. TWIST-1 has an effect on regulating cellular functions. The aberrant activation of RAS sustains certain cellular activities. The aim of this study is to study the role of the interaction between activation of TWIST1 and RAS in inducing and maintaining Th2 polarization in allergic asthma. The epithelial cells of the airways (AEC) were isolated from the broncho-alveolar lavage fluids in patients with asthma. The mediators involved in the over-expression of IL-33 were determined by RNA sequencing. A mouse model was established to test the role of TWIST1 and RAS in developing allergic asthma. We observed a strong expression of TWIST1 in patients with allergic asthma that showed a positive correlation with asthmatic responses. TWIST1 favored the expression of the IL-33 in the AEC. Twist1-deficient AEC-carrying mice did not induce Th2 polarization in the airways. The expression TWIST1 in AECs was positively associated with RAS activation in AECs in patients with allergic asthma. The interaction between RAS and TWIST1 in AECs sustained airway allergic inflammation. Inhibition of TWIST1 or RAS prevented asthma-like inflammation in the mouse airways. In summary, the interaction between TWIST1 and RAS induces and maintains IL-33 expression in AECs to facilitate allergic inflammation in the respiratory tract. Inhibition of TWIST1 or RAS can prevent experimental allergic asthma.

Iron-bound organic carbon dynamics in peatland profiles: The preservation equivalence of deep and surface soil.

More than half of the carbon pools in peatlands are stored in the soil layers below 30 cm, yet little is known about the carbon stabilizing factors at these depths. Although iron oxide minerals are considered to be important for stabilizing organic carbon (OC), their role in the preservation of OC in peatlands, especially in the deep layers, is poorly understood. Here, we collected 1 m soil profiles from six peatlands in Central and West China to quantitatively study the vertical distribution characteristics of iron-bound OC (Fe-bound OC), and the influencing physicochemical properties of the soil. The results showed that the content of reactive iron (FeR) was enriched in the top layer and decreased gradually with depth. While Fe-bound OC was positively correlated with FeR, its concentration did not decrease with depth in the peat profile. There were no obvious trends in the distributions of FeR and Fe-bound OC with water level fluctuations in the peat profile. In addition, the proportion of Fe-bound OC to soil organic carbon in the deep peat (31 to 100 cm) was equivalent to that in the surface peat (0 to 30 cm), indicating that iron oxide mineral provides comparable protection of OC in both layers. According to upper estimates of global peatland carbon storage (612 Pg), it could be predicted that 23.81 ± 11.75 Pg of OC is protected by association with FeR. These results indicated that iron oxide minerals are the effective "rusty sink" of OC sequestration in peatland, and a key factor for its long-term preservation. The results from this study make a valuable contribution to the carbon dynamics knowledgebase for peatlands, and provide a basis for improved predictive simulations.

CircKIF5B Promotes Hepatocellular Carcinoma Progression by Regulating the miR-192 Family/XIAP Axis.

Background: The long-term prognosis of HCC (hepatocellular carcinoma) with metastasis remains extremely poor. CircRNAs are promising as critical biological markers in identifying disease mechanisms and developing new effective treatments. However, the role of the aberrant expression of circRNAs in HCC progression remains largely unknown. Methods: CircKIF5B location was investigated by RNA fluorescence in situ hybridization (RNA-FISH). For circRNA determination, RNase R treatment and Real-Time Quantitative RT-PCR (qRT-PCR) were performed. Transwell chamber assays examined the chemotactic migration and invasion of liver cancer cells. Results: This study identified the circRNA circKIF5B originating from exons 1, 2, and 3 of the KIF5B gene. Importantly, we found that circKIF5B circRNA, rather than KIF5B linear mRNA, was notably upregulated in liver cancer cell lines and tissues. Moreover, we found that silencing circKIF5B markedly reduced the proliferation, invasion, and metastasis of liver cancer cells by sponging the miR-192 family, thus decreasing the expression of X-linked inhibitor of apoptosis (XIAP). Conclusion: Our data demonstrate that circKIF5B can regulate XIAP expression by sponging miR-192 and miR-215 competing for the ceRNA mechanism, indicating that circKIF5B may act as an essential upstream regulator and providing mechanistic evidence to support the view that circKIF5B/miR-192s/XIAP is a promising therapeutic target for treating liver cancer.

Prevalence and Risk Factors of High-Risk Population for Stroke: A Population-Based Cross-Sectional Survey in Southwestern China.

With the aging of the population and the change of lifestyle in China, the prevalence and risk factors of the high-risk population for stroke may change. However, few studies performed community-based high-risk stroke population surveys in China. Hence, we performed this multicenter, cross-sectional, and community-based survey in Sichuan of southwestern China, according to the China National Stroke Screening Survey (CNSSS) program in 2015. The residents aged ≥ 40 years volunteered to participate in the face-to-face survey in 8 communities in Sichuan. The 8 communities were selected using the cluster randomization method. Subjects with at least three of the eight stroke-related risk factors were classified as a high-risk population for stroke. Otherwise were classified as a low-risk population for stroke. Furthermore, 1,011 individuals were randomly selected among the low-risk population for stroke as controls. Among 16,892 participants, 2,369 (14.0%) were high-risk population for stroke. After full adjustments, all eight risk factors for stroke were significantly associated with the high-risk population for stroke (P < 0.001). The largest contributor was hypertension [population-attributable risk (PAR) 28.4%], followed by physical inactivity (PAR 14.2%), dyslipidemia (PAR 11.2%), overweight/obesity (PAR 9.4%), diabetes (PAR 7.2%), family history (PAR 6.8%), smoking (PAR 5.9%), and atrial fibrillation (PAR 3.5%). Carotid atherosclerosis was more serious in the high-risk population for stroke than in controls (P < 0.05). The prevalence of the high-risk population for stroke was high in southwestern China. Hypertension, physical inactivity, and dyslipidemia were stronger contributors for the high-risk population for stroke. Individual-level and population-level interventions for these leading risk factors are very important for the primary prevention of stroke.

Efficacy of Intravitreal Injection of Filtered Modified Low-Dose Triamcinolone Acetonide and Ranibizumab on Pseudophakic Cystoid Macular Edema.

PURPOSE: To compare the visual and morphological effects between intravitreal injection of filtered modified 2 mg triamcinolone acetonide (TA) and 0. 5 mg ranibizumab in patients with pseudophakic cystoid macular edema (PCME). METHODS: A retrospective, interventional study was conducted from January 2015 to February 2020 involving patients with PCME after uneventful cataract surgery. A total of 25 patients (25 eyes) with PCME received an intravitreal injection of 0.22 µm filtered modified 2 mg TA, while 15 patients (15 eyes) received 0.5 mg ranibizumab injection. Central macular thickness (CMT), best-corrected visual acuity (BCVA), intraocular pressure (IOP), times of repeated injections, and other side effects were observed at 2 weeks, 1 month, 3 months, and 6 months after injection; then, the data were compared with preinjection information in each group and between the two groups. RESULTS: Both the TA and ranibizumab intravitreal injection can achieve improved BCVA and reduced CMT in patients with PCME (P < 0.05), with a trend toward greater improvement in the TA group, but the difference was only significant at 3 months (P < 0.05). IOP was in the normal range without any significant difference (P > 0.05). Thirty-three percent of patients in the ranibizumab group required repeated intravitreal injection compared to 4% in the TA group. Further stratified analysis showed that the better therapeutic effect of the TA group at 3 months after injection only existed in patients with diabetes mellitus (DM), while not in patients without DM. There was no repeat injection in the TA group and 12.5% in the ranibizumab group for patients without DM, while 16.7% in the TA group and 57.1% in the ranibizumab group required repeated injection for patients with DM, which had a significant difference (P < 0.05). CONCLUSION: Intravitreal injection of filtered modified 2 mg TA is safe, effective, and an inexpensive alternative to antivascular endothelial growth factor (anti-VEGF) agents for patients with PCME, especially for patients concurrently with DM. A large number of clinical randomized controlled studies along with long-term follow-up observations are needed.

Safety and effectiveness of an iris hook assisted phacoemulsification in vitrectomized eyes.

AIM: To introduce a simple iris hook assisted phacoemulsification (PE) procedure and evaluate the safety and efficacy of it in completely vitrectomized eyes. METHODS: A single centre study which included 65 previously completely vitrectomized eyes of 62 patients who underwent cataract surgery. Patients were randomly divided into 3 groups. Patients received PE, and intraocular lens (IOL) implantation with the assistance of iris hook (Synergeties™) as group A (25 eyes); patients who received PE assisted with a 25G pars plana irrigation as group B (20 eyes), and patients who received PE performed without the help of any instrument as group C (20 eyes). Main outcome measures were surgery duration, Ultrasound (U/S) total time, endothelial cell density (ECD), cumulative dissipated energy (CDE) and complications of the procedures. RESULTS: With the help of iris hook, the patients in group A had the lowest ECD loss rate (0.07±0.03, 0.09±0.03, and 0.10±0.03, P<0.05), shortest CDE (12.2±4.1, 15.8±6.0, and 16.0±6.0, P<0.05) and U/S total time (36.6±13.0s, 46.3±16.4s, and 47.6±16.1s, P<0.05), and minimal incidence of complications. The longest surgery duration was in group B (19.4±1.6min) and maximum complications rate in group C (20% miosis, 10% posterior capsular tears, 5% zonular dialysis, 5% cystoid macular edema). While best-corrected visual acuity (BCVA), intraocular pressure (IOP) and ECD did not show a significant difference among the three groups. CONCLUSION: Without prolonged surgery duration, the iris hook assistant method can minimize heat generation during surgery and incidence of complications, which transfer the challenged PE in vitrectomized eyes into a regular surgery. It does not need any change in the hydrodynamic parameters and in the bag PE technique, easy to operate even for junior surgeons.

Bioprospecting of rhamnolipids production and optimization by an oil-degrading Pseudomonas sp. S2WE isolated from freshwater lake.

The present study revealed biosurfactants production by a novel oil-degrading Pseudomonas sp. S2WE isolated from hydrocarbon enriched water sample, where the genus Pseudomonas (48.65%) was dominated amongst several other genera. Biosurfactants produced by this strain showed the great potential for surface tension reduction (SFT) and emulsification. The extracted crude biosurfactants were characterized using ultra-high-performance liquid chromatography-Mass Spectrometry (UHPLC-MS) and identified various mono-and di-rhamnolipids homologs from the mixture. Moreover, the lowest SFT 33.05 ± 0.1 mN/m and highest emulsification of 60.65 ± 0.64% were achieved from rhamnolipids produced from glycerol with urea. Compared to initial screening, almost (>87%) higher emulsification was observed. In addition, the biosurfactants were found highly stable at different environmental factors i.e. temperature (4 °C-121 °C), pH (3-10) and NaCl conc. (1-9%). The high stable rhamnolipids produced by new Pseudomonas sp. S2WE in this study could widely be used in enormous industrial as well as environmental applications.

The Optimization of an Anti-VEGF Therapeutic Regimen for Neovascular Glaucoma.

This study investigates the safety and efficacy of conbercept injection through different routes for neovascular glaucoma (NVG) treatment, in which seventy-four patients (81 eyes) with NVG caused by ischemia retinopathy had participated. Patients were divided into three stages according to the progression of NVG and were randomly assigned to receive intracameral or intravitreal conbercept injection. After conbercept injection, patients experienced improved best-corrected visual acuity (BCVA), good intraocular pressure (IOP) control, and neovascularization of Iris (NVI) regression. In stage III, patients required trabeculectomy with mitomycin C plus pan-retinal photocoagulation (PRP) to achieve complete NVI regression. Compared to the intravitreal group, the intracameral group had significantly lower IOP in 2 days in stage III and 1 day in stages I and II after injection, complete NVI regression before PRP in stages I and II, and better NVI regression in stage III. The rates of hyphema after trabeculectomy and malfunction filtering bleb suffering needle bleb revision were lower in the intracameral group, but only the hyphema rate was significantly different. Injections through different routes are all safe. We recommend intravitreal injections for patients in stages I and II, but for stage III, intracameral injection is better, and trabeculectomy with mitomycin C should be conducted within 2 days after injection to maximally reduce the risk of perioperative hyphema. Trial Registration: ClinicalTrials.gov, identifier NCT03154892.

A Preliminary Study of Predicting Effectiveness of Anti-VEGF Injection Using OCT Images Based on Deep Learning.

Deep learning based radiomics have made great progress such as CNN based diagnosis and U-Net based segmentation. However, the prediction of drug effectiveness based on deep learning has fewer studies. Choroidal neovascularization (CNV) and cystoid macular edema (CME) are the diseases often leading to a sudden onset but progressive decline in central vision. And the curative treatment using anti-vascular endothelial growth factor (anti-VEGF) may not be effective for some patients. Therefore, the prediction of the effectiveness of anti-VEGF for patients is important. With the development of Convolutional Neural Networks (CNNs) coupled with transfer learning, medical image classifications have achieved great success. We used a method based on transfer learning to automatically predict the effectiveness of anti-VEGF by Optical Coherence tomography (OCT) images before giving medication. The method consists of image preprocessing, data augmentation and CNN-based transfer learning, the prediction AUC can be over 0.8. We also made a comparison study of using lesion region images and full OCT images on this task. Experiments shows that using the full OCT images can obtain better performance. Different deep neural networks such as AlexNet, VGG-16, GooLeNet and ResNet-50 were compared, and the modified ResNet-50 is more suitable for predicting the effectiveness of anti-VEGF.Clinical Relevance - This prediction model can give an estimation of whether anti-VEGF is effective for patients with CNV or CME, which can help ophthalmologists make treatment plan.

Production and characterization of surfactin-like biosurfactant produced by novel strain Bacillus nealsonii S2MT and it's potential for oil contaminated soil remediation.

BACKGROUND: Biosurfactants, being highly biodegradable, ecofriendly and multifunctional compounds have wide applications in various industrial sectors including environmental bioremediation. Surfactin, a member of lipopeptide family, which is considered as one of the most powerful biosurfactants due to its excellent emulsifying activities as well as environmental and therapeutic applications. Therefore, the aim of this study was to investigate the newly isolated bacterial strain S2MT for production of surfactin-like biosurfactants and their potential applications for oil-contaminated soil remediation. RESULTS: In this study, the strain S2MT was isolated from lake sediment and was identified as Bacillus nealsonii based on transmitted electron microscopy (TEM) and 16S rRNA ribo-typing. The strain S2MT produced biosurfactant that reduced the surface tension (34.15 ± 0.6 mN/m) and displayed excellent emulsifying potential for kerosene (55 ± 0.3%). Additionally, the maximum biosurfactant product yield of 1300 mg/L was achieved when the composition of the culture medium was optimized through response surface methodology (RSM). Results showed that 2% glycerol and 0.1% NH4NO3 were the best carbon/nitrogen substrates for biosurfactant production. The parameters such as temperature (30 °C), pH (8), agitation (100 rpm), NH4NO3 (0.1%) and NaCl (0.5%) displayed most significant contribution towards surface tension reduction that resulted in enhanced biosurfactant yield. Moreover, the extracted biosurfactants were found to be highly stable at environmental factors such as salinity, pH and temperature variations. The biosurfactants were characterized as cyclic lipopeptides relating to surfactin-like isoforms (C13-C15) using thin-layer chromatography (TLC), Ultra high performance liquid chromatography and mass spectrometry (UHPLC-MS). The crude biosurfactant product displayed up to 43.6 ± 0.08% and 46.7 ± 0.01% remediation of heavy engine-oil contaminated soil at 10 and 40 mg/L concentrations, respectively. CONCLUSION: Present study expands the paradigm of surfactin-like biosurfactants produced by novel isolate Bacillus nealsonii S2MT for achieving efficient and environmentally acceptable soil remediation as compared to synthetic surfactants.

A Pilot Study of Parameter-Optimized Low-Intensity Pulsed Ultrasound Stimulation for the Bone Marrow Mesenchymal Stem Cells Viability Improvement.

To investigate how a back propagation neural network based on genetic algorithm (GA-BPNN) optimizes the low-intensity pulsed ultrasound (LIPUS) stimulation parameters to improve the bone marrow mesenchymal stem cells (BMSCs) viability further. The LIPUS parameters were set at various frequencies (0.6, 0.8, 1.0, and 1.2 MHz), voltages (5, 6, 7, and 8 V), and stimulation durations (3, 6, and 9 minutes). As only some discrete points can be set up in the experiments, the optimal LIPUS stimulation parameter may not be in the value of these settings. The GA-BPNN algorithm is used to optimize parameters of LIPUS to increase the BMSCs viability further. The BMSCs viability of the LIPUS-treated group was improved up to 19.57% (P < 0.01). With the optimization via the GA-BPNN algorithm, the viability of BMSCs was further improved by about 5.36% (P < 0.01) under the optimized condition of 6.92 V, 1.02 MHz, and 7.3 min. LIPUS is able to improve the BMSCs viability, which can be improved further by LIPUS with parameter optimization via GA-BPNN algorithm.

CircRNAs in cancer metabolism: a review.

Altered energy metabolism is a hallmark of tumors aiming at supplying necessary nutrients for tumorigenesis and development. These redirected metabolic pathways associated with carbohydrate, lipid and amino acid are orchestrated not only by carcinogenic proteins but by non-coding RNAs. Among them, circular RNA (circRNA), as a kind of novel identified non-coding RNAs, has become the focus of attention. Through binding with corresponding microRNAs or directly contacting proteins, circRNA plays a primarily important role in regulating cellular metabolism. Herein, we analyze the emerging findings and select circRNAs contributing to mutant glycolysis, lipogenesis and lipolysis, glutam inolysis, and oxidative respiration to deepen the understanding about the cancer metabolic regulatory network. In addition, we also discuss the possibility of circRNAs exerting their functions via exosomes and cancer stem cells. Owing to their unique structures and wide impacts, circRNAs may help reap huge fruits in developing clinical treatments targeting cancer metabolism.

Stroke-related complications in large hemisphere infarction: incidence and influence on unfavorable outcome.

OBJECTIVE: Neurological and medical complications are major causes of morbidity and mortality after ischemic stroke. This study aimed to identify the incidence of stroke-related complications following large hemisphere infarction (LHI) and to explore their influence on unfavorable outcome in LHI patients. METHODS: We prospectively enrolled consecutive patients with LHI. The unfavorable outcome was defined as an modified Rankin Scale (mRS) score of 4-6 at 3 months. Multivariate logistic regression analysis was employed to identify the stroke-related complications associated with unfavorable outcome. RESULTS: Of the 256 cases with LHI included, 41 (16.0%) died during hospitalization, 94 (36.7%) died and 140 (55.3%) patients had unfavorable outcome at 3 months. A total of 194 (75.8%) had at least one complication. The three most common medical complications were pneumonia (53.5%), electrolyte disorder (30.9%), and urinary incontinence (18.4%), and the three most common neurological complications were malignant brain edema (31.2%), hemorrhagic transformation (27.7%), and poststroke seizures (7.0%). Overall, LHI patients with unfavorable outcome had more frequent stroke-related complications (91.4% versus 55.8%, p < 0.001) than patients with favorable outcome. After adjusting for age, baseline National Institutes of Health Stroke Scale score, and other confounders, only malignant brain edema [odds ratios (OR) 19.76, 95% confidence interval (CI) 4.73-82.45] and pneumonia (OR 2.45, 95% CI 1.11-5.40) were independently associated with 3-month unfavorable outcome in patients with LHI. CONCLUSIONS: More than three-quarters of LHI patients have at least one stroke-related complication. LHI patients with the unfavorable outcome had stroke-related complications more frequently, whereas only malignant brain edema and pneumonia are independently associated with 3-month unfavorable outcome.

KLF5 and MYC modulated LINC00346 contributes to gastric cancer progression through acting as a competing endogeous RNA and indicates poor outcome.

It was found in this study that long intergenic non-protein coding RNA 346 (LINC00346) was an lncRNA aberrantly expressed in gastric cancer (GC) based on multiple Gene Expression Omnibus (GEO) databases of GC cohorts. The LINC00346 gene was recurrently amplified and upregulated in GC, and its expression was positively correlated with poor pathologic stage, large tumor size, and poor prognosis. In addition, the oncogenic transcription factors KLF5 and MYC could bind to the LINC00346 promoter and enhance its expression. Gene Set Enrichment Analysis (GSEA) in the GEO datasets revealed that cell cycle and focal adhesion genes were enriched in patients with high LINC00346 expression. In vitro and in vivo assays of LINC00346 alterations revealed a complex integrated phenotype affecting cell growth, migration and invasion. Strikingly, high-throughput sequencing analysis after LINC00346 alterations highlighted alterations in cell cycle and focal adhesion pathways in GC cells. Mechanistically, argonaute 2 (Ago2) was recruited by LINC00346, which functioned as a molecular sponge for miR-34a-5p by antagonizing its ability to repress CD44, NOTCH1, and AXL protein translation. Taken together, our findings support a model in which the KLF5, MYC/LINC00346/miR-34a-5p cross-talk served as critical effectors in GC tumorigenesis and progression, suggesting a new therapeutic direction in the treatment of GC.

EZH2-mediated epigenetic suppression of EphB3 inhibits gastric cancer proliferation and metastasis by affecting E-cadherin and vimentin expression.

EphB3 is a member of the EPH family of receptors and has been found to play a role in the carcinogenesis of some human cancers. However, its expression and clinical significance in gastric cancer (GC) have not been well documented. In the present study, we detected the expression of EphB3 in GC and adjacent noncancerous tissues and explored its relationships with the clinicopathological features and prognosis of GC patients. It was found that EphB3 silenced GC cells epigenetically by direct transcriptional repression of GC cells via polycomb group protein EZH2 mediation. EphB3 was downregulated in GC cells and tissues, and EphB3 depletion promoted GC cell growth and invasion, while ectopic overexpression of EphB3 produced a significant anti-tumor effect. EphB3 was found to be involved in epithelial-mesenchymal transition by regulating E-cadherin and vimentin expression. In addition, patients with reduced EphB3 expression had shorter disease-free survival (DFS), indicating that EphB3 may prove to be a biomarker for prognosis of GC. These results demonstrated that EphB3 functioned as a tumor-suppressor and prognostic biomarker in GC.

Silencing of cadherin-17 enhances apoptosis and inhibits autophagy in colorectal cancer cells.

Cadherin-17 (CDH17), a structurally unique member of the non-classical cadherin family, is associated with poor survival, cell proliferation, and metastasis in colorectal cancer. However, the role of CDH17 in the apoptosis and autophagy of colorectal cancer cells remains unclear. Here, we aimed to investigate the effect of CDH17 knockdown on autophagy and apoptosis in colorectal cancer cells. We inhibited CDH17 expression in KM12SM and KM12C colorectal cancer cells by RNA interference and found that silencing of CDH17 significantly inhibited cell viability and increased apoptosis in KM12SM and KM12C cells. In addition, silencing of CDH17 significantly increased the expression of cleaved caspase-3 and Bax and decreased the expression of Bcl-2. Concurrently, silencing of CDH17 significantly inhibited the conversion of LC3-I to LC3-II and decreased the formation of LC3+ autophagic vacuoles and the accumulation of acidic vesicular organelles, indicating that autophagy was significantly inhibited in KM12SM and KM12C cells. Additionally, treatment with the autophagy-specific activator rapamycin attenuated apoptosis in CDH17-knockdown cells and as indicated by decreased caspase-3 activity, decreased expression of cleaved caspase-3 and Bax, and increased expression of Bcl-2. In conclusion, CDH17 silencing induced apoptosis and inhibited autophagy in KM12SM and KM12C cells, and this autophagy protected the cells from apoptotic cell death.