Integrative approach for efficient detection of kidney stones based on improved deep neural network architecture.

In today's digital world, with growing population and increasing pollution, unhealthy lifestyle habits like irregular eating, junk food consumption, and lack of exercise are becoming more common, leading to various health problems, including kidney issues. These factors directly affect human kidney health. To address this, we require early detection techniques that rely on text data. Text data contains detailed information about a patient's medical history, symptoms, test results, and treatment plans, giving a complete picture of kidney health and enabling timely intervention. In this research paper, we proposed a range of sophisticated models, such as Gradient Boosting Classifier, Light GBM, CatBoost, Support Vector Classifier (SVC), Random Boost, Logistic Regression, XGBoost, Deep Neural Network (DNN), and an Improved DNN. The Improved DNN demonstrated exceptional performance, with an accuracy of 90 %, precision of 89 %, recall of 90 %, and an F1-Score of 89.5 %. By combining traditional machine learning and deep neural networks, this integrative approach enables the identification of intricate patterns in datasets. The model's data-driven processes consistently update internal parameters, guaranteeing flexibility in response to evolving healthcare settings. This research represents a notable advancement in the progress of creating a more detailed and individualised ability to diagnose kidney stones, which could potentially lead to better clinical results and patient treatment.

A novel dual polarization multiplexing RoF system integrating optical fiber and FSO channel with AMI downlink signals.

Using dual polarization multiplexing alternate mark inversion (AMI) downlink signals, a novel radio over fiber (RoF) system integrating optical fiber and FSO channel is designed to adapt to applications in mountainous areas and other complex terrain areas. Optical heterodyne technology and self-mixing homodyne detection method are used to realize high sensitivity detection of the received signals after 25.1 km channel (including 1 km single-mode fiber and 100 m free space link) transmission. Moreover, polarization multiplexing technology is introduced to exponentially increase the transmission capacity of downlink signals. This scheme not only can be compatible with traditional optical fiber transmission systems, but also support the wireless optical access application of millimeter wave signals in RoF systems.

Celastrus orbiculatus extract reverses precancerous lesions of gastric cancer by inhibiting autophagy via regulating the PDCD4-ATG5 signaling pathway.

OBJECTIVES: Celastrus orbiculatus ethyl acetate extract (COE) is the main extract of the stem of the Chinese herbal C. orbiculatus, which has anti-tumor and anti-inflammatory biological effects. Our previous study showed that COE had a certain reversal effect on the precancerous lesions of gastric cancer (PLGC) in rats, but the exact mechanism of action remains elusive. We aimed to explore the therapeutic effects of COE on PLGC and the potential mechanisms. METHODS: The PLGC rat model was successfully constructed by N-methyl-N´-nitro-N-nitrosoguanidine (MNNG) multifactorial induction method. Then, COE was prepared to treat the PLGC rat model. Hematoxylin & eosin staining was used to observe gastric mucosal lesions in rats, AB-PAS and HID-AB staining were used to observe intestinal metaplasia. PDCD4-ATG5 signaling pathway was detected by immunohistochemistry (IHC) and reverse transcription polymerase chain reaction (RT-PCR) in vivo, and autophagy level was detected by IHC, transmission electron microscopy, and RT-PCR in vivo. Besides, the PLGC (MC) cell model was successfully constructed by treating GES-1 cells with MNNG. Then, the morphology, proliferation, and apoptosis of MC cells, and the role of the PDCD4-ATG5 signaling pathway and autophagy in MC cells were evaluated by COE and after the overexpression of PDCD4 treatment. KEY FINDINGS: COE significantly improved gastric mucosal injury and cellular heteromorphism and retarded the progression of PLGC in rats. Further studies indicated COE not only inhibited the level of autophagy but also interfered with the PDCD4-ATG5 signaling pathway in vivo. On the other hand, COE treatment could effectively reverse MC cell damage, inhibit MC cell proliferation, and promote MC cell apoptosis. Furthermore, COE also promoted PDCD4 and inhibited ATG5 expression in vitro, and the inhibitory effect of COE on ATG5-mediated autophagy was further enhanced after the overexpression of PDCD4. CONCLUSIONS: The study revealed that COE could regulate the PDCD4-ATG5 signaling pathway to inhibit autophagy in gastric epithelial cells, which contributes to reversing the progression of PLGC.

Effect of Helicobacter pylori eradication on gastric precancerous lesions: A systematic review and meta-analysis.

BACKGROUND: The question of whether eradication of Helicobacter pylori (Hp) can reverse gastric precancerous lesions, including intestinal metaplasia, remains uncertain, leading to ongoing debate. Therefore, a meta-analysis was performed to evaluate the effect of Hp eradication on gastric precancerous lesions. MATERIALS AND METHODS: PubMed, Embase, Cochrane Library, Web of Science, Scopus database, and ClinicalTrials.gov were systematically searched from inception to April 2023 for studies that explored the impact of Hp eradication on gastric precancerous lesions. Risk ratios (RRs) and their 95% confidence intervals (95% CIs) were selected as the effect size. We used the random-effects model to assess pooled data. We also performed quality assessments, subgroup analyses, and sensitivity analyses. RESULTS: Fifteen studies were included. Compared with placebo, Hp eradication could significantly prevent the progression of gastric precancerous lesions (RR = 0.87, 95% CI: 0.81-0.94, p < 0.01) and reverse them (RR = 1.32, 95% CI: 1.17-1.50, p < 0.01). Then, specific precancerous lesions were further explored. The progression of intestinal metaplasia was significantly prevented by Hp eradication compared to placebo or no treatment (RR = 0.80, 95% CI: 0.69-0.94, p < 0.01). Moreover, compared with placebo or no treatment, Hp eradication also improved chronic atrophic gastritis (RR = 1.84, 95% CI: 1.30-2.61, p < 0.01) and intestinal metaplasia (RR = 1.41, 95% CI: 1.15-1.73, p < 0.01). However, in terms of preventing dysplasia progression (RR = 0.86, 95% CI: 0.37-2.00) and improving dysplasia (RR = 0.89, 95% CI: 0.47-1.70), Hp eradication had no advantage compared to placebo or no treatment. CONCLUSIONS: Hp eradication therapy could prevent the progression of gastric precancerous lesions and reverse them. Notably, intestinal metaplasia can be reversed, but this may only be appropriate for patients with epigenetic alterations and milder lesions.

Effectiveness and safety of mono-anlotinib mono therapy or in combination with chemotherapy in platinum-resistant recurrent ovarian cancer: a single-center retrospective study.

OBJECTIVE: To evaluate the clinical efficacy of mono-anlotinib therapy by itself or in combination with chemotherapy in platinum-resistant recurrent ovarian cancer (PROC). METHODS: The clinical data of 35 patients with platinum-resistant recurrent ovarian cancer admitted to the First Affiliated Hospital of Anhui Medical University from March 2019 to July 2020 were retrospectively analyzed. All the patients received anlotinib mono- or combined chemotherapy. The effectiveness and adverse events (AEs) were analyzed by RECIST1.1 and CTCAE5.0. RESULTS: In the 35 patients, the median follow-up was 9.80 (95% CI: 3.83-15.77) months. The median progression free survival (mPFS) achieved 6.50 (95% CI: 2.02-10.98) months, the objective response rate (ORR) achieved 17.14%, and disease control rate (DCR) achieved 60.00%. ORR and DCR were 12.50% and 25.0% for monotherapy, 18.52% and 70.37% for combined chemotherapy. The PFS of combined chemotherapy was longer than that of monotherapy (log-rank P = 0.003). thirty-four patients (97.14%) were in a third-line therapy or above, and their ORR and DCR were 14.71% and 58.82%, respectively. Two patients discontinued treatment because of intolerable AEs. No cases of grade 4-5 AEs have been reported. CONCLUSION: Anlotinib had promising effectiveness and tolerable safety in patients with PROC, even in patients who accepted anlotinib as a third-line or above therapy or with a history of other antiangiogenic drugs.

Comparison of efficacy and tolerability of adjuvant therapy for resected high-risk stage III-IV cutaneous melanoma: a systemic review and Bayesian network meta-analysis.

Background: Although immune checkpoint inhibitors (ICIs) and targeted therapies have been widely used as adjuvant treatment for resected melanoma, the optimal therapy remains controversial. Therefore, we conducted this updated network meta-analysis (NMA) to assess the efficacy and tolerability of adjuvant therapies for cutaneous melanoma. Methods: PubMed, Embase, Cochrane library, and Web of Science were systematically searched for relevant literatures published in the last 30 years. Disease-free survival (DFS), overall survival (OS), and serious adverse events were considered as the efficacy and tolerability outcomes. Results: In all, 27 randomized controlled trials (RCTs) including 16,709 stage III-IV melanoma patients were enrolled in this NMA. For BRAF wild-type melanoma, our analysis showed that both nivolumab and pembrolizumab demonstrated significantly better DFS and tolerability than ipilimumab (10 mg/kg). Nivolumab, pembrolizumab, ipilimumab (3 mg/kg), and ipilimumab (10 mg/kg) all appeared to be effective in prolonging OS, but no therapy demonstrated significantly better OS than ipilimumab (10 mg/kg). Nivolumab + ipilimumab showed the best DFS, but did not appear to be effective in improving OS and ranked only seventh in tolerability. Vaccines and granulocyte-macrophage colony-stimulating factor therapies were well tolerated, but all failed to improve the DFS or OS in stage III melanoma patients. In terms of BRAF mutation-positive melanoma, ICIs (nivolumab + ipilimumab, nivolumab, pembrolizumab, ipilimumab; 10 mg/kg) exhibited comparable efficacy to dabrafenib + trametinib, and all these therapies showed significantly better DFS than placebo. Conclusion: Considering efficacy and tolerability, nivolumab and pembrolizumab seem to be preferable adjuvant therapies for patients with stage III-IV melanoma. For BRAF mutation-positive patients, more RCTs are still required to determine which is better between ICIs and targeted therapy.

Helicobacter pylori infection and PD-L1 expression in gastric cancer: A meta-analysis.

BACKGROUND: High expression of programmed death ligand-1 (PD-L1) has been related to good response to immunotherapy patients with gastric cancer (GC). However, the influence of Helicobacter pylori (HP) infection on PD-L1 expression in GC remains unknown. A meta-analysis was performed to evaluate the association between HP infection and PD-L1 expression in GC. METHODS: Observational studies that investigated the relationship between HP infection and PD-L1 expression in patients with GC were obtained by search electronic databases, including PubMed, Embase, Cochrane's Library and Web of Science. A random-effect model incorporating the possible influence of between-study heterogeneity was used to pool the results. RESULTS: Ten studies with 1870 patients with GC contributed to the meta-analysis. Pooled results showed that HP infection was significantly associated with the tumour expression of PD-L1 (odds ratio [OR]: 1.90, 95% confidence interval: 1.33-2.72, p < .001; I2  = 53%). Subgroup analyses showed that the association between HP infection and PD-L1 expression in GC was not significantly affected by sample size, methods for PD-L1 evaluation and quality score (p for subgroup analyses all >.05). However, a stronger association was observed in studies with higher prevalence of HP infection (≥35%, OR: 2.58) as compared with those with lower prevalence (<35%, OR: 1.45, p for subgroup difference = .04). CONCLUSION: Helicobacter pylori infection in GC patients is associated with tumour expression of PD-L1, suggesting HP infection may be a predictor of good response to immunotherapy in GC.

The relationship between blood-based tumor mutation burden level and efficacy of PD-1/PD-L1 inhibitors in advanced non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: The predictive role of blood-based tumor mutation burden (bTMB) for selecting advanced nonsmall cell lung cancer (NSCLC) patients who might benefit from immune checkpoint inhibitors (ICIs) is still under debate. Therefore, the purpose of this meta-analysis was to evaluate the efficacy of programmed cell death 1 (PD-1) /programmed cell death ligand 1 (PD-L1) inhibitors versus that of standard-of-care therapy in patients with NSCLC who were bTMB high and bTMB low. METHODS: PubMed, Embase, Cochrane, the Web of Science, and ClinicalTrials.gov were searched systematically from inception to February 2021 for studies of PD-1/PD-L1 inhibitors (durvalumab OR atezolizumab OR avelumab OR pembrolizumab OR Nivolumab) that provided hazard ratios (HRs) for overall survival (OS) or progression-free survival (PFS), or odds ratios (ORs) for objective response rate (ORR) in both bTMB high and bTMB low groups. RESULTS: A total of 2338 patients with advanced or metastatic NSCLC from six randomized controlled trials, which all used chemotherapy (CT) as a control, were included in this study. Compared with CT, PD-1/PD-L1 inhibitor therapy improved OS (HR 0.62, 95% CI 0.52-0.75, P < 0.01), PFS (HR 0.57, 95% CI 0.48-0.67, P < 0.01), and ORR (OR 2.69, 95% CI 1.84-3.93, P < 0.01) in bTMB-high NSCLC patients but not in bTMB-low patients (OS HR 0.86, 95% CI 0.69-1.07, P = 0.17; PFS HR 1.00, 95% CI 0.78-1.27, P = 0.98; ORR OR 0.63, 95% CI 0.49-0.80, P = 0.03). Subgroup analyses showed that these results were consistent across all subgroups (line of therapy, therapy regimen, type of NGS panel, PD-L1 expression, and cutoff value). Meta-regression analysis showed that the proportion of patients with squamous cell histology had no statistical effect on clinical outcomes. Sensitivity analyses illustrated that all results were stable. CONCLUSIONS: The efficacy of PD-1/PD-L1 inhibitor therapy in advanced NSCLC patients may be dependent on bTMB level. Patients with high bTMB tend to obtain significantly better OS, PFS, and ORR from PD-1/PD-L1 inhibitor therapy than from CT. However, because of multiple limitations, including those related to reproducibility, the results are exploratory and should be interpreted with caution.

Celastrus orbiculatus Extract Reduces Stemness of Gastric Cancer Stem Cells by Targeting PDCD4 and EIF3H.

BACKGROUND: Celastrus orbiculatus ethyl acetate extract (COE) has shown a strong anti-gastric cancer effect, but the understanding of its mechanism is still lacking. The results of previous studies indicated that COE may be able to inhibit the stemness of gastric cancer stem cells (GCSCs) by regulating PDCD4 and EIF3H expression. AIMS: To explore if COE could inhibit the stemness of GCSCs by regulating PDCD4 and EIF3H expression in vitro and in vivo. PROCEDURE: The GCSCs model was established by stem cell-conditioned culture. Spheroid formation and flow cytometry assays were used to detect the effect of COE on the spheroid formation ability of GCSCs and the percentage of CD44+/CD24+ and ALDH+ cell subpopulations. Western blot analysis was applied to measure the expression of GCSCs biomarkers (Nanog, Oct-4, and SOX-2), PDCD4, and EIF3H in GCSCs treated with COE; and RT-PCR was performed to investigate the effect of COE on PDCD4 mRNA expression in GCSCs. An in vivo tumorigenicity experiment was also conducted to evaluate the effect of COE on tumor-initiating ability of GCSCs in vivo; and the expression of PDCD4 and EIF3H in xenograft tissues was examined by immunohistochemistry (IHC) staining. RESULTS: After culture in stem cell-conditioned medium, SGC7901 cells manifested significantly enhanced spheroid formation ability, upregulated Nanog, Oct-4, and SOX-2 expression and increased percentages of CD44+/CD24+ and ALDH+ cell subpopulations, indicating successful establishment of the GCSCs model. COE treatment significantly inhibited the spheroid formation ability of GCSCs and reduced the percentage of CD44+/CD24+ and ALDH+ cell subpopulations. The western blot analysis showed a significant decrease of Nanog, Oct-4, SOX-2, and EIF3H expression and an increase of PDCD4 expression in GCSCs after COE treatment in a concentration-dependent manner. COE treatment also significantly upregulated the mRNA expression of PDCD4 in GCSCs. In addition, COE displayed a strong inhibitory effect on the tumor-initiating ability of GCSCs in vivo and upregulated PDCD4 and downregulated EIF3H expression in xenograft tissues. CONCLUSION: COE may be able to inhibit GC growth by suppressing the stemness of GCSCs via regulating PDCD4 and EIF3H expression.

Long non-coding SBF2-AS1 acting as a competing endogenous RNA to sponge microRNA-142-3p to participate in gemcitabine resistance in pancreatic cancer via upregulating TWF1.

OBJECTIVE: This study is implemented to probe into the function of lncRNA SBF2-AS1 as a competing endogenous RNA (ceRNA) to sponge microRNA-142-3p (miR-142-3p) in modulating TWF1 expression in the gemcitabine resistance of pancreatic cancer. RESULTS: LncRNA SBF2-AS1 was highly expressed in pancreatic cancer tissues and cells. SBF2-AS1 was found to be associated with gemcitabine resistance in pancreatic cancer. Knock-down of SBF2-AS1 inhibited proliferation, epithelial-mesenchymal transition, while promoting apoptosis of gemcitabine resistant pancreatic cancer cells. SBF2-AS1 inhibited the expression of TWF1 by competitively binding with miR-142-3p in pancreatic cancer. CONCLUSION: Our study demonstrates that knock-down of SBF2-AS1 inhibits the expression of TWF1 by competitively binding with miR-142-3p to induce gemcitabine resistance in pancreatic cancer. METHODS: Expression of SBF2-AS1 was tested in pancreatic cancer tissues and cells. Construction of AsPC-1/GEM and PANC-1/GEM cells with low expression of SBF2-AS1 was performed to determine the biological behaviors of drug-resistant cells. AsPC-1 and PANC-1 cells expressing SBF2-AS1 and/or miR-142-3p were constructed and treated with different concentrations of gemcitabine to detect the sensitivity of the cells to gemcitabine. The binding relationship between SBF2-AS1 and miR-142-3p and between miR-142-3p and TWF1 were determined.

Effect of Celastrus orbiculatus in inhibiting Helicobacter pylori induced inflammatory response by regulating epithelial mesenchymal transition and targeting miR-21/PDCD4 signaling pathway in gastric epithelial cells.

BACKGROUND: The extract of Celastrus orbiculatus (COE) have been studied for anti-Helicobacter pylori (H. pylori) activity and anti-cancer effects in vitro and in vivo. However, the molecular mechanism by which COE inhibits H. pylori-induced inflammatory response has not been fully elucidated so far. METHODS: The effects of COE on viability, morphological changes, inflammatory cytokine secretion, protein and mRNA expression were analyzed by MTT assay, enzyme-linked immunosorbent assay (ELISA), immunofluorescence, western blot and real-time PCR (RT-PCR), respectively. The methylation level of programmed cell death 4 (PDCD4) promoter was investigated by methylation-specific PCR. (MSP) . RESULTS: COE effectively inhibited the H.pylori-induced inflammatory response by regulating epithelial-mesenchymal transition (EMT). The methylation level of PDCD4 promoter was suppressed by COE, which increased the expression ofPDCD4. Moreover, COE could inhibit microRNA-21 (miR-21) expression, as shown by an enhancement of its target gene PDCD4. Furthermore, both miR-21 over-expression and PDCD4 silencing attenuated the anti-inflammatory effect. of COE. CONCLUSIONS: COE inhibits H. pylori induced inflammatory response through regulating EMT, correlating with inhibition of miR-21/PDCD4 signal pathways in gastric epithelial cells.

Interfacial Effects on the Band Edges of Ta3N5 Photoanodes in an Aqueous Environment: A Theoretical View.

Ta3N5, as a fascinating photoanode for solar hydrogen production, is expected to split water without any bias, because its band edge potentials straddle H2O redox potentials. Unfortunately, Ta3N5 photoanodes can split water only when a bias of at least 0.6-0.9 V is applied. It means that they exhibit an onset potential as high as 0.6-0.9 VRHE (reversible hydrogen electrode). In this study, density functional theory calculations show that the band edge potentials of Ta3N5 have a shift of approximately -0.42 eV relative to vacuum level when exposed to water. The increased ratio of dissociated water at Ta3N5-water interface will further make the band edge potentials shift -0.85 eV relative to vacuum level, implying the anodic shifts of the onset potential for water oxidation. The findings may reveal the mystery of the unexpectedly high onset potential of Ta3N5, as high as 0.6-0.9 VRHE.

Brucine Suppresses Vasculogenic Mimicry in Human Triple-Negative Breast Cancer Cell Line MDA-MB-231.

Vasculogenic mimicry (VM) with the pattern of endothelial independent tubular structure formation lined by aggressive tumor cells mimics regular tumor blood vessels to ensure robust blood supply and correlates with the proliferation, invasion, metastasis, and poor prognosis of malignant tumors, which was demonstrated to be a major obstacle for resistance to antiangiogenesis therapy. Therefore, it is urgent to discover methods to abrogate the VM formation of tumors, which possesses important practical significance for improving tumor therapy. Brucine is a traditional medicinal herb extracted from seeds of Strychnos nux-vomica L. (Loganiaceae) exhibiting antitumor activity in a variety of cancer models. In the present study, the effect of brucine on vasculogenic mimicry and the related mechanism are to be investigated. We demonstrated that, in a triple-negative breast cancer cell line MDA-MB-231, brucine induced a dose-dependent inhibitory effect on cell proliferation along with apoptosis induction at higher concentrations. The further study showed that brucine inhibited cell migration and invasion with a dose-dependent manner. Our results for the first time indicated that brucine could disrupt F-actin cytoskeleton and microtubule structure, thereby impairing hallmarks of aggressive tumors, like migration, invasion, and holding a possibility of suppressing vasculogenic mimicry. Hence, the inhibitory effect of brucine on vasculogenic mimicry was further verified. The results illustrated that brucine significantly suppressed vasculogenic mimicry tube formation with a dose-dependent effect indicated by the change of the number of tubules, intersections, and mean length of tubules. The in-depth molecular mechanism of vasculogenic mimicry suppression induced by brucine was finally suggested. It was demonstrated that brucine inhibited vasculogenic mimicry which might be through the downregulation of erythropoietin-producing hepatocellular carcinoma-A2 and matrix metalloproteinase-2 and metalloproteinase-9.

miR-122 Targets X-Linked Inhibitor of Apoptosis Protein to Sensitize Oxaliplatin-Resistant Colorectal Cancer Cells to Oxaliplatin-Mediated Cytotoxicity.

BACKGROUND/AIMS: Although oxaliplatin is one of the most effective chemotherapeutic drugs used to treat colorectal cancer (CRC), long-term administration usually induces acquired drug resistance during the course of treatment. Thus, there is an urgent need to explore novel strategies to improve the efficiency of cancer therapy. The aim of this study was to explore the effect of microRNA-122 (miR-122) on reversing oxaliplatin resistance in CRC. METHODS: The expression of miR-122 in CRC cells was examined by quantitative reverse transcriptase real-time PCR. The cytotoxicity of oxaliplatin against CRC cells was evaluated by Cell Counting Kit-8 assays. Mitochondrial membrane potentials and cell apoptotic rates were measured by flow cytometry. Cellular protein expression and interactions were detected by western blot and co-immunoprecipitation. RESULTS: Established oxaliplatin-resistant SW480 and HT29 cells (SW480/OR and HT29/OR) expressed significantly higher levels of X-linked inhibitor of apoptosis protein (XIAP) and lower levels of miR-122 compared with normal SW480 and HT29 cells, respectively. Our results showed that the downregulation of miR-122 was responsible for the overexpression of XIAP in these oxaliplatin-resistant CRC cells. We then found that the recovery of miR-122 expression can sensitize SW480/OR and HT29/OR cells to oxaliplatin-mediated apoptosis through the inhibition of XIAP expression. CONCLUSION: Upregulation of XIAP in CRC cells is responsible for the acquired resistance to oxaliplatin. Furthermore, miR-122 reversed oxaliplatin resistance in CRC by targeting XIAP.

Effects of Celastrus orbiculatus on Epithelial Mesenchymal Transition in Gastric Mucosal Epithelial Cells by Inhibiting Lgr5 Expression from Rats with Gastric Precancerous Lesions.

The extract of Celastrus orbiculatus (COE) has been shown to possess anti-Helicobacter pylori (H. pylori) activity and anticancer effects in vitro and in vivo. However, the molecular mechanism by which COE on precancerous lesions of gastric cancer (PLGC) has not been fully elucidated so far. The purpose of this study is to evaluate the effect and mechanism of COE in the rat model of PLGC, after the rat model of PLGC was successfully constructed. The effects of COE in gastric mucosa of rats with PLGC were tested using routine pathology and a transmission electron microscope (TEM) analysis. The protein and mRNA expression levels of epithelial mesenchymal transition (EMT) markers (E-cadherin, N-cadherin and Vimentin) and leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) were detected adopting techniques of immunohistochemistry (IHC), real-time PCR (RT-PCR) and western blot assays. The body weight of PLGC rats was significantly higher in the COE group than that in the untreated group. The process of PLGC was significantly reversed after COE treatment, shown by observing the changes of histopathological morphology and ultrastructure. Gastric mucosal epithelial cells in COE high dose (COE-H) group showed significantly higher expression levels of E-cadherin, and lower expression levels of N-cadherin, Vimentin and Lgr5 than those of the untreated group. COE could suppress the spatial distribution of Lgr5[Formula: see text] cell changes in PLGC rats. These findings suggested that the therapeutic mechanisms of COE in treating PLGC might be related with its effects on reversing the EMT process and inhibiting Lgr5 expression.

Celastrus orbiculatus extract triggers apoptosis and autophagy via PI3K/Akt/mTOR inhibition in human colorectal cancer cells.

Celastrus orbiculatus is used as a folk medicine in China for the treatment of numerous diseases. The ethyl acetate extract of Celastrus orbiculatus (COE) also displays a wide range of anti-cancer activities in the laboratory. However, the effectiveness of COE-induced autophagy and its mechanism of action in colorectal cancer cells have not been investigated thus far. The present study analyzed the effect of COE on HT-29 cell viability, apoptosis and autophagy using MTT assay, flow cytometry, transmission electron microscopy and western blotting. Additionally, the autophagy inhibitor 3-methyladenine and the autophagy inducer rapamycin were used to further explore the effects of COE-induced autophagy in HT-29 cells. The present study also examined whether the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (p70S6K) signaling pathway was involved in the regulation of COE-induced autophagy. The results revealed that COE inhibited HT-29 cell proliferation and decreased cell survival in a time- and dose-dependent manner, and that COE possessed the ability to induce both apoptosis and autophagy in HT-29 cells. Furthermore, autophagy and apoptosis induced by COE synergized to inhibit colorectal cancer growth. In addition, COE treatment decreased the phosphorylation of Akt and its downstream effectors mTOR and p70S6K. Taken together, these results demonstrate that both autophagy and apoptosis were activated during COE treatment of HT-29 cells, and that COE-induced autophagy decreases the viability of HT-29 cells via a mechanism that may depend on the PI3K/Akt/mTOR/p70S6K signaling pathway. Furthermore, compounds that induce autophagy administered in combination with COE may be an attractive strategy for enhancing the anti-tumor potency of COE in colorectal cancer.

Chemotherapeutic Response and Prognosis among Lung Cancer Patients with and without Depression.

PURPOSE: The current study examined quality of life, progression of disease, and survival rate during chemotherapy in newly diagnosed non-small cell lung cancer (NSCLC) patients with depression (n=48) and without depression (n=78). Further, the study explored the hypothesis that the survival benefit resulted from the chemotherapy of docetaxel and cisplatin (the DC regimen). PATIENTS AND METHODS: In total, 126 patients with newly diagnosed NSCLC participated in a cross-sectional study of DC chemotherapy integrated with standard oncology care in depression and non-depression groups. The health-related quality of life (HR-QOL) was assessed using the quality of life questionnaire for Chinese cancer patients receiving chemobiotherapy (QLQ-CCC). Depression was self-rated using the Zung Self-Rating Depression Scale (Z-SDS). Both HR-QOL and Z-SDS were completed before the first and after the last cycle of chemotherapy. Association between depression and quality of life, treatment responses, adverse effects and survival rate was considered positive at the significance level of p<0.05. Pearson and Spearman correlation coefficient, t-test and other statistical analysis were performed using the SPSS software version 13.0 for Windows. RESULTS: In total, 126 lung cancer patients were evaluated, 38% had a diagnosis of depression. The presence of depression was associated with reduced quality of life, increased progression of disease, nausea and fatigue and reduced survival rate by nearly 90 days on follow-up. Therefore, depression significantly predicted worse survival (P=0.009).In addition, the chemotherapy DC regimen did not appear to improve the quality of life in depressed patients (SDS 94.96±18.14 before chemotherapy vs. SDS 100.04±16.61 after therapy, P=0.155). In a secondary analysis, there was a positive relationship between depression and nausea and fatigue but there was no significant difference in hematologic toxicities between the depression and non-depression groups. CONCLUSION: Depression was associated with worse survival in patients with newly diagnosed NSCLC. Also, the chemotherapy DC regimen did not improve quality of life in depressed patients and the data do not support the hypothesis that treatment responses of NSCLC patients with depression mediated the observed survival benefit from the DC regimen. There were more cases of progressed disease in the depressed group. Findings suggest that NSCLC patients with depression are at increased risk for decline in HR-QOL and survival rate during chemotherapy than patients without depression.

Antimetastatic effects of Celastrus orbiculatus on human gastric adenocarcinoma by inhibiting epithelial-mesenchymal transition and NF-κB/snail signaling pathway.

AIM OF THE STUDY: Celastrus orbiculatus has been used as a folk medicine in China for the treatment of many diseases. In the laboratory, the ethyl acetate extract of Celastrus orbiculatus (COE) displays a wide range of anticancer functions. However, the inhibition of the metastasis mechanism of COE in gastric cancer cells has not been investigated so far. The present study was undertaken to determine if the antimetastatic effects of COE were involved in inhibition of the epithelial-mesenchymal transition (EMT) of human gastric adenocarcinoma SGC-7901 cells. METHODS: The adhesion, invasion, and migration of SGC-7901 cells were determined by COE treatment in vitro, using Matrigel-coated plate, transwell membrane chamber, and wound healing models, respectively. In vivo, the growth-inhibiting and antimetastatic effects of COE on the nude mice model of gastric cancer were tested and the mechanisms were explored. The expression of EMT markers and nuclear factor κB (NF-κB)/Snail signaling pathway were evaluated by using western blotting and immunohistochemistry. RESULTS: Treatment with COE dose-dependently inhibited the proliferation, adhesion, invasion, and migration of SGC-7901 cells in vitro, which was realized by enhancing the expression of E-cadherin and reducing N-cadherin and vimentin expression. Moreover, COE suppressed the activation of NF-κB/Snail signaling pathway induced by tumor necrosis factor-α. In addition, COE effectively suppressed tumor growth and metastasis in the nude mice model due to reduced expression of N-cadherin, vimentin, NF-κB p65, and Snail and increased expression of E-cadherin in the tumor tissues. CONCLUSION: Our findings provided new evidence that COE is an effective inhibitor of metastatic potential of SGC-7901 cells through suppression of EMT and NF-κB/Snail signal pathway. Based on these findings, COE may be considered a novel anticancer agent for the treatment of metastasis in gastric cancer.

Research on the efficacy of Celastrus Orbiculatus in suppressing TGF-ß1-induced epithelial-mesenchymal transition by inhibiting HSP27 and TNF-α-induced NF-κ B/Snail signaling pathway in human gastric adenocarcinoma.

BACKGROUND: Celastrus orbiculatus has been used as a folk medicine in China for the treatment of many diseases. In the laboratory, the ethyl acetate extract of Celastrus orbiculatus (COE) displays a wide range of anticancer functions. However, the inhibition of the metastasis mechanism of COE in gastric cancer cells has not been investigated so far. METHODS: The present study was undertaken to determine if the anti-metastasis effect of COE was involved in inhibiting of epithelial-mesenchymal transition (EMT) of human gastric adenocarcinoma SGC-7901 cells. In vitro, a well-established experimental EMT model involving transforming growth factor ß1 (TGF-ß1) was applied. Viability, invasion and migration, protein and mRNA expression of tumor cells were analyzed by MTT assay, transwell assay, western blot and real-time PCR, respectively. The molecular targets of COE in SGC-7901 cells were investigated by two-dimensional gel electrophoresis (2-DE) and MALDI-TOF-TOF mass spectrometer. Overexpression of heat shock protein 27 (HSP27) was performed by transfected with the recombinant retroviral expression plasmid. In vivo, the anti-metastasis mechanisms of COE in the peritoneal gastric cancer xenograft model was explored and the effect was tested. RESULTS: The non-cytostatic concentrations of COE effectively inhibited TGF-ß1 induced EMT process in SGC-7901 cells, which is characterized by prevented morphological changes, increased E-cadherin expression and decreased Vimentin, N-cadherin expression. Moreover, COE inhibited invasion and migration induced by TGF-ß1. Using a comparative proteomics approach, four proteins were identified as differently expressed, with HSP27 protein being one of the most significantly down-regulated proteins induced by COE. Moreover, the activation of nuclear factor κB (NF-κB)/Snail signaling pathway induced by tumor necrosis factor-α (TNF-α) was also attenuated under the pretreatment of COE. Interestingly, overexpression of HSP27 significantly decreases the inhibitory effect of COE on EMT and the NF-κB/Snail pathway. Furthermore, COE significantly reduced the number of peritoneal metastatic nodules in the peritoneal gastric cancer xenograft model. CONCLUSIONS: Taken together, these results suggest that COE inhibits the EMT by suppressing the expression of HSP27, correlating with inhibition of NF-κB/Snail signal pathways in SGC-7901 cells. Based on these results, COE may be considered a novel anti-cancer agent for the treatment of metastasis in gastric cancer.