Metabolomic and transcriptomic analysis of flavonoids biosynthesis mechanisms in mulberry fruit (Hongguo 2) under exogenous hormone treatments.

The mulberry fruit is prized for its superior nutrition value and abundant color due to its high flavone content. To enhance comprehension of flavone biogenesis induced by external hormones, we sprayed exogenous ethylene (ETH), indoleacetic acid (IAA) and spermine (SPM) on mulberry fruit (Hongguo 2) during its color-changed period. The levels of anthocyanin, titratable acid, soluble sugar and endogenous hormones were determined after hormone treatment, integrated transcriptome and metabolome analysis were performed for mechanism exploration. Our results indicated that exogenous ETH, SPM, and IAA play important roles in mulberry ripening, including acid reduction, sugar increase and flavonoid synthesis.

[Corrigendum] FKBP11 protects intestinal epithelial cells against inflammation­induced apoptosis via the JNK­caspase pathway in Crohn's disease.

Subsequently to the publication of the above article, the authors realized that Fig. 4 in their paper had been assembled containing two erroneously placed gel slices; essentially, the GAPDH bands featured in Fig. 4A had also been included in Fig. 5, and the data for the FKBP11 bands in Fig. 4A had also been included to show the GRP78 bands in Fig. 4. The authors were able to revisit their original data and to correct the data that had been featured incorrectly in Fig. 4. The corrected version of Fig. 4, now showing the true data for the GRP78 protein bands in Fig. 4C and the correct GAPDH protein bands for Fig. 4A, is shown on the next page. Note that these errors did not significantly affect the results or the conclusions reported in this paper. All the authors agree to the publication of this Corrigendum, and are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to correct this error. Moreover, the authors apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 18: 4428­4438, 2018; DOI: 10.3892/mmr.2018.9485].

Risk Factors and Location of Intracranial Aneurysm Rupture in a Consecutive Chinese Han Population.

OBJECTIVE: The aim of the present study was to retrospectively analyze and investigate the clinical data of 704 cases of ruptured intracranial aneurysms (RIAs) and unruptured intracranial aneurysms (UIAs). The risk factors predicting aneurysm rupture were explored from the perspective of the clinical characteristics of intracranial aneurysm (IA). METHODS: The clinical data of 704 patients with RIAs (494 patients) and UIAs (210 patients) admitted to the Department of Neurosurgery of Tianjin Medical University General Hospital and Tianjin Fifth Central Hospital between January 2016 and May 2022 were analyzed. A detailed analysis of sex, age, history, personal history, drug intake, and site of aneurysm occurrence was performed. Age was analyzed in segments and strata, and parameters with significant differences in the preliminary analysis results were analyzed by logistic regression to predict factors associated with the risk of aneurysm rupture. RESULTS: Among 494 patients with RIA (70.2%) and 210 patients with UIA (29.8%), the logistic regression showed that IA location appeared to be the most significant factor associated with RIA (OR, 95% CI: internal carotid artery (ICA), reference; anterior communicating artery,27.864,12.548-61.878; posterior communicating artery,12.408,6.658-23.124; anterior cerebral artery,5.804,2.333-14.440; middle cerebral artery,9.284,4.599-18.744; posterior circulation arteries, 4.224,2.011-8.871). Age was not a significant factor associated with RIA in the model and Hyperlipidemia (OR: 0.365; 95% CI: 0.171-0.779), Atherosclerosis (OR: 0.277; 95% CI: 0.172-0.446) and Multiple aneurysms (OR: 0.275; 95% CI: 0.177-0.425) patients were less likely to have RIA.IA location and age were the best predictors of RIA using the model. CONCLUSIONS: The present findings indicated that hyperlipidemia and atherosclerosis have a protective effect on aneurysm rupture, and different anatomical sites of IA may be risk factors for the occurrence of IA rupture. Among the anatomical sites of IA, the anterior communicating artery and posterior communicating artery have a higher fracture risk.

Characteristics of endoplasmic reticulum stress in colorectal cancer for predicting prognosis and developing treatment options.

BACKGROUND: An increasing body of evidence supports an essential role for endoplasmic reticulum stress (ERS) in colorectal cancer (CRC). In this study, we developed an ERS-related genes (ERSRGs) model to aid in the prognostic evaluation and treatment of CRC patients. METHODS: The training set and validation set data were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. ERSRGs were obtained from the GeneCards database. A prognostic risk scoring model was constructed using the least absolute shrinkage and selection operator (LASSO) along with univariate Cox regression analysis. To further predict the probability of survival for patients at 1, 2, and 3 years, a nomogram was devised. The advantages of the prognostic risk score model in screening patients' sensitive to chemotherapy and immunotherapy were analyzed by drug sensitivity analysis and immune correlation analysis. Finally, hub genes associated with poor prognosis in the risk model were screened by Protein-protein interaction (PPI) network and their expression was validated using clinical specimens. RESULTS: A risk model for overall survival (OS) was developed using 16 ERSRGs associated with prognosis. Through analyses, we demonstrated a high degree of reliability for the prognostic risk scoring model. The constructed nomograms performed well in predicting patient survival over 1, 3, and 5 years. The calibration curve and decision curve analysis (DCA) supported a high degree of accuracy for the model. Patients in the low-risk group had a lower IC50 for the common chemotherapy drug, 5-FU, and responded better to immunotherapy. hub poor prognostic genes were validated in CRC clinical specimens. CONCLUSION: We have identified and validated a new ERS prognostic marker that can accurately predict the survival status of CRC patients for clinicians and better provide personalized treatment plans.

Deep Learning Techniques in Intelligent Fault Diagnosis and Prognosis for Industrial Systems: A Review.

Fault diagnosis and prognosis (FDP) tries to recognize and locate the faults from the captured sensory data, and also predict their failures in advance, which can greatly help to take appropriate actions for maintenance and avoid serious consequences in industrial systems. In recent years, deep learning methods are being widely introduced into FDP due to the powerful feature representation ability, and its rapid development is bringing new opportunities to the promotion of FDP. In order to facilitate the related research, we give a summary of recent advances in deep learning techniques for industrial FDP in this paper. Related concepts and formulations of FDP are firstly given. Seven commonly used deep learning architectures, especially the emerging generative adversarial network, transformer, and graph neural network, are reviewed. Finally, we give insights into the challenges in current applications of deep learning-based methods from four different aspects of imbalanced data, compound fault types, multimodal data fusion, and edge device implementation, and provide possible solutions, respectively. This paper tries to give a comprehensive guideline for further research into the problem of intelligent industrial FDP for the community.

Hsa_circ_0000437 promotes pathogenesis of gastric cancer and lymph node metastasis.

Cellular communication between gastric cancer (GC) cells with different metastatic potentials and microenvironments and resultant cancer progression is not fully understood. Circular RNAs (circRNAs) and exosomal circRNAs are known to play extremely important regulatory roles in GC occurrence and progression. Here, we revealed significant differences in coronin-like actin-binding protein 1C (CORO1C) derived circRNA hsa_circ_0000437 between GC and para-cancer tissues. Hsa_circ_0000437 regulated GC cell proliferation, invasion, migration and apoptosis by targeting Ser/Arg-rich splicing factor 3 (SRSF3) and inhibiting programmed cell death 4 (PDCD4). The ectopic expression of hsa_circ_0000437 dramatically promoted tumor growth in nude mice in vivo. Furthermore, both gain-of-function and loss-of-function experiments demonstrated that hsa_circ_0000437 promoted human lymphatic endothelial cells (HLECs) invasion, migration, and tube formation in vitro and also promoted lymphangiogenesis and lymph node metastasis (LNM) in popliteal LNM model in vivo, when it was enriched in GC-secreted exosomes and transferred into HLECs. Mechanistically, exosomal hsa_circ_0000437 induced LNM via HSPA2-ERK signaling pathway independent of VEGF-C. Clinical data showed that exosomal hsa_circ_0000437 was enriched in the serum of GC patients, which was associated with LNM. In summary, these findings highlight the potential role of hsa_circ_0000437 as an outcome biomarker in GC patients with LNM, which may provide a novel target for GC therapy.

Dynamic Evolution of the Glymphatic System at the Early Stages of Subarachnoid Hemorrhage.

The early stages of subarachnoid hemorrhage (SAH) are extremely important for the progression and prognosis of this disease. The glymphatic system (GS) has positive implications for the nervous system due to its ability to clearance tau and amyloid-ß (Aß) protein. Previous studies have shown that GS dysfunction will appear after SAH. However, there is no systematic evaluation of the degree of damage and development process of GS function in the early stage after SAH. In this study, we evaluated the GS function and neurobehavioral in the sham, 6 h, 1, 3, and 7 days after SAH, respectively. Our results showed that the function of GS was severely attenuated in mice after SAH with a decreased polarity of Aquaporin-4 (AQP4), increased expression of AQP4, a linear correlation with the dystrophin-associated complex (DAC), the proliferation of reactive astrocytes, increased tau protein accumulation, and decreased neurological function. Collectively, these findings provide a comprehensive understanding of the functional changes of GS after SAH, provide references for subsequent scholars studying SAH, and suggest some potential mechanistic insight that affects AQP4 polarity and GS function.

Anti-Inflammatory Activity of Mulberry Leaf Flavonoids In Vitro and In Vivo.

Mulberry (Morus alba L.) is a flowering tree traditionally used in Chinese herbal medicine. Mulberry leaf flavonoids (MLFs) have been reported to exert important anti-inflammatory and antioxidant properties. The purpose of this study was to select the MLF with the best anti-inflammatory and antioxidative activities from MLFs eluted by different ethanol concentrations (30%, 50%, and 75%) and explore its pharmacological properties. Three types of MLFs inhibited the production of nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and inflammatory cytokines in lipopolysaccharide (LPS)-induced RAW 264.7 cells. All MLFs boosted the antioxidative capacity by decreasing the reactive oxygen species (ROS) production and the scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals and improving the metal ion chelating activity and reducing power. The results revealed that the MLFs eluted by 30% ethanol exhibited the best anti-inflammatory and antioxidative activities. A nontargeted metabolomic analysis was used to analyze 24 types of differential flavonoids between the MLFs. Quercetin, kaempferol, and their derivatives in 30%MLF were more abundant than the other two MLFs. Furthermore, we evaluated the pharmacological activities of 30%MLF in dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) mice. The 30%MLF could alleviate the clinical symptoms, reduce the secretion of inflammatory cytokines, and inhibit the activation of the inflammatory pathway in DSS-induced colitis mice. This study will provide valuable information for the development of MLFs eluted by 30% ethanol as a functional food.

MiR-205-5p Functions as a Tumor Suppressor in Gastric Cancer Cells through Downregulating FAM84B.

MicroRNAs (miRNAs) participate in the formation of multiple diseases, including gastric cancer (GC), through modulating specific targets. Here, we explored the functions and regulatory mechanisms of miR-205-5p in GC. MiR-205-5p levels were detected in GC cells through qRT-PCR. Besides, the role of miR-205-5p in cell proliferation, cell apoptosis, cell cycle, cell invasion, and metastasis was assessed through CCK-8 assay, colony formation, flow cytometry, scratch assay, transwell, and western blot. Moreover, the Starbase website was used to predict the target gene of miR-205-5p, further verified by a dual-luciferase reporter assay. Furthermore, the functional effects of the family with sequence similarity 84 member B (FAM84B) on GC mediated by miR-205-5p upregulation were further investigated. MiR-205-5p expression was decreased in GC cells. Upregulation of miR-205-5p inhibited cell proliferation and metastasis and induced apoptosis and cycle arrest of GC cells. Moreover, FAM84B was predicted and confirmed as a target of miR-205-5p and negatively related to miR-205-5p. Mechanically, FAM84B overexpression partially rescued the functional effects of miR-205-5p upregulation on GC cell progression. This study suggests the potential of miR-205-5p/FAM84B as novel targets for the treatment of GC.

Optimized Ensiling Conditions and Microbial Community in Mulberry Leaves Silage With Inoculants.

Mulberry leaves (ML) are a promising alternative fodder source due to their high protein content and the abundance of active components. A test of three inoculants in various combinations revealed that high-quality ML silage was produced at an inoculum ratio of 1:1:0 (50% Saccharomyces cerevisiae, 50% Lactobacillus plantarum, and 0% Bacillus subtilis). Using dry matter (DM) loss, pH, ammonia-N and amino acid contents, total antioxidant activity, and total flavonoids content to evaluate silage quality, this inoculant mixture was shown to produce high-quality silage within a range of inoculum size (5-15%), moisture contents (50-67%), ensiling temperatures (27-30°C), and ensiling duration (14-30 days). A third trial comparing silages produced after 30 days at 28°C and 50% moisture content revealed that silage E, prepared using an L. plantarum inoculant alone, displayed the lowest DM loss and pH, and low bacterial diversity, and it was dominated by Lactobacillus (88.6%), with low abundance of Enterobacter (6.17%). In contrast, silage B5, prepared with equal ratios of L. plantarum and S. cerevisiae, was dominated by Enterococcus (67.16%) and Lactobacillus (26.94%), with less marked yeast persistence, and reducing the DM content from 50 to 40% altered these relative abundances to 5.47 and 60.61, respectively. Control silages produced without an inoculant had the highest pH and ammonia-N content (indicative of poor quality), had the lowest antioxidant activity, had higher bacterial diversity, and were dominated by Carnobacterium (74.28%) and Enterococcus (17.3%). In summary, ensiling of ML conditions with proper inoculants yielded high-quality silage with a favorable microbial community composition.

Transcriptomics and metabolomics analysis reveal the anti-oxidation and immune boosting effects of mulberry leaves in growing mutton sheep.

Introduction: Currently, the anti-oxidation of active ingredients in mulberry leaves (MLs) and their forage utilization is receiving increasing attention. Here, we propose that MLs supplementation improves oxidative resistance and immunity. Methods: We conducted a trial including three groups of growing mutton sheep, each receiving fermented mulberry leaves (FMLs) feeding, dried mulberry leaves (DMLs) feeding or normal control feeding without MLs. Results: Transcriptomic and metabolomic analyses revealed that promoting anti-oxidation and enhancing disease resistance of MLs is attributed to improved tryptophan metabolic pathways and reduced peroxidation of polyunsaturated fatty acids (PUFAs). Furthermore, immunity was markedly increased after FMLs treatment by regulating glycolysis and mannose-6-phosphate pathways. Additionally, there was better average daily gain in the MLs treatment groups. Conclusion: These findings provide new insights for understanding the beneficial effects of MLs in animal husbandry and provide a theoretical support for extensive application of MLs in improving nutrition and health care values.

Nimodipine Attenuates Early Brain Injury by Protecting the Glymphatic System After Subarachnoid Hemorrhage in Mice.

The glymphatic system (GS) plays an important role in subarachnoid hemorrhage (SAH). Nimodipine treatment provides SAH patients with short-term neurological benefits. However, no trials have been conducted to quantify the relationship between nimodipine and GS. We hypothesized that nimodipine could attenuate early brain injury (EBI) after SAH by affecting the function of the GS. In this study, we assessed the effects of nimodipine, a dihydropyridine calcium channel antagonist, on mice 3 days after SAH. The functions of GS were assessed by immunofluorescence and western blot. The effects of nimodipine were assessed behaviorally. Concurrently, correlation analysis was performed for the functions of GS, immunofluorescence and behavioral function. Our results indicated that nimodipine improved GS function and attenuated neurological deficits and brain edema in mice with SAH. Activation of the cAMP/PKA pathway was involved in this process. GS function was closely associated with perivascular AQP4 polarization, cortical GFAP/AQP4 expression, brain edema and neurobehavioral function. In conclusion, this study shows for the first time that nimodipine plays a neuroprotective role in the period of EBI after SAH in mice through the GS.

Aberrant expression of PI3K/AKT signaling is involved in apoptosis resistance of hepatocellular carcinoma.

Phosphatidylinositol 3-kinase (PI3K)/AKT signaling is a crucial pathway for cell survival and proliferation, which are regulated by several growth factors and activated receptors. Upregulated PI3K/AKT signaling molecules were reported in several cancers and they are associated with altered cellular functions, leading to oncogenesis. Here, we have examined the implications of elevated PI3K/AKT expression in the apoptosis resistance of human hepatocellular carcinoma (HCC) Huh7 cells. We showed that PI3K/AKT signaling is significantly upregulated in Huh7 cells by quantitative polymerase chain reaction and protein expression analysis. Also, perversely upregulated PI3K/AKT signaling Huh7 cells are highly resistant to treatment with chemotherapy drugs (docetaxel and sorafenib) and acquired apoptosis resistance through downregulation of tumor suppressor protein PTEN (phosphatase and tensin homolog deleted on chromosome ten). Hence, we have investigated the effect of PTEN overexpression on apoptosis induction in Huh7 cells. We showed that PTEN overexpressed Huh7 cells became more sensitive toward the aforesaid drugs and induced apoptotic cell death due to intracellular reactive oxygen species (ROS) generation. Concurrently, the overexpression of PTEN leads to the activation of mitochondria facilitated intrinsic apoptosis, evidenced by upregulated cytochrome C, caspase 3, and caspase 9. Collectively, our data suggest that the aberrant expression of PI3K/AKT signaling contributes to apoptosis resistance in HCC.

Comparative Proteomic Analysis of Tolerant and Sensitive Varieties Reveals That Phenylpropanoid Biosynthesis Contributes to Salt Tolerance in Mulberry.

Mulberry, an important woody tree, has strong tolerance to environmental stresses, including salinity, drought, and heavy metal stress. However, the current research on mulberry resistance focuses mainly on the selection of resistant resources and the determination of physiological indicators. In order to clarify the molecular mechanism of salt tolerance in mulberry, the physiological changes and proteomic profiles were comprehensively analyzed in salt-tolerant (Jisang3) and salt-sensitive (Guisangyou12) mulberry varieties. After salt treatment, the malondialdehyde (MDA) content and proline content were significantly increased compared to control, and the MDA and proline content in G12 was significantly lower than in Jisang3 under salt stress. The calcium content was significantly reduced in the salt-sensitive mulberry varieties Guisangyou12 (G12), while sodium content was significantly increased in both mulberry varieties. Although the Jisang3 is salt-tolerant, salt stress caused more reductions of photosynthetic rate in Jisang3 than Guisangyou12. Using tandem mass tags (TMT)-based proteomics, the changes of mulberry proteome levels were analyzed in salt-tolerant and salt-sensitive mulberry varieties under salt stress. Combined with GO and KEGG databases, the differentially expressed proteins were significantly enriched in the GO terms of amino acid transport and metabolism and posttranslational modification, protein turnover up-classified in Guisangyou12 while down-classified in Jisang3. Through the comparison of proteomic level, we identified the phenylpropanoid biosynthesis may play an important role in salt tolerance of mulberry. We clarified the molecular mechanism of mulberry salt tolerance, which is of great significance for the selection of excellent candidate genes for saline-alkali soil management and mulberry stress resistance genetic engineering.

Assessment of CD27 expression on T-cells as a diagnostic and therapeutic tool for patients with smear-negative pulmonary tuberculosis.

BACKGROUND: There is a global focus on illness diagnosis in smear-negative and latent tuberculosis infectious populations (SN-TB and LTBI). CD27 has been suggested to play a direct role in active TB. Little is known about smear-negative individuals. Here, we tried to investigate whether it has a role in smear-negative populations. The expression of CD27 and MTB-specific CD27 in CD4+ T cells ("CD27-CD4+" and "CD27-IFN-γ+CD4+") was evaluated in MTB-unexposed controls (HC), TB contacts (TB-C) and SN-TB individuals by flow cytometry. The sensitivity, specificity and AUC (area under curve) of "CD27-IFN-γ+CD4+" cells to distinguish SN-TBs from HCs and TB-Cs were determined by receiver operating characteristic (ROC) curve analysis. The clinical index was selected from the clinical laboratory and evaluated for correlation with "CD27-IFN-γ+CD4+" cells by Spearman statistical analysis. RESULTS: We observed that the percentages of "CD27-IFN-γ+CD4+" cells were significantly increased in the SN-TB group compared with the HC and TB-C groups (AUC was 0.88, sensitivity was 82.14%, specificity was 80.00%, and P < 0.0001). The percentage of "CD27-IFN-γ+CD4+" cells was negatively correlated with WBC (white blood cell count) (r = - 0.3019, P = 0.0182) and positively correlated with IgE (immunoglobulin E) (r = 0.2805, P = 0.0362). Furthermore, "CD27-IFN-γ+CD4+" cells were significantly decreased, especially in the > 50 years group, after clinical treatment. CONCLUSION: The present results demonstrated that the percentage of "CD27-IFN-γ+CD4+" cells might be a conceivable molecular indicator in the diagnosis of SN-TB and was influenced by its outcome of therapy.

Association of CDKN2A/CDKN2B Gene Polymorphisms with Increased Susceptibility to Intracranial Aneurysm in a Chinese Han Population.

OBJECTIVE: Several studies have reported that single-nucleotide polymorphisms (SNPs) of the CDKN2A/CDKN2B gene on chromosome 9p21.3 are associated with increased risk of intracranial aneurysm (IA). However, the association between IAs and SNPs of CDKN2A/CDKN2B in Chinese Han people is yet to be evaluated. This study examined the association of the SNPs rs10811661 and rs4977574 with IA in the Chinese Han population. METHODS: A total of 595 IA patients and 600 sex- and age-matched controls were enrolled in the study. Peripheral blood was collected and stored at -80°C until use. CDKN2A/CDKN2B was identified using polymerase chain reaction-ligase detection reaction. SNP genotyping was performed for rs10811661 and rs4977574 using a MassArray system. Associations between these two SNPs and IAs was tested with χ2 or Fisher's exact tests and multivariate logistic regression. RESULTS: rs10811661 and rs4977574 were significantly associated with IA. The frequency of rs10811661-T in IA was higher than in controls (OR 1.26, 95% CI 1.07-1.49; P<0.01). There was no significant difference in frequency of haplotype between control subjects and IA patients. CONCLUSION: rs10811661 and rs4977574 on 9p21.3 were strongly associated with genetic susceptibility to IA in the Chinese Han population, which emphasizes a need for further investigation.

Prognostic Value of the Pretreatment Systemic Immune-Inflammation Index in Patients with Colorectal Cancer.

BACKGROUND: Multiple studies have reported the significance of the systemic immune-inflammation index (SII) in the prognosis of colorectal cancer (CRC), but no consensus has yet been reached. The purpose of this study was to systematically assess the prognostic value of SII in patients with CRC. MATERIALS AND METHODS: We performed a systematic literature search in PubMed, Embase, and the Cochrane Library for eligible studies. The correlation between pretreatment SII and overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) in CRC patients was evaluated by combining the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Twelve studies involving 3919 patients were included. Comprehensive analysis results showed that high SII indicated poor OS in CRC patients (HR = 1.777, 95% CI: 1.328-2.376). Compared with patients with low SII values, patients with high SII had lower PFS (HR = 1.658, 95% CI: 1.189-2.311). Subgroup analysis further verified the above results. CONCLUSIONS: SII may be a noninvasive and powerful tool for predicting survival outcomes in CRC patients. However, more well-designed studies are needed to validate our findings.

Prognostic and clinicopathological significance of pretreatment mean platelet volume in cancer: a meta-analysis.

OBJECTIVE: Our study aimed to evaluate the prognostic and clinicopathological significance of pretreatment mean platelet volume (MPV) on cancer by using meta-analysis of published studies. DESIGN: Meta-analysis. DATA SOURCES: Relevant studies available before 22 December 2019 were identified by searching MEDLINE, EMBASE. ELIGIBILITY CRITERIA: All published studies that assessed the prognostic and clinicopathological significance of pretreatment MPV on cancer were included. DATA EXTRACTION AND SYNTHESIS: Studies were identified and extracted by two reviewers independently. The HR/OR and its 95% CIs of survival outcomes and clinicopathological parameters were calculated. RESULTS: A total of 38 eligible studies (41 subsets) with 9894 patients with cancer were included in the final meta-analysis. MPV level was not significantly associated with both overall survival (HR 0.98, 95% CI 0.84 to 1.14) and disease-free survival (HR 1.22, 95% CI 0.86 to 1.73) of patients with cancer. Neither advanced nor mixed-stage tumour patients showed significant association between MPV and overall survival (HR 1.36, 95% CI 0.96 to 1.94, HR 0.90, 95% CI 0.74 to 1.09). However, high MPV had the strongest relationship with poor overall survival (HR 2.01; 95% CI 1.08 to 3.41) in gastric cancer, followed by pancreatic cancer (HR 1.54; 95% CI 1.31 to 1.82). Whereas in the subgroup using receiver operating characteristic curve method to define cut-off values, low MPV was significantly related to poor overall survival (HR 0.78, 95% CI 0.64 to 0.95). In addition, MPV had no significant association with age (OR 0.96, 95% CI 0.90 to 1.02), sex (OR 1.04, 95% CI 1.00 to 1.09), depth of cancer invasion (OR 0.90, 95% CI 0.77 to 1.04) and tumour stage (OR 0.91, 95% CI 0.78 to 1.07). CONCLUSIONS: Pretreatment MPV level is of no clearly prognostic significance in cancers and no significant association with clinicopathological parameters of patients with cancers.

Methyl-indole inhibits pancreatic cancer cell viability by down-regulating ZFX expression.

This study explored the effect of methyl-indole on pancreatic cancer cell viability and investigated the mechanism involved. The viability of pancreatic cells showed a significant suppression on treatment with methyl-indole in dose-based manner. Treatment with 5 µM methyl-indole suppressed Capan-1 cell viability to 23%. The viability of Aspc-1 cells was reduced to 20% and those of MIApaCa-2 cells to 18% by 5 µM methyl-indole. The apoptotic proportion of Capan-1 cells was 67%, while as those of Aspc-1 and MIApaCa-2 cells increased to 72 and 77%, respectively, on treatment with 5 µM methyl-indole. The level of P13K, p-Tyr, p-Crkl and p-Akt was inhibited in the cells by methyl-indole. Moreover, methyl-indole also suppressed zinc-finger protein, X-linked mRNA and protein expression in tested cells. In summary, methyl-indole exhibits anti-proliferative effect on pancreatic cancer cells and induces apoptosis. It targeted ZFX expression and down-regulated P13K/AKT pathway in pancreatic cancer cells. Therefore, methyl-indole acts as therapeutic agent for pancreatic cancer and may be studied further.

Hydroxypyridinone-Coumarin Inhibits the Proliferation of MHCC97 and HepG2 Human Hepatocellular Carcinoma Cells and Down-Regulates the Phosphoinositide-3 Kinase Pathway.

BACKGROUND Worldwide, hepatocellular carcinoma (HCC) is one of the most commonly diagnosed malignant diseases and is the third leading cause of cancer-related death. This study aimed to investigate the effect of hydroxypyridinone-coumarin (HPC) on MHCC97 and HepG2 human HCC cells and the mechanisms involved. MATERIAL AND METHODS MHCC97 and HepG2 human HCC cells were cultured in vitro. An MTT cytotoxicity assay was used to assess cell viability and proliferation, with and without treatment with HPC. Cell autophagosomes were labeled with GFP-LC3 using confocal fluorescence microscopy. Western blot was used to measure protein expression. RESULTS HPC significantly reduced the cell proliferation rate in a concentration-dependent manner, with 2 µM of HPC resulting in a reduced proliferation rate of MHCC97 cells (by 36%) and HepG2 cells (by 29%) (P<0.02). HPC significantly reduced autophagy in MHCC97 and HepG2 cells. Western blot showed that treatment with HPC significant upregulated Atg5, beclin-1, LC3-phosphatidylethanolamine conjugate (LC3-II), and Atg-3, reduced p62 and Akt protein expression, and induced phosphorylation of ERK1/2. GFP-LC3B labeling in MHCC97 and HepG2 cells was increased following HPC treatment. CONCLUSIONS HPC induced autophagy and inhibited the proliferation of MHCC97 and HepG2 HCC cells in vitro and involved activation of ERK1/2 and down-regulation of the Akt pathway.