Moxibustion improves motor function by down-regulating SNX5 and inhibiting ferroptosis in neurons of corpus striatum in mice with Parkinson's disease. / 艾灸调控SNX5å¯¹å¸•é‡‘æ£®ç— æ¨¡åž‹å°é¼ ç¥žç»å ƒé“æ­»äº¡çš„å½±å“.

OBJECTIVES: To explore the effect of moxibustion on the expression of sorting nexin 5 (SNX5), glutathione peroxidase (GPX4) and ferritin heavy chain (FTH1) in the corpus striatum in mice with Parkinson's disease (PD), so as to explore its mechanisms underlying improvement of PD by ameliorating ferroptosis in the substantia nigra striatum. METHODS: C57BL/6J mice were randomly divided into normal, sham operation, model, and moxibustion groups, with 10 mice in each group. The PD model was established by unilateral injection of 6-hydroxydopamine (3.5 µL) into the right medial forebrain bundle (AP=-1.2 mm, ML=-1.3 mm, DV=-4.75 mm). The mice in the moxibustion group received moxibustion at "Baihui"(GV20) and "Sishencong"(EX-HN1) for 20 min each time, once a day, 6 times a week for 4 weeks. After the intervention, mice received apomorphine rotation behavior detection and pole climbing test. The expression of tyrosine hydroxylase (TH) in the substantia nigra was detected by immunofluorescence, the contents of Fe2+, malondialdehyde (MDA), the ratio of glutathione/oxidized glutathione (GSH/GSSG) in the corpus striatum were detected by using photocolorimetric method, and the expression levels of SNX5 (endocytosomal protein), GPX4 (one of the key targets for inhibiting ferroptosis) and FTH1 proteins and mRNAs in the corpus striatum were detected by Western blot and qPCR, respectively. RESULTS: Behavior tests showed that the pole climbing time and number of body rotation were significantly increased in the model group relevant to the sham operation group (P<0.01), and strikingly decreased in the moxibustion group relevant to the model group (P<0.01). The immunofluorescence intensity of TH in the substantia nigra, the ratio of GSH/GSSG, and the expression levels of GPX4 and FTH1 mRNAs and proteins in the corpus striatum were markedly decreased (P<0.01, P<0.05), while the contents of Fe2+ and MDA and the expression levels of SNX5 mRNA and protein in the corpus striatum significantly increased in the model group relevant to the sham operation group (P<0.01, P<0.05). Compared with the model group, the decreased immunofluorescence intensity of TH, GSH/GSSH, and the expression levels of GPX4 and FTH1 mRNAs and proteins, and the increased contents of Fe2+ and MDA and the expression levels of SNX5 mRNA and protein were reversed in the moxibustion group relevant to the model group (P<0.01, P<0.05). CONCLUSIONS: Moxibustion may improve motor dysfunction in PD mice, which may be related to its effects in down-regulating the expression of SNX5, promoting the synthesis of GSH, decreasing the contents of Fe2+ and MDA, up-regulating the ratio of GSH/GSSG and the expression of GPX4 and FTH1 mRNAs and proteins in the corpus striatum, and inhibiting the occurrence of ferroptosis.

Facile Synthesis of a SiOx-Graphite Composite toward Practically Accessible High-Energy-Density Lithium-Ion Battery Anodes.

SiOx-based material is a promising candidate for lithium-ion batteries (LIBs) owing to its high theoretical capacity. The inherent disadvantages of poor electronic conductivity and large volume variation can be solved by constructing the outermost carbon layer and reserving internal voids. However, the practical application of SiOx/C composites remains a great challenge due to the unsatisfactory energy density. Herein, we propose a facile synthetic approach for fabricating SNG/H-SiOx@C composites, which are constructed by amorphous carbon, hollow SiOx (H-SiOx), and spherical natural graphite (SNG). H-SiOx alleviates volume expansion, while amorphous carbon promotes Li+ migration and stable solid electrolyte interphase (SEI) formation. The as-prepared SNG/H-SiOx@C demonstrates a high reversible capacity (465 mAh g-1), excellent durability (93% capacity retention at 0.5C after 500 cycles), lower average delithiation potential than SNG (0.143 V after 500 cycles), and a 14% gravimetric energy density improvement at a loading level of 4.5 mg cm-2. Even at a compacted density of 1.5 g cm-3, the SNG/H-SiOx@C anode presents a modest volume deformation of 14.3% after 100 cycles at 0.1C.

Moxibustion treatment for Parkinson's disease: study protocol for a randomized controlled trial.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder and seriously affects quality of life globally. Moxibustion is widely used to treat neurodegenerative diseases in the clinic and has achieved a beneficial clinical effect. However, strict control and high-quality randomized controlled trials are still lacking. Therefore, this trial aims to evaluate the clinical efficacy and safety of moxibustion in patients with PD and preliminarily explore the underlying mechanism. METHODS: This is a randomized, single-blind and placebo-controlled trial design in which 70 eligible participants will be randomly divided into a moxibustion group and a sham moxibustion group. Baihui (DU20) and Sishenchong (EX-HN1) are selected for both groups. The treatment will be performed for 30 min per session, two sessions a week for 8 weeks. The mean change in MDS-UPDRS scores (including MDS-UPDRS II, III subscale scores and total scores) from baseline to the observation points will be the primary outcome. The secondary outcomes will include scores on the Parkinson's Disease Questionnaire-39 (PDQ-39), Fatigue Severity Scale (FSS), Parkinson Disease Sleep Scale (PDSS), Montreal Cognitive Assessment (MoCA), and Self-Rating Depression Scale (SDS) as well as the Wexner constipation score. All the above outcomes will be assessed at 4 and 8 weeks. Laboratory blood biochemical analysis and functional magnetic resonance imaging (fMRI) will be conducted at baseline and at the end of treatment to explore the potential mechanisms of moxibustion in regulating PD. DISCUSSION: In conclusion, the results of this trial will reveal whether moxibustion is effective for treating motor and nonmotor symptoms in PD. This trial will also preliminarily explore the underlying mechanism of the regulatory effect of moxibustion in PD, which will contribute to providing a theoretical basis for the treatment of PD. TRIAL REGISTRATION: ClinicalTrials.gov ChiCTR2000029745. Registered on 9 August 2021.

Dietary vitamin E intake and risk of Parkinson's disease: a cross-sectional study.

Objective: Current evidence on the association between dietary vitamin E intake and the risk of Parkinson's disease (PD) is limited. The aim of the study was to explore the association of dietary vitamin E intake with PD in the United States among adults over 40 years. Methods: We conducted a cross-sectional study with data collected from National Health and Nutrition Examination Survey (NHANES) from 2009 to 2018. A total of the sample of 13,340 participants were included. To identify the different characteristics of the participants, we utilized propensity score matching (PSM) to reduce the effects of selection bias and confounding variables. Weighted univariate and multivariable logistic regression were used to examine the association between dietary vitamin E intake and PD before and after matching. Then, restricted cubic spline (RCS) was used to visually describe the possible non-linear relationships. Finally, we employed the subgroup analysis to further investigate the relationship between dietary vitamin E intake and PD. Results: According to the weighted univariate and multivariable logistic regression analysis, vitamin E intake was inversely associated with the risk of PD before and after matching. The results of RCS analysis revealed no non-linear inverse relationship between vitamin E intake and PD before and after matching. The subgroup analysis showed that age may influence the negative association between vitamin E and PD (P < 0.05 for interaction). Conclusion: Among participants over 40 years of age, vitamin E intake was negatively associated with the risk of PD. Our data may support the supplementation of vitamin E to be used as an intervention strategy for the occurrence of PD.

Effect of acupuncture for non-motor symptoms in patients with Parkinson's disease: A systematic review and meta-analysis.

Background: Although non-motor symptoms of Parkinson's disease (PD) are serious, effective treatments are still lacking. Acupuncture may have clinical benefits for non-motor symptoms of PD patients, but high-quality evidence supporting this possibility is still limited. Hence, we conducted this meta-analysis to evaluate the effect of acupuncture treatment on non-motor symptoms in patients with PD. Methods: Randomized controlled trials (RCTs) of acupuncture treatment for PD were retrieved from the following electronic databases: Medline (OVID), Embase (OVID), Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese BioMedical Literature Database, Chonqing VIP (CQVIP), and Wangfang database. Studies evaluating non-motor symptoms of PD were retrieved. Methodological quality was assessed using the Cochrane Handbook for Systematic Reviews of Interventions. Results: A total of 27 RCTs were included, among which 8 outcomes related to non-motor symptoms were evaluated. The results showed that acupuncture combined with medication had benefits for PD-related insomnia relative to medication alone or sham acupuncture [standardized mean difference (SMD) = 0.517; 95% confidence interval (CI) = 0.242-0.793; p = 0.000], and acupuncture treatment had benefits at 8 weeks (SMD = 0.519; 95% CI = 0.181-0.857; p = 0.003). Regarding depression, acupuncture treatment was more effective (SMD = -0.353; 95% CI = -0.669 to -0.037; p = 0.029) within 2 months (SMD = -0.671; 95% CI = -1.332 to -0.011; p = 0.046). Regarding cognition, quality of life, and Unified Parkinson's Disease Rating Scale (UPDRS) I and II scores, acupuncture treatment was effective [SMD = 0.878, 95% CI = 0.046-1.711, p = 0.039; SMD = -0.690, 95% CI = -1.226 to -0.155, p = 0.011; weighted mean difference (WMD) = -1.536, 95% CI = -2.201 to -0.871, p = 0.000; WMD = -2.071, 95% CI = -3.792 to -0.351, p = 0.018; respectively]. A significant difference was not found in terms of PD-related constipation. Only one study evaluated PD-related fatigue. Conclusion: The results of the analysis suggested that acupuncture treatment could ameliorate the symptoms of depression, quality of life, cognition, total mentation, behavior and mood, and activities of daily living in PD patients. Nevertheless, more prospective, well-designed RCTs with larger sample sizes are required to confirm our findings.

Sorting Nexin 5 Plays an Important Role in Promoting Ferroptosis in Parkinson's Disease.

Parkinson's disease (PD) is a common neurodegenerative disease in the elderly, which is related to brain iron metabolism disorders. Ferroptosis is a newly discovered iron-dependent programmed cell death mode, which has been considered an essential mechanism of PD pathogenesis in recent years. However, its underlying mechanisms have not been fully understood. In the present study, the PD rat model and PD cell model were induced by 6-hydroyxdopamine (6-OHDA). The results showed that the expression of Sorting Nexin 5 (SNX5) and the level of ferroptosis will increase after treatment with 6-OHDA. Consistent with these results, ferroptosis inducer erastin synergistically reduced the expression of glutathione peroxidase 4 (GPX4) and increased the expression of SNX5 in the PD cell model, while ferroptosis inhibitor ferrostatin-1 (Fer-1) inhibited the decrease of GPX4 and the increase of SNX5 in the PD cell model. Knockdown of SNX5 in PC-12 cells could reduce intracellular lipid peroxidation and accumulation of Fe2+ and significantly inhibit the occurrence of ferroptosis. In conclusion, the present study suggested that SNX5 promotes ferroptosis in the PD model, thus providing new insights and potential for research on the pharmacological targets of PD.

Covalent organic framework-based porous materials for harmful gas purification.

Covalent organic frameworks (COFs) with 2D or 3D networks are a class of novel porous crystalline materials, and have attracted more and more attention in the field of gas purification owing to their attractive physicochemical properties, such as high surface area, adjustable functionality and structure, low density, and high stability. However, few systematic reviews about the application statuses of COFs in gas purification are available, especially about non-CO2 harmful gases. In this review, the recent progress of COFs about the capture, catalysis, and detection of common harmful gases (such as CO2, NOx, SO2, H2S, NH3 and volatile pollutants) were comprehensively discussed. The design strategies of COF functional materials from porosity adjustment to surface functionalization (including bottom-up approach, post-synthetic approach, and blending with other materials) for certain application were summarized in detail. Furthermore, the faced challenges and future research directions of COFs in the harmful gas treatment were clearly proposed to inspire the development of COFs.

Experimental Models of Cognitive Impairment for Use in Parkinson's Disease Research: The Distance Between Reality and Ideal.

Parkinson's disease (PD) is the second most common neurodegenerative disease. Cognitive impairment is one of the key non-motor symptoms of PD, affecting both mortality and quality of life. However, there are few experimental studies on the pathology and treatments of PD with mild cognitive impairment (PD-MCI) and PD dementia (PDD) due to the lack of representative models. To identify new strategies for developing representative models, we systematically summarized previous studies on PD-MCI and PDD and compared differences between existing models and diseases. Our initial search identified 5432 articles, of which 738 were duplicates. A total of 227 articles met our inclusion criteria and were included in the analysis. Models fell into three categories based on model design: neurotoxin-induced, transgenic, and combined. Although the neurotoxin-induced experimental model was the most common type that was used during every time period, transgenic and combined experimental models have gained significant recent attention. Unfortunately, there remains a big gap between ideal and actual experimental models. While each model has its own disadvantages, there have been tremendous advances in the development of PD models of cognitive impairment, and almost every model can verify a hypothesis about PD-MCI or PDD. Finally, our proposed strategies for developing novel models are as follows: a set of plans that integrate symptoms, biochemistry, neuroimaging, and other objective indicators to judge and identify that the novel model plays a key role in new strategies for developing representative models; novel models should simulate different clinical features of PD-MCI or PDD; inducible α-Syn overexpression and SH-SY5Y-A53T cellular models are good candidate models of PD-MCI or PDD.

Moxibustion Protects Dopaminergic Neurons in Parkinson's Disease through Antiferroptosis.

Ferroptosis is associated with neural degeneration of dopaminergic neurons in Parkinson's disease (PD). However, how to control the level of ferroptosis in PD remains unclear. Clinically, moxibustion has been used to treat PD and has an apparent therapeutic effect on improving the motor symptoms of PD. In the present study, the PD rat model was constructed by two-point stereotactic 6-hydroxydopamine injection. Then, moxibustion was used to treat the PD rats. The expression of glutathione peroxidase 4 (GPX4) and Ferritin Heavy Chain 1 (FTH1), the level of reactive oxygen species (ROS), and the morphology of mitochondrial were detected to evaluate the level of ferroptosis. The results showed that moxibustion treatment of Shi's moxa sticks could reduce the behavioral score, alleviate the level of ferroptosis, decrease mitochondrial damage, and improve dopaminergic neuron survival. In conclusion, the present study results indicated that Shi's moxa sticks could effectively suppress the level of ferroptosis, thereby improving the survival of dopaminergic neurons in the SNpc of PD rats, which may provide a promising complementary and alternative therapy for PD patients.

miR­335 promotes ferroptosis by targeting ferritin heavy chain 1 in in vivo and in vitro models of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease characterized by the selective loss of dopaminergic neurons in the substantia nigra (SN). In a previous study, the authors demonstrated that ferritin heavy chain 1 (FTH1) inhibited ferroptosis in a model of 6­hydroxydopamine (6­OHDA)­induced PD. However, whether and how microRNAs (miRNAs/miRs) modulate FTH1 in PD ferroptosis is not yet well understood. In the present study, in vivo and in vitro models of PD induced by 6­OHDA were established. The results in vivo and in vitro revealed that the levels of the ferroptosis marker protein, glutathione peroxidase 4 (GPX4), and the PD marker protein, tyrosine hydroxylase (TH), were decreased in the model group, associated with a decreased FTH1 expression and the upregulation of miR­335. In both the in vivo and in vitro models, miR­335 mimic led to a lower FTH1 expression, exacerbated ferroptosis and an enhanced PD pathology. The luciferase 3'­untranslated region reporter results identified FTH1 as the direct target of miR­335. The silencing of FTH1 in 6­OHDA­stimulated cells enhanced the effects of miR­335 on ferroptosis and promoted PD pathology. Mechanistically, miR­335 enhanced ferroptosis through the degradation of FTH1 to increase iron release, lipid peroxidation and reactive oxygen species (ROS) accumulation, and to decrease mitochondrial membrane potential (MMP). On the whole, the findings of the present study reveal that miR­335 promotes ferroptosis by targeting FTH1 in in vitro and in vivo models of PD, providing a potential therapeutic target for the treatment of PD.

Corrigendum: Experimental Models of Cognitive Impairment for Use in Parkinson's Disease Research: The Distance Between Reality and Ideal.

[This corrects the article DOI: 10.3389/fnagi.2021.745438.].

Reinforcing Behaviors of Sulfur-Containing Silane Coupling Agent in Natural Rubber-Based Magnetorheological Elastomers with Various Vulcanization Systems.

Magnetorheological elastomers (MRE) is known as an intelligent material constituted of a rubber matrix as well as soft magnetic particles. Silane coupling agents are used to raise the interplay between the inorganic particles and rubber matrix. Silane coupling agent, bis-[-3-(trimethylsilyl propyl)tetra sulfide] (Si69), was picked for comparison of its reinforcing efficiency in the MRE with various vulcanization systems: a conventional (CV), semi-efficient (semi-EV), and efficient (EV) vulcanization system. The outcome illustrated that not only was there improved Si69 surface hydrophobicity of the magnetic particles, but also enhanced Si69 in the interplay between the rubber matrix and magnetic particles. On one hand, the saturated induced magnetic modulus and zero magnetic field modulus of MRE was increased in the vulcanization system, and the loss factor was reduced after the magnetic particles were modified by Si69. On the other hand, the effect of Si69 on the MRE depended on the vulcanization system. The Si69 provided better enhancements in the EV system due to effects of the sulfur contribution of Si69.

FTH1 Inhibits Ferroptosis Through Ferritinophagy in the 6-OHDA Model of Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of dopaminergic neurons associated with dysregulation of iron homeostasis in the brain. Ferroptosis is an iron-dependent cell death process that serves as a significant regulatory mechanism in PD. However, its underlying mechanisms are not yet fully understood. By performing RNA sequencing analysis, we found that the main iron storage protein ferritin heavy chain 1 (FTH1) is differentially expressed in the rat 6-hydroyxdopamine (6-OHDA) model of PD compared with control rats. Our present work demonstrates that FTH1 is involved in iron accumulation and the ferroptosis pathway in this model. Knockdown of FTH1 in PC-12 cells significantly inhibited cell viability and caused mitochondrial dysfunction. Moreover, FTH1 was found to be involved in ferritinophagy, a selective form of autophagy involving the degradation of ferritin by ferroptosis. Overexpression of FTH1 in PC-12 cells impaired ferritinophagy and downregulated microtubule-associated protein light chain 3 and nuclear receptor coactivator 4 expression, ultimately suppressing cell death induced by ferroptosis. Consistent with these findings, the ferritinophagy inhibitors chloroquine and bafilomycin A1 inhibited ferritin degradation and ferroptosis in 6-OHDA-treated PC-12 cells. This entire process was mediated by the cyclic regulation of FTH1 and ferritinophagy. Taken together, these results suggest that FTH1 links ferritinophagy and ferroptosis in the 6-OHDA model of PD, and provide a new perspective and potential for a pharmacological target in this disease.

Therapeutic Efficiency of an External Chinese Herbal Formula of Mammary Precancerous Lesions by BATMAN-TCM Online Bioinformatics Analysis Tool and Experimental Validation.

Ruyan Neixiao Cream (RYNXC), a patented Chinese herbal formula, was reported to have the effect of treating mammary precancerous disease. In this study, we predicted the potential targets, pathways, and diseases of the ingredients contained in each herbal of RYNXC and constructed an ingredients-targets-diseases network. Then, we analyzed molecular mechanisms of this Chinese herbal formula by MCF-10AT cells and model rats of breast precancerous lesions. BATMAN-TCM prediction showed that ESR1, PGR, PTGS2, EGFR, and Src were mRNA targets of RYNXC. Our results suggested that RYNXC transdermal fluid downregulated ESR1, PGR, PTGS2, EGFR, and Src expression at gene and protein level in MCF-10AT cells. In the rat breast precancerous lesions model, high and low dose RYNXC could also significantly reduce genes and proteins expression of ESR1, PGR, PTGS2, EGFR, and Src. Taken together these data indicate that RYNXC targets multiple molecules responsible for breast precancerous lesion and is an effective Chinese herbal formula. So RYNXC may be a promising external drug for breast precancerous lesions.

Draft Genome of a Blister Beetle Mylabris aulica.

Mylabris aulica is a widely distributed blister beetle of the Meloidae family. It has the ability to synthesize a potent defensive secretion that includes cantharidin, a toxic compound used to treat many major illnesses. However, owing to the lack of genetic studies on cantharidin biosynthesis in M. aulica, the commercial use of this species is less extensive than that of other blister beetle species in China. This study reports a draft assembly and possible genes and pathways related to cantharidin biosynthesis for the M. aulica blister beetle using nanopore sequencing data. The draft genome assembly size was 288.5 Mb with a 467.8 Kb N50, and a repeat content of 50.62%. An integrated gene finding pipeline performed for assembly obtained 16,500 protein coding genes. Benchmarking universal single-copy orthologs assessment showed that this gene set included 94.4% complete Insecta universal single-copy orthologs. Over 99% of these genes were assigned functional annotations in the gene ontology, Kyoto Encyclopedia of Genes and Genomes, or Genbank non-redundant databases. Comparative genomic analysis showed that the completeness and continuity of our assembly was better than those of Hycleus cichorii and Hycleus phaleratus blister beetle genomes. The analysis of homologous orthologous genes and inference from evolutionary history imply that the Mylabris and Hycleus genera are genetically close, have a similar genetic background, and have differentiated within one million years. This M. aulica genome assembly provides a valuable resource for future blister beetle studies and will contribute to cantharidin biosynthesis.

Jianpi Bushen, a Traditional Chinese Medicine Therapy, Combined with Chemotherapy for Gastric Cancer Treatment: A Meta-Analysis of Randomized Controlled Trials.

Objective. To investigate the effects of Jianpi Bushen (JPBS), a traditional Chinese medicine that is used to invigorate the spleen and tonify the kidney, combined with chemotherapy for the treatment of gastric cancer. Methods. Literature retrieval was performed in PubMed, EMBASE, Cochrane Library, MEDLINE, CNKI, Wanfang Data Information Site, and VIP from inception to October 2017. Randomized controlled trials to evaluate the effects of JPBS combined with chemotherapy were identified. The primary reported outcomes were KPS (Karnofsky Performance Status), clinical curative efficiency, immune function, blood system, and nonhematologic system. Review Manager 5.3 (RevMan 5.3) was used for data analysis, and the quality of the studies was also appraised. Results. A total of 26 studies were included with 3098 individuals. The results of the meta-analysis indicated that treatment of gastric cancer with the combination of JPBS and chemotherapy resulted in better outcomes compared to chemotherapy alone. Conclusion. Evidence from the meta-analysis suggested that JPBS combined with chemotherapy has a positive effect on gastric cancer treatment. However, additional rigorously designed and large sample randomized controlled trials are required to confirm the efficacy and safety of this treatment.

Integrative analysis of lncRNAs and miRNAs with coding RNAs associated with ceRNA crosstalk network in triple negative breast cancer.

Triple negative breast cancer (TNBC) is a particular subtype of breast malignant tumor with poorer prognosis than other molecular subtypes. Currently, there is increasing focus on long non-coding RNAs (lncRNAs), which can act as competing endogenous RNAs (ceR-NAs) and suppress miRNA functions involved in post-transcriptional regulatory networks in the tumor. Therefore, to investigate specific mechanisms of TNBC carcinogenesis and improve treatment efficiency, we comprehensively integrated expression profiles, including data on mRNAs, lncRNAs and miRNAs obtained from 116 TNBC tissues and 11 normal tissues from The Cancer Genome Atlas. As a result, we selected the threshold with |log2FC|>2.0 and an adjusted p-value >0.05 to obtain the differentially expressed mRNAs, miRNAs and lncRNAs. Hereafter, weighted gene co-expression network analysis was performed to identify the expression characteristics of dysregulated genes. We obtained five co-expression modules and related clinical feature. By means of correlating gene modules with protein-protein interaction network analysis that had identified 22 hub mRNAs which could as hub target genes. Eleven key dysregulated differentially expressed micro RNAs (DEmiRNAs) were identified that were significantly associated with the 22 hub potential target genes. Moreover, we found that 14 key differentially expressed lncRNAs could interact with the key DEmiRNAs. Then, the ceRNA crosstalk network of TNBC was constructed by utilizing key lncRNAs, key miRNAs, and hub mRNAs in Cytoscape software. We analyzed and described the potential characteristics of biological function and pathological roles of the TNBC ceRNA co-regulatory network; also, the survival analysis was performed for each molecule. These findings revealed that ceRNA crosstalk network could play an important role in the development and progression for TNBC. In addition, we also identified that some molecules in the ceRNA network possess clinical correlation and prognosis.

Eugenol inhibits oxidative phosphorylation and fatty acid oxidation via downregulation of c-Myc/PGC-1ß/ERRα signaling pathway in MCF10A-ras cells.

Alteration in cellular energy metabolism plays a critical role in the development and progression of cancer. Targeting metabolic pathways for cancer treatment has been investigated as potential preventive or therapeutic methods. Eugenol (Eu), a major volatile constituent of clove essential oil mainly obtained from Syzygium, has been reported as a potential chemopreventive drug. However, the mechanism by which Eu regulates cellular energy metabolism is still not well defined. This study was designed to determine the effect of Eu on cellular energy metabolism during early cancer progression employing untransformed and H-ras oncogene transfected MCF10A human breast epithelial cells. Eu showed dose-dependent selective cytotoxicity toward MCF10A-ras cells but exhibited no apparent cytotoxicity in MCF10A cells. Treatment with Eu also significantly reduced intracellular ATP levels in MCF10A-ras cells but not in MCF10A cells. This effect was mediated mainly through inhibiting oxidative phosphorylation (OXPHOS) complexs and the expression of fatty acid oxidation (FAO) proteins including PPARα, MCAD and CPT1C by downregulating c-Myc/PGC-1ß/ERRα pathway and decreasing oxidative stress in MCF10A-ras cells. These results indicate a novel mechanism involving the regulation of cellular energy metabolism by which Eu may prevent breast cancer progression.

Expression of Beclin1 in the colonic mucosa tissues of patients with ulcerative colitis.

To investigate the expression of Beclin1 in the colonic mucosa tissue of patients with ulcerative colitis (UC), which acts as a regulator of autophagy and might play a part in the disease progression potentially. A total of 112 patients were selected from September 2013 to November 2014, and their colonic mucosal tissues were collected as the subject of study. Among them, 75 cases were diagnosed with ulcerative colitis (UC), 37 cases were diagnosed with irritable bowel syndrome (IRS) during the same time, which was set as the control group. The mucosal tissues were processed with ELISA and IHCA to measure the expression level of Beclin1, and correlation analysis was performed to demonstrate its role in the disease progression. The expression level pf Beclin1 was significantly higher in the UC patients compared with the control group (P<0.05). Meanwhile, it's positively correlated with the severity of disease, the endoscopic classification and the pathologic staging results, which has statistical significance (P<0.05). Beclin1 was expressed at a higher level in UC patients, and correlated with the severity of the disease, indicating the abnormal regulation of autophagy in the disease progression.

[Small intestine motility and gastrointestinal hormone levels in irritable bowel syndrome].

OBJECTIVE: To investigate the relationship between interdigestive migrating motor complex (MMC) and plasma gastrointestinal hormones in patients with diarrhea or constipation-predominant irritable bowel syndrome (IBS) to elucidate the pathophysiology of IBS. METHODS: A small intestine manometry was used to record the MMC cycles for at least 4-6 h in 19 IBS patients and 10 healthy volunteers. The plasma gastrointestinal hormone levels were examined according to altered MMC phases. RESULTS: Compared with the healthy controls, IBS-D patients exhibited shortened duration of the small intestinal MMC cycle, prolonged phase III duration with greater amplitude, as well as faster propagation velocity, whereas the contrary alterations were found in IBS-C patients. The peak plasma motilin level occurred in phase III of the MMC cycle. The plasma somatostatin level was higher in IBS groups than in the healthy controls, but comparable between the diarrhea and constipation groups. Plasma 5-hydroxytryptamine showed periodical fluctuations with the phases of MMC cycles, reaching the peak level in phase II. IBS-D patients had higher 5-hydroxytryptamine levels than IBS-C patients and the healthy controls. CONCLUSIONS: Plasma hormone levels are correlated with the MMC cycles, and the hormone level changes and small intestine motility disorder may play important roles in IBS pathophysiology.