Search

Background: Green tea, mulberry leaf and corn silk are traditional herbs used in the prevention and treatment of diabetes in China for a long time, but their synergistic hypoglycemic effects and mechanisms remain unclear. Methods: The effective components of green tea, mulberry leaf and corn silk were extracted and enriched. Mixture design of experiments was used to study the influences of different combinations on the cell viability and glucose uptake level of L6 myoblasts, so as to determine the optimal synergistic hypoglycemic combination. The possible hypoglycemic mechanism of the optimal synergistic combination was explored by cytotoxicity assay, glucose uptake assay, and western blot. Results: Three polyphenol enrichment fractions of the herbs, 30% ethanol elution fraction of green tea (GT), 50% ethanol elution fraction of mulberry leaf (ML) and 60% ethanol elution fraction of corn silk (CS) were obtained. The antioxidant activities of GT-30%, ML-50% and CS-60% were superior to those of crude extracts, and showed strong potential in a-amylase and a-glucosidase inhibition activities. The optimal synergistic combination of crude extracts G7 (crude extract of green tea:crude extract of mulberry leaf:crude extract of corn silk = 1:5:3), polyphenol enrichment fractions R3 (GT-30%:ML-50%:CS-60% = 1:7:1) and monomers X2 (epigallocatechin gallate:morusin:formononetin = 3:1:2) were selected, respectively. G7, R3, and X2 showed promoting effects on the cell viability and glucose uptake of L6 myoblasts within the detected concentration range. In addition, G7, R3, and X2 could increase the expression levels of p-PI3K/PI3K and p-Akt/Akt in L6 myoblasts, and promote the translocation of Glut4, but G7 and R3 showed more significant effects. Conclusion: The synergistic hypoglycemic effects of green tea, mulberry leaf and corn silk had the characteristics of multiple-components and multiple-targets with p-PI3K/PI3K, p-Akt/Akt and the translocation of Glut4 signal pathways involved. The three traditional herbs might have the potential to be combined used for the prevention and treatment of diabetes based on the synergistic hypoglycemic effects. [ABSTRACT FROM AUTHOR]

Introduction: Microorganisms play a critical role in soil biogeochemical cycles, but it is still debated whether they influence soil biogeochemical processes through community composition and diversity or not. This study aims to investigate variation in bacterial community structure across different soils and its correlation to soil multifunctionality. Soil samples were collected from five typical farmland zones along distinct climatic gradients in China. Methods: The high-throughput sequencing (Illumina MiSeq) of 16S rRNA genes was employed to analyze bacterial community composition in each soil sample. Multivariate analysis was used to determine the difference in soil properties, microbial community and functioning, and their interactions. Results: Cluster and discrimination analysis indicated that bacterial community composition was similar in five tested soil samples, but bacterial richness combined with soil enzyme activities and potential nitrification rate (PNR) contributed most to the differentiations of soil samples. Mantel test analysis revealed that bacterial community composition and richness were more significantly shaped by soil nutrient conditions and edaphic variables than bacterial diversity. As for soil multifunctionality, soil microbial community level physiological profiles were little affected by abiotic and biotic factors, while soil enzymes and PNR were also significantly related to bacterial community composition and richness, in addition to soil N and P availability. Conclusion: Cumulatively, soil enzymes’ activities and PNR were greatly dependent on bacterial community composition and richness not diversity, which in turn were greatly modified by soil N and P availability. Therefore, in the future it should be considered for the role of fertilization in the modification of bacterial community and the consequent control of nutrient cycling in soil. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) is one of the diseases with high fatality rate. Berberine (BBR) is a monomer compound with various biological functions. And some studies have confirmed that BBR plays an important role in alleviating cardiomyocyte injury after MI. However, the specific mechanism is unclear. In this study, we induced a model of MI by ligation of the left anterior descending coronary artery and we surprisingly found that BBR significantly improved ventricular remodeling, with a minor inflammatory and oxidative stress injury, and stronger angiogenesis. Moreover, BBR inhibited the secretion of Wnt5a/β-catenin pathway in macrophages after MI, thus promoting the differentiation of macrophages into M2 type. In summary, BBR effectively improved cardiac function of mice after MI, and the potential protective mechanism was associated with the regulation of inflammatory responses and the inhibition of macrophage Wnt5a/β-catenin pathway in the infarcted heart tissues. Importantly, these findings supported BBR as an effective cardioprotective drug after MI. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is a neurodegenerative disorder caused by a mutation in the huntingtin (HTT) gene that results in the production of neurotoxic mutant HTT (mHTT) protein. Suppressing HTT production with antisense oligonucleotides (ASOs) is a promising treatment strategy for HD; however, the difficulty of delivering ASOs to deep brain structures is a major barrier for its clinical application. The glymphatic system of astrocytes involving aquaporin 4 (AQP-4) controls the entry of macromolecules from the cerebrospinal fluid into the brain. Mesenchymal stem cells (MSCs) target astrocytes to inhibit neuroinflammation. Here we examined the glymphatic distribution of ASO in the brain and the therapeutic potential of combining intravenously injection of mesenchymal stem cells (IV-MSC) and ASOs for the treatment of HD. Our results show that Cy3-labeled ASOs entered the brain parenchyma via the perivascular space following cisternal injection, but the brain distribution was significantly lower in AQP-4-/- as compared with wild-type mice. Downregulation of the AQP-4 M23 isoform was accompanied by decreased brain levels of ASOs in BACHD mice as well as an increase in astrogliosis and phosphorylation of nuclear factor κB (NF-κB) p65. IV-MSC treatment restored AQP-4 M23 expression, attenuated astrogliosis, and decreased NF-κB p65 phosphorylation; it also increased the brain distribution of ASOs and enhanced the suppression of mHTT in BACHD mice. These results suggest that modulating glymphatic activity using IV-MSC is a novel strategy for improving the potency of ASO in the treatment of HD. [ABSTRACT FROM AUTHOR]

Bone cancer pain is common in patients with advanced cancers as tumors metastasize to bone. Pathogenesis of bone cancer pain is complex and poorly understood which leads to inefficiency of clinical treatment. During pathological pain status, astrocytes are activated and release various inflammatory cytokines, which result in the development of peripheral and central sensitization. As energy factory, mitochondria undergo frequent fusion and fission and play essential role for astrocyte function. 2-bromopalmitate (2-BP) is an inhibitor of protein palmitoylation, and its function on bone cancer pain was unclear. In this article, we aimed to investigate the potential curative effects and mechanisms of 2-BP on bone cancer pain. Bone cancer pain rat model was established through intratibial inoculation of rat mammary gland carcinoma cells (MRMT-1) into the left tibia of Sprague-Dawley female rats. As a result, bone cancer pain rats exhibited bone destruction and sensitive nociceptive behavior. And increased leukocyte infiltration, activation of astrocytes, and imbalance of mitochondrial fission and fusion dynamics were observed in spinal cord of bone cancer pain rats. Intrathecal 2-BP administration significantly attenuated pain behavior of bone cancer pain rats. Meanwhile, 2-BP administration reduced spinal inflammation, reversed spinal mitochondrial fission and fusion dynamic imbalance, and further inhibited spinal mitochondrial apoptosis in bone cancer pain rats. In C6 cell level, 2-BP treatment decreased dynamin-related protein 1 expression and increased optic atrophy 1 expression in a dose-dependent manner and inhibited carbonyl cyanide 3-chlorophenylhydrazone (CCCP)-induced mitochondrial membrane potential change. These data illustrated that 2-BP attenuated bone cancer pain by reversing mitochondrial fusion and fission dynamic imbalance in spinal astrocytes. [ABSTRACT FROM AUTHOR]

The level of cerebellar activity in stroke patients has been shown to correlate with the extent of functional recovery. We reasoned that the cerebellum may be an important player in post-stroke rehabilitation. Because the neurons in the deep cerebellar nuclei (DCN) represent virtually all of the output from the cerebellum, in this study, using environmental enrichment (EE) to promote rehabilitation, we investigated the influence of the optogenetic neuronal modulation of DCN on EE-induced rehabilitation. We found that neuronal inhibition of the DCN almost completely blocked motor recovery in EE treated mice, but the stroke mice with neuronal activation of the DCN achieved a similar recovery level as those in the EE treated group. No difference was observed in anxiety-like behavior. Moreover, Htr2a in the DCN, the gene encoding 5-HT2A receptor, was shown to be a hub gene in the protein-protein interaction network identified using RNA-seq. This indicated that 5-HT2A receptor-mediated signaling may be responsible for DCN-dependent functional improvement in EE. We further verified this using the 5-HT2A receptor antagonist, MDL100907, to inhibit the function of 5-HT2A receptor in the DCN. This treatment resulted in impaired recovery in EE treated mice, who performed at a level as poor as the stroke-only group. Thus, this work contributes to an understanding of the importance of the DCN activation in EE-induced post-stroke rehabilitation. Attempts to clarify the mechanism of 5-HT2A receptor-mediated signaling in the DCN may also lead to the creation of a pharmacological mimetic of the benefits of EE-induced rehabilitation. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown that acupuncture is beneficial for the alleviation of chemotherapy-induced nausea and vomiting. However, there is a lack of clinical evidence concerning the effects of acupoint-matching on chemotherapy-induced nausea and vomiting.Methods/design: This is a parallel randomized controlled trial to evaluate the occurrence of nausea and vomiting after chemotherapy (the incidence of nausea and vomiting, frequency, VAS score, RINVR rating) as the main outcome for cancer. Quality of life, anxiety and depression scores are the secondary outcomes. Quality of life, anxiety and depression scores are the secondary phase. Use of remedy drugs, routine blood examination, and blood biochemical tests are the safety evaluation. We also compare the different effects of ST36 (single acupoint), CV12 (single acupoint), and ST36-CV12 matching groups.Discussion: The results of this trial are expected to explore the effects of matching different acupoints and to offer biologic plausibility for the use of acupuncture in the treatment of chemotherapy-induced nausea and vomiting (CINV).Trial Registration: This trial is registered with clinicaltrials.gov NCT02195921 , The date of registration was 17 July 2014. [ABSTRACT FROM AUTHOR]

The NF-κB signaling pathway plays a pivotal role in regulating the immune response and inflammation. However, it has been shown that NF-κB also has a major role in oncogenesis. Therefore, NF-κB inhibitors have been considered as potential drugs against cancer. Herein, we searched for NF-κB inhibitors from natural sources and identified mollugin from the roots of Rubia cordifolia L. as an inhibitor of NF-κB activation. We found that mollugin significantly inhibited the expression of an NF-κB reporter gene induced by tumor necrosis factor (TNF)-α in a dose-dependent manner. Moreover, mollugin inhibited TNF-α-induced phosphorylation and nuclear translocation of p65, phosphorylation and degradation of inhibitor of κB (IκBα), and IκB kinase (IKK) phosphorylation. Furthermore, we discovered that pretreatment of cells with mollugin prevented the TNF-α-induced expression of NF-κB target genes, such as genes related to proliferation (COX-2, Cyclin D1 and c-Myc), anti-apoptosis (Bcl-2, cIAP-1 and survivin), invasion (MMP-9 and ICAM-1), and angiogenesis (VEGF). We also demonstrated that mollugin potentiated TNF-α-induced apoptosis and inhibited proliferation of HeLa cells. We further demonstrated in vivo that mollugin suppressed the growth of tumor xenografts derived from HeLa cells. Taken together, mollugin may be a valuable candidate for cancer treatment by targeting NF-κB. [ABSTRACT FROM AUTHOR]

Background: The role of cancer cell FOXP3 in tumorigenesis is conflicting. We aimed to study FOXP3 expression and regulation, function and clinical implication in human non-small cell lung cancer (NSCLC). Methods: One hundred and six patients with histologically-confirmed NSCLC who underwent surgery were recruited for the study. Tumor samples and NSCLC cell lines were used to examine FOXP3 and its related molecules. Various cell functions related to tumorigenesis were performed. In vivo mouse tumor xenograft was used to confirm the in vitro results. Results: NSCLC patients with the high level of FOXP3 had a significant decrease in overall survival and recurrencefree survival. FOXP3 overexpression significantly induced cell proliferation, migration, and invasion, whereas its inhibition impaired its oncogenic function. In vivo studies confirmed that FOXP3 promoted tumor growth and metastasis. The ectopic expression of FOXP3 induced epithelial–mesenchymal transition (EMT) with downregulation of E-cadherin and upregulation of N-cadherin, vimentin, snail, slug, and MMP9. The oncogenic effects by FOXP3 could be attributed to FOX3-mediated activation of Wnt/β-catenin signaling, as FOXP3 increased luciferase activity of Topflash reporter and upregulated Wnt signaling target genes including c-Myc and Cyclin D1 in NSCLC cells. Coimmunoprecipitation results further indicated that FOXP3 could physically interacted with β-catenin and TCF4 to enhance the functions of β-catenin and TCF4, inducing transcription of Wnt target genes to promote cell proliferation, invasion and EMT induction. Conclusions: FOXP3 can act as a co-activator to facilitate the Wnt-b-catenin signaling pathway, inducing EMT and tumor growth and metastasis in NSCLC. [ABSTRACT FROM AUTHOR]

Background: Many patients experience nausea and vomiting during chemotherapy treatment. Evidence demonstrates that electroacupuncture is beneficial for controlling chemotherapy-induced nausea and vomiting (CINV). However, the acupoint or matching acupoint with the best efficacy for controlling CINV still remains unidentified. Methods/Design: This study consists of a randomized controlled trial (RCT) with four parallel arms: a control group and three electroacupuncture groups (one with Neiguan (PC6), one with Zhongwan (CV12), and one with both PC6 and CV12). The control group received standard antiemetic only, while the other three groups received electroacupuncture stimulation with different acupoints besides the standard antiemetic. The intervention is done once daily from the first day (day 1) to the fourth day (day 4) during chemotherapy treatment. The primary outcome measures include frequency of nausea, vomiting and retching. The secondary outcome measures are the grade of constipation and diarrhea, electrogastrogram, assessment of quality of life, assessment of anxiety and depression, and other adverse effects during the chemotherapy. Assessments are scheduled from one day pre-chemotherapy (day 0) to the fifth day of chemotherapy (day 5). Follow-ups are done from day 6 to day 21. Discussion: The aim of this study is to evaluate the efficacy and safety of electro-acupuncture with different acupoints in the management of CINV. Trial registration: The register number of randomized controlled trial is NCT02195908. The date of registration was 21 July 2014. [ABSTRACT FROM AUTHOR]

Background: Many patients experience nausea and vomiting during chemotherapy treatment. Evidence demonstrates that electroacupuncture is beneficial for controlling chemotherapy-induced nausea and vomiting (CINV). However, the acupoint or matching acupoint with the best efficacy for controlling CINV still remains unidentified. Methods/Design: This study consists of a randomized controlled trial (RCT) with four parallel arms: a control group and three electroacupuncture groups (one with Neiguan (PC6), one with Zhongwan (CV12), and one with both PC6 and CV12). The control group received standard antiemetic only, while the other three groups received electroacupuncture stimulation with different acupoints besides the standard antiemetic. The intervention is done once daily from the first day (day 1) to the fourth day (day 4) during chemotherapy treatment. The primary outcome measures include frequency of nausea, vomiting and retching. The secondary outcome measures are the grade of constipation and diarrhea, electrogastrogram, assessment of quality of life, assessment of anxiety and depression, and other adverse effects during the chemotherapy. Assessments are scheduled from one day pre-chemotherapy (day 0) to the fifth day of chemotherapy (day 5). Follow-ups are done from day 6 to day 21. Discussion: The aim of this study is to evaluate the efficacy and safety of electro-acupuncture with different acupoints in the management of CINV. [ABSTRACT FROM AUTHOR]

The mechanism responsible for the apoptotic effect induced by ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F) is not fully understood and its in vivo effect has not been tested. In this study, the effect and mechanism of 5F was investigated in cigarette smoking carcinogen 4-methylnitrosamino-1-3-pyridyl-butanone (NNK)-induced mouse lung tumor model and in cultured lung cancer cells NCI-H23 and CRL-2066. 5F were given to mice after they were treated with NNK for 18 weeks. The effect of 5F on the lung tumor formation was examined, and its side effect was monitored. Cell proliferation and apoptosis were determined through expression of PCNA, Bcl-2, Bax, and TUNEL assay in in vivo animal model. 5F significantly inhibited the NNK-induced lung tumors by inducing apoptosis and suppressing cell proliferation in vivo with minimal side effects. Cell culture experiments showed that 5F translocated Bax into the mitochondria, downregulated Bcl-2, activated caspase-9 and caspase-3, released cytochrome c into the cytosol, and translocated AIF from the mitochondria to the nucleus, which leading to G2-M cell cycle arrest and cell apoptosis. 5F also activated ERK1/2 and the inhibition of ERK1/2 suppressed 5F-mediated changes in apoptotic molecules. In addition to ERK1/2, 5F activated Akt. The inhibition of Akt further facilitated the apoptosis induced, suggesting that Akt activation was anti-apoptotic rather than pro-apoptotic. Collectively, 5F is effective against lung cancer in vivo with minimal side effects. It induces apoptosis in lung cancer through the mitochondrial-mediated pathway, in which the activation of ERK is critical. [ABSTRACT FROM AUTHOR]

Background 15-S-Hydroxyeicosatetraenoic acid (15(S)- HETE) and 13-S hydroxyoctadecadienoic acid (13S)- HODE), both of which are metabolites of 15 lipoxygenases (15-LOXs), are endogenous ligands for peroxisome proliferator-activated receptor gamma (PPARγ). The activation of PPARγ inhibits cell growth and induces apoptosis in some cancers. The role of 15(S)-HETE) and 13(S)-HODE in the development of lung cancer is not clear. Methods 15-LOXs, 15(S)-HETE and 13(S) HODE were monitored during the development of mouse lung tumours induced by the tobacco smoke carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and the levels of these markers were determined in 54 human non-small cell lung cancers. Results 15-LOXs, 15(S)-HETE and 13(S)-HODE levels were significantly reduced in human lung cancer tissue compared with non-tumour lung tissue (p¼0.011 and p¼0.022, respectively). In mouse experiments, 15(S)- HETE and 13(S)-HODE started to reduce at 26 and 30 weeks, respectively, after NNK treatment. The time frame of 15(S)-HETE reduction was in line with the decrease in 1 /15-LOX mRNA and protein. A significant difference in the number of tumours in NNK-treated mice and controls was not observed until week 34 (p<0.05) and week 38 (p<0.01). The reduction in 12/15-LOX and 15(S)-HETE therefore predated the appearance of lung tumour. Furthermore, PPARγ activity was decreased in NNK-treated mouse lungs compared with the control, and the decreased PPARγ activity occurred at the same time points as the reduction in 12/15-LOX and 15(S)-HETE. Conclusion These findings indicate that the reduction in 15-LOX, 15(S)-HETE and 13(S)-HODE results in the decreased PPARγ activity seen in lung tumours and contributes to the development of lung tumours induced by tobacco smoking. [ABSTRACT FROM AUTHOR]

Presents a study on the ability of hepatocyte growth factor (HGF) to reduce advancing lung fibrosis in mice which has a potential role for MMP-dependent myofibroblast apoptosis. Outcome of chronic respiratory failures and is histologically characterized by hyperplasia of interstitial myofibroblasts to deposit extracellular matrix; Method used to determine potential target cells of HGF in fibrotic murine lungs; Reason for examining the effects of HGF on myofibroblast survival, focusing on fibronectin and MMP-2/-9.