Showing papers by "Liaoning University of Traditional Chinese Medicine published in 2018"
TL;DR: The proposed 3D-LOC could provide a convenient and robust solution for the long-term safe perfusion culture of hepatic spheroids and be beneficial for a variety of potential applications including development of bio-artificial livers, disease modeling, and drug toxicity screening.
Abstract: Spheroid-based three-dimensional (3D) liver culture models, offering a desirable biomimetic microenvironment, are useful for recapitulating liver functions in vitro. However, a user-friendly, robust and specially optimized method has not been well developed for a convenient, highly efficient, and safe in situ perfusion culture of spheroid-based 3D liver models. Here, we have developed a biomimetic and reversibly assembled liver-on-a-chip (3D-LOC) platform and presented a proof of concept for long-term perfusion culture of 3D human HepG2/C3A spheroids for building a 3D liver spheroid model. On the basis of a fast and reversible seal of concave microwell-based PDMS–membrane–PDMS sandwich multilayer chips, it enables a high-throughput and parallel perfusion culture of 1080 cell spheroids in a high mass transfer and low fluid shear stress biomimetic microenvironment as well as allowing the convenient collection and analysis of the cell spheroids. In terms of reducing spheroid loss and maintaining cell morphology and viability in long-term perfusion culture, the cell spheroids in the 3D-LOC were more safe and efficient. Notably, the polarisation, liver-specific functions, and metabolic activity of the cell spheroids in 3D-LOC were also remarkably improved and exhibited better long-term maintenance over conventional perfusion methods. Additionally, a robust micromilling method that incorporates secondary PDMS coating techniques (SPCs) for fabricating V-shaped concave microwells was also developed. The V-shaped concave microwell arrays exhibited a higher distribution density and aperture ratio, making it easy to form large-scale and uniform-sized cell spheroids with minimum cell loss. In summary, the proposed 3D-LOC could provide a convenient and robust solution for the long-term safe perfusion culture of hepatic spheroids and be beneficial for a variety of potential applications including development of bio-artificial livers, disease modeling, and drug toxicity screening.
113 citations
TL;DR: It is suggested that BRB anthocyanins could modulate the composition of gut commensal microbiota, and changes in inflammation and the methylation status of the SFRP2 gene may play a central role in the chemoprevention of CRC.
Abstract: Freeze-dried black raspberry (BRB) powder is considered as a potential cancer chemopreventive agent. In this study, we fed azoxymethane (AOM)/dextran sodium sulfate (DSS)-treated C57BL/6J mice with a diet containing BRB anthocyanins for 12 weeks, and this led to a reduction in colon carcinogenesis. These animals had consistently lower tumor multiplicity compared with AOM/DSS-treated mice not receiving BRB anthocyanins. In AOM/DSS-treated mice, the number of pathogenic bacteria, including Desulfovibrio sp. and Enterococcus spp., was increased significantly, whereas probiotics such as Eubacterium rectale, Faecalibacterium prausnitzii and Lactobacillus were dramatically decreased, but BRB anthocyanins supplement could reverse this imbalance in gut microbiota. BRB anthocyanins also caused the demethylation of the SFRP2 gene promoter, resulting in increased expression of SFRP2, both at the mRNA and protein levels. Furthermore, the expression levels of DNMT31 and DNMT3B, as well as of p-STAT3 were downregulated by BRB anthocyanins in these animals. Taken together, these results suggested that BRB anthocyanins could modulate the composition of gut commensal microbiota, and changes in inflammation and the methylation status of the SFRP2 gene may play a central role in the chemoprevention of CRC.
110 citations
TL;DR: The potential anti-cancer effects of Andro are demonstrated, indicating that Andro could inhibit COX-2 expression through attenuating p300 HAT activity and suppress angiogenesis via VEGF pathway, and thereby could be developed as an antitumor agent for the treatment of breast cancer.
Abstract: Andrographolide (Andro), a diterpenoid lactone, has been used for treatment of various cancers with less adverse effects. However, the underlying mechanisms regarding its anti-tumor mechanism still remain unclear. Cell viability and proliferation were measured by CCK8 and CFSE dilution assay. The localization of p50/p65 or cytochrome c was determined using confocal immunofluorescence. Streptavidin-agarose pulldown or ChIP assays were used to detect the binding of multiple transactivators to COX-2 promoter. The promoter activity was examined by a dual-Luciferase reporter assay. The functions of Andro on COX-2-mediated angiogenesis were also investigated using human HUVEC cells through tube formation and spheroids sprouting assay. The in vivo anti-tumor efficacy of Andro was analyzed in xenografts nude mice. The results indicated that Andro could significantly inhibit the proliferation of human breast cancers, and suppress COX-2 expression at both protein and mRNA levels. Furthermore, Andro could dose-dependently inhibit COX-2-mediated angiogenesis in human endothelial cells. We have also found that Andro significantly promoted the activation of cytochrome c and activated caspase-dependent apoptotic signaling pathway. Our further explorations demonstrated that Andro inhibited the binding of the transactivators CREB2, C-Fos and NF-κB and blocked the recruitment of coactivator p300 to COX-2 promoter. Moreover, Andro could effectively inhibit the activity of p300 histone acetyltransferase (HAT), thereby attenuating the p300-mediated acetylation of NF-κB. Besides, Andro could also dramatically inhibit the migration, invasion and tubulogenesis of HUVECs in vitro. In addition, Andro also exhibited effective anti-tumor efficacy as well as angiogenesis inhibition in vivo. In current study, we explore the potential effects of Andro in suppressing breast cancer growth and tumor angiogenesis, as well as the precise mechanisms. This work demonstrated the potential anti-cancer effects of Andro, indicating that Andro could inhibit COX-2 expression through attenuating p300 HAT activity and suppress angiogenesis via VEGF pathway, and thereby could be developed as an antitumor agent for the treatment of breast cancer.
86 citations
TL;DR: XIST exerted regulatory function in resistance of DOX possibly through miR-124/SGK1 axis, shedding new light on developing promising therapeutic strategy to overcome chemoresistance in CRC patients.
Abstract: Background/aims Doxorubicin (DOX) is a widely used chemotherapeutic agent for colorectal cancer (CRC). However, the acquirement of DOX resistance limits its clinical application for cancer therapy. Mounting evidence has suggested that aberrantly expressed lncRNAs contribute to drug resistance of various tumors. Our study aimed to explore the role and molecular mechanisms of lncRNA X-inactive specific transcript (XIST) in chemoresistance of CRC to DOX. Methods The expressions of XIST, miR-124, serum and glucocorticoid-inducible kinase 1 (SGK1) mRNA in DOX-resistant CRC tissues and cells were detected by qRT-PCR or western blot analysis. DOX sensitivity was assessed by detecting IC50 value of DOX, the protein levels of P-glycoprotein (P-gp) and glutathione S-transferase-π (GST-π) and apoptosis. The interactions between XIST, miR-124 and SGK1 were confirmed by luciferase reporter assay, qRT-PCR and western blot. Xenograft tumor assay was used to verify the role of XIST in DOX resistance in CRC in vivo. Results XIST expression was upregulated and miR-124 expression was downregulated in DOX-resistant CRC tissues and cells. Knockdown of XIST inhibited DOX resistance of CRC cells, as evidenced by the reduced IC50 value of DOX, decreased P-gp and GST-π levels and enhanced apoptosis in XIST-silenced DOX-resistant CRC cells. Additionally, XIST positively regulated SGK1 expression by interacting with miR-124 in DOX-resistant CRC cells. miR-124 suppression strikingly reversed XIST-knockdown-mediated repression on DOX resistance in DOX-resistant CRC cells. Moreover, SGK1-depletion-elicited decrease of DOX resistance was greatly restored by XIST overexpression or miR-124 inhibition in DOX-resistant CRC cells. Furthermore, XIST knockdown enhanced the anti-tumor effect of DOX in CRC in vivo. Conclusion XIST exerted regulatory function in resistance of DOX possibly through miR-124/SGK1 axis, shedding new light on developing promising therapeutic strategy to overcome chemoresistance in CRC patients.
73 citations
TL;DR: Limited evidence suggested a potential survival benefit of transjugular intrahepatic portosystemic shunt in patients with hepatorenal syndrome but with a high incidence of hepatic encephalopathy.
60 citations
TL;DR: It is demonstrated that chrysophanol effectively suppresses breast cancer cell proliferation and facilitates chemosentivity through modulation of the NF-κB signaling pathway.
Abstract: Chrysophanol is an anthraquinone compound, which exhibits anticancer effects on certain types of cancer cells. However, the effects of chrysophanol on human breast cancer remain to be elucidated. The aim of the present study was to clarify the role of chrysophanol on breast cancer cell lines MCF‑7 and MDA‑MB‑231, and to identify the signal transduction pathways regulated by chrysophanol. MTT assay and flow cytometric analysis demonstrated that chrysophanol inhibited cell proliferation, and cell cycle progression in a dose‑dependent manner. The expression of cell cycle‑associated cyclin D1 and cyclin E were downregulated while p27 expression was upregulated following chrysophanol treatment at the mRNA, and protein levels. The Annexin V/propidium iodide staining assay results revealed that apoptosis levels increased following chrysophanol treatment. Chrysophanol upregulated caspase 3 and poly (ADP‑ribose) polymerase cleavage in both cell lines. Furthermore, chrysophanol enhanced the effect of paclitaxel on breast cancer cell apoptosis. In addition, chrysophanol downregulated apoptosis regulator Bcl‑2 protein, and transcription factor p65 and IκB phosphorylation. Inhbition of nuclear factor (NF)‑κB by ammonium pyrrolidine dithiocarbamate diminished the effect of chrysophanol on apoptosis and associated proteins. In conclusion, the results of the current study demonstrated that chrysophanol effectively suppresses breast cancer cell proliferation and facilitates chemosentivity through modulation of the NF-κB signaling pathway.
58 citations
TL;DR: Enteral nutrition within 48 hours after admission is efficient and safe for the patients with SAP or pSAP.
49 citations
22 Aug 2018
TL;DR: BANCR knockdown suppressed CRC progression and strengthened chemosensitization of CRC cells to ADR possibly by regulating miR-203/CSE1L axis, indicating that BANCR might be a promising target for CRC treatment.
Abstract: Colorectal cancer (CRC) is the third most common malignancy in the United States. Chemotherapeutic resistance is a massive obstacle for cancer treatment. The roles and molecular basis of long non-coding RNA BRAF-activated noncoding RNA (BANCR) in CRC progression and adriamycin (ADR) resistance have not been extensively identified. In this study, we found that BANCR and CSE1L expressions were upregulated in CRC tumor tissues. Meanwhile, CSE1L expression was correlated with depth of CRC. BANCR silencing suppressed cell proliferation and invasion capacity, increased apoptotic rate and potentiated cell sensitivity to ADR. CSE1L downregulation triggered a reduction of cell proliferation and invasion ability, and an increase of apoptosis rate and cell sensitivity to ADR. CSE1L overexpression attenuated si-BANCR-mediated anti-proliferation, anti-invasion and pro-apoptosis effects in CRC cells. BANCR acted as a molecular sponge of miR-203 to sequester miR-203 away from CSE1L in CRC cells, resulting in the upregulation of CSE1L expression. CSE1L knockdown inhibited expressions of DNA-repair-related proteins (53BP1 and FEN1) in HCT116 cells. BANCR knockdown also inhibited tumor growth and enhanced ADR sensitivity in CRC mice model. In conclusion, BANCR knockdown suppressed CRC progression and strengthened chemosensitization of CRC cells to ADR possibly by regulating miR-203/CSE1L axis, indicating that BANCR might be a promising target for CRC treatment.
47 citations
TL;DR: It is suggested that BCPR increases the survival of OHCAs, and it also help O HCAs whose initial rhythm is shockable, which is to say BCPR is also helpful when emergency department response time is short.
Abstract: For many years, bystander cardiopulmonary resuscitation (BCPR) has been considered as a favorable factor to improve survival of out-of-hospital cardiac arrests (OHCAs). To examine the effect of BCPR on the survival of OHCAs and whether BCPR might also improve survival when the initial rhythm of OHCAs is limited, we performed a meta-analysis on published observational studies. We did a systematic review to identify all studies published up to March, 2018, in any language, that reported the relation between BCPR and the survival of OHCAs. Using standard forms, two authors independently identified studies for inclusion and extracted information. The outcome was survival. Meta-regression was done to ascertain weighted factors for the outcomes. Data were extracted from 19 studies involving 232,703 patients. Firstly, pooled odds ratio (OR) from 16 cohort studies showed that BCPR was associated with improved chance of survival of OHCAs compared with NO-BCPR (OR 1.95, 95% confidence interval [CI]: 1.66–2.30). Secondly, from 8 cohort studies of OHCAs whose initial rhythm is limited, the pooled OR was 2.10 (95% CI, 1.68–2.63) of 6 articles for shockable rhythm and 1.07 (95% CI, 0.37–3.13) of 2 articles for non-shockable rhythm. Meta-regression showed a relation between the survival of OHCAs and BCPR was influenced by area (p < 0.05). Based on currently available evidence, the findings of this meta-analysis suggest that BCPR increases the survival of OHCAs, and it also help OHCAs whose initial rhythm is shockable. That is to say BCPR is also helpful when emergency department response time is short. Therefore global priority should be given to increasing the incidence of BCPR by evidence-based best practice.
46 citations
TL;DR: Loganin could attenuate inflammatory response induced by Aβ in BV‐2 microglia cells, partially through deactivating the TLR4/TRAF6/NF‐κB axis, and the anti‐inflammatory effects of loganin were attenuated whenTLR4 signaling pathway was re‐activated by LPS.
46 citations
TL;DR: The OCT-modified daunorubicin plus dihydroartemisinin liposomes could prevent breast cancer invasion, hence providing a possible strategy for treatment of metastatic breast cancer.
Abstract: Tumor invasion is considered a major promoter in the initiation of tumor metastasis, which is supposed to cause most cancer-related deaths. In the present study, octreotide (OCT)-modified daunorubicin plus dihydroartemisinin liposomes were developed and characterized. Evaluations were undertaken on breast cancer MDA-MB-435S cells and MDA-MB-435S xenografts nude mice. The liposomes were ∼100 nm in size with a narrow polydispersity index. In vitro results showed that the OCT-modified daunorubicin plus dihydroartemisinin liposomes could enhance cytotoxicity and cellular uptake by OCT-SSTRs (somatostatin receptors)-mediated active targeting, block on tumor cell wound healing and migration by incorporating dihydroartemisinin. The action mechanism might be related to regulations on E-cadherin, α5β1-integrin, TGF-β1, VEGF and MMP2/9 in breast cancer cells. In vivo, the liposomes displayed a prolonged circulating time, more accumulation in tumor location, and a robust overall antitumor efficacy with no obvious toxicity at the test dose in MDA-MB-435S xenograft mice. In conclusion, the OCT-modified daunorubicin plus dihydroartemisinin liposomes could prevent breast cancer invasion, hence providing a possible strategy for treatment of metastatic breast cancer.
TL;DR: Male, higher aspartate aminotransferase and direct bilirubin, and lower albumin were significantly associated with an increased risk of death/liver transplantation in TCM-ILI patients.
Abstract: Backgrounds: Traditional Chinese medicine (TCM) is becoming increasingly popular and related adverse events are often ignored or underestimated.Aims: This systematic review aimed to evaluate the clinical characteristics and outcomes of TCM-induced liver injury (TCM-ILI) and to estimate the proportion of TCM-ILI in all drug-induced liver injuries (DILI).Methods: China National Knowledge Infrastructure, Wanfang, VIP, PubMed, and Embase databases were searched. Demographic, clinical, and survival data were extracted and pooled. Factors associated with worse outcomes were calculated. For the proportion meta-analyses, the data were pooled by using a random-effects model.Results: Overall, 21,027 articles were retrieved, of which 625 were finally included. There was a predominance of female and older patients. The proportion of liver transplantation was 2.18% (7/321). The mortality was 4.67% (15/321). Male, higher aspartate aminotransferase and direct bilirubin, and lower albumin were significantly assoc...
TL;DR: It is concluded that miR-142-3p may act as a tumor suppressor in CRC and may serve as a tool for miRNA-based CRC therapy.
Abstract: Background/aims Deregulation of microRNAs (miRNAs) has been associated with a variety of cancers, including colorectal cancer (CRC). Here, we investigated anomalous miR-142-3p expression and its possible functional consequences in primary CRC samples. Methods The expression of miR-142-3p was measured by quantitative RT-PCR in 116 primary CRC tissues and adjacent non-tumor tissues. The effect of miR-142-3p up- or down-regulation in CRC-derived cells was evaluated in vitro by cell viability and colony formation assays and in vivo by growth assays in xenografted nude mice. Results Using quantitative RT-PCR, we found that miR-142-3p was down-regulated in 78.4 % (91/116) of the primary CRC tissues tested when compared to the adjacent non-tumor tissues. We also found that the miR-142-3p mimic reduced in vitro cell viability and colony formation by inducing cell cycle arrest in CRC-derived cells, and inhibited in vivo tumor cell growth in xenografted nude mice. Inversely, we found that the miR-142-3p inhibitor increased the viability and colony forming capacity of CRC-derived cells and tumor cell growth in xenografted nude mice. In addition, we identified CDK4 as a potential target of miR-142-3p by predictions and dual-luciferase reporter assays. Concordantly, we found that miR-142-3p mimics and inhibitors could decrease and increase CDK4 protein levels in CRC-derived cells, respectively. Conclusion From our results we conclude that miR-142-3p may act as a tumor suppressor in CRC and may serve as a tool for miRNA-based CRC therapy.
TL;DR: P pH-sensitive polymeric micelles could be used as potential anti-cancer drug carriers for cancer chemotherapy with controlled release and had negligible cytotoxicity, MTT assay showed.
Abstract: In the present study, a novel pH-responsive amphiphilic copolymer, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)] conjugated poly(β-amino esters) (DSPE-b-PEG-b-PAE...
TL;DR: Three new compounds, isolated from the Portulaca oleracea L. for the first time, were identified and their structures were elucidated using spectroscopic methods, including one- and two-dimensional nuclear magnetic resonance, high-resolution electrospray ionization time-of-flight mass spectrometry and circular dichroism spectromaetry.
TL;DR: It is suggested that 6-Gin attenuates arteriosclerosis in ApoE−/− mice exposed to CMS and HFD, and it may be a potential therapeutic agent for the treatment of atherosclerosis.
Abstract: Chronic mild stress (CMS) has been demonstrated to contribute to atherosclerosis. 6-gingerol (6-Gin), a phenolic component of ginger (Zingiber officinale), has been shown to exert numerous pharmacological properties, such as anti-inflammatory and cardioprotective effects. Here we investigated the role of CMS in the development of atherosclerosis in high-fat diet (HFD)-fed ApoE−/− mice and evaluated the potential therapeutic effects of 6-Gin. Mice were exposed to CMS for 20 weeks, at week 5, they were fed with a high-fat diet (HFD), then received 6-Gin (20 mg/kg/day, intragastrically) treatment. Antiatherosclerotic simvastatin (Sim) and antidepressant lorazepam (Lor) were used for positive drugs. The behavioral and atherosclerotic changes, plasma lipid profiles as well as inflammatory cytokine levels were measured. Our results showed that CMS-exposed mice exhibited reduced body weight gain, sucrose preference and locomotor activity, which are representative of some of the core symptoms of depression. Furthermore, CMS challenge aggravated atherosclerotic lesions, as indicated by increased plaque formation, elevation of plasma total cholesterol, triglyceride, low-density lipoprotein cholesterin, and proinflammatory cytokines including TNF-α, IL-1β, and IL-6. In addition, the expression levels of phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK), acetyl-CoA carboxylase (ACC), hHMG-CoA reductase (HMGCR), fatty acid synthase (FAS), sterol regulatory element binding protein (SREBP)-1 and SREBP-2 in the liver tissues were altered after CMS exposure. 6-Gin not only improved the behavioral changes, but also alleviated atherosclerotic lesions, and reversed the expression levels of lipid profiles and inflammatory cytokines in stressed mice. Moreover, the antiatherosclerotic effects of 6-Gin is mediated in part by the AMPK signaling pathway, which is closely associated with cholesterol synthesis and lipid accumulation. Together, these results suggest that 6-Gin attenuates arteriosclerosis in ApoE−/− mice exposed to CMS and HFD, and it may be a potential therapeutic agent for the treatment of atherosclerosis.
TL;DR: A hollow MOF with an excellent morphology was successfully fabricated and increased the drug loading capacity, achieved a more ideal sustained-release effect, improved the treatment efficiency of the hydrophobic Chinese medicine component, and provided a relatively efficient drug loading material.
TL;DR: Rhein is a potential cancer treatment agent involved in the activation, proliferation, invasion, and migration of cancer cells, and frequently dysregulated in cancer.
Abstract: Background Rhein (1,8-dihydroxy-3-carboxyanthraquinone) is a monomer of anthraquinone derivatives mainly found in Polygonaceae plants such as Rhubarb, and Cuspidatum, widely used in the traditional Chinese medicine with many pharmacological activities, such as antitumor, anti-inflammatory and antifibrotic effects, and regulation of glucose and lipid metabolism. Objective To conclude the role of Rhein in cancer control and its mechanisms for its futher deep research and potential clinical application. Method All kinds of reports previously related to Rhein from PubMed datebase were collected, integrated and analyzed. Results Rhein could control many cancer cells by regulating their proliferation and apoptosis, invasion and migration, especially intrinsic and extrinsic apoptosis pathways induced by Rhein plays the core role in cancer control. For good inhibitory role in NF-κB pathway, the Ras/Raf/MEK (MAPK)/ERK and PTEN/PI3K/AKT/mTOR pathways are other two key pathways regulated by Rhein with its role in antiphosphorylation of ERK, PI3K and AKT to control many cancers' development which frequently dysregulated in cancer, involved in the activation, proliferation, invasion, and migration of cancer cells. Conclusion Rhein is a potential cancer treatment agent.
TL;DR: The combination of miR-128 with TRAIL may represent a novel approach for the treatment of CRC by reducing the resistance of colorectal cancer cells to TRAIL.
Abstract: Background/aims Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an ideal anti-tumor drug because it exhibits selective cytotoxicity against cancer cells. However, certain cancer cells are resistant to TRAIL, and the potential mechanisms are still unclear. The aim of this study was to reduce the resistance of colorectal cancer (CRC) cells to TRAIL. Methods Quantitative real-time PCR analysis was performed to detect the expression of microRNA-128 (miR-128) in tissues from patients with CRC and CRC cell lines. MTT assays were used to evaluate the effect of miR-128 on TRAIL-induced cytotoxicity against CRC cell lines. The distribution of death receptor 5 (DR5) and the production of reactive oxygen species (ROS) were detected by flow cytometry analysis. Western blot, flow cytometry, and luciferase reporter assays were performed to evaluate the potential mechanism and pathway of miR-128-promoted apoptosis in TRAIL-treated CRC cells. Results MiR-128 expression was downregulated in tumor tissues from patients with CRC as well as in CRC cell lines in vitro. The enforced expression of miR-128 sensitized CRC cells to TRAIL-induced cytotoxicity by inducing apoptosis. Mechanistically, bioinformatics, western blot analysis, and luciferase reporter assays showed that miR-128 directly targeted sirtuin 1 (SIRT1) in CRC cells. miR-128 overexpression suppressed SIRT1 expression, which promoted the production of ROS in TRAIL-treated CRC cells. This increase of ROS subsequently induced DR5 expression, and thus increased TRAIL-induced apoptosis in CRC cells. Conclusion The combination of miR-128 with TRAIL may represent a novel approach for the treatment of CRC.
Harvard University1, University of Eastern Piedmont2, French Institute of Health and Medical Research3, University of Cagliari4, Catholic University of the Sacred Heart5, Sapienza University of Rome6, Innsbruck Medical University7, Dresden University of Technology8, University of Pavia9, Liaoning University of Traditional Chinese Medicine10, University of Amsterdam11
TL;DR: A new patient‐centered prognostic index for patients with advanced MDS is developed by including self‐reported fatigue severity into a well‐established clinical risk classification: the International Prognostic Scoring System (IPSS).
Abstract: Background Current prognostic systems for myelodysplastic syndromes (MDS) are based on clinical, pathologic, and laboratory indicators. The objective of the current study was to develop a new patient-centered prognostic index for patients with advanced MDS by including self-reported fatigue severity into a well-established clinical risk classification: the International Prognostic Scoring System (IPSS). Methods A total of 469 patients with advanced (ie, IPSS intermediate-2 or high-risk) MDS were analyzed. Untreated patients (280 patients) were recruited into an international prospective cohort observational study to create the index. The index then was applied to an independent cohort including pretreated patients with MDS from the Dana-Farber Cancer Institute in Boston, Massachusetts (189 patients). At baseline, patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Results A new prognostic index was developed: the FA-IPSS(h), in which FA stands for fatigue and h for higher-risk. This new risk classification enabled the authors to distinguish 3 subgroups of patients with distinct survival outcomes (ie, risk-1, risk-2, and risk-3). Patients classified as FA-IPSS(h) risk-1 had a median overall survival (OS) of 23 months (95% confidence interval [95% CI], 19-29 months), whereas those with risk-2 had a median OS of 16 months (95% CI, 12-17 months) and those with risk-3 had a median OS of 10 months (95% CI, 4-13 months). The predictive accuracy of this new index was higher than that of the IPSS alone in both the development cohort as well as in the independent cohort including pretreated patients. Conclusions The FA-IPSS(h) is a novel patient-centered prognostic index that includes patients' self-reported fatigue severity. The authors believe its use might enhance physicians' ability to predict survival more accurately in patients with advanced MDS. Cancer 2018;124:1251-9. © 2017 American Cancer Society.
TL;DR: The findings support that Ost is a potential drug for treating MBI due to its neuronal restoration, and demonstrate that osthole (Ost), a natural coumarin derivative, was capable of promoting the proliferation of endogenous NSCs and improving neuronal restoration.
Abstract: Mechanical brain injury (MBI) is a common neurotrosis disorder of the central nervous system (CNS), which has a higher mortality and disability. In the case of MBI, neurons death leads to loss of nerve function. To date, there was no satisfactory way to restore neural deficits caused by MBI. Endogenous neural stem cells (NSCs) can proliferate, differentiate and migrate to the lesions after brain injury, to replace and repair the damaged neural cells in the subventricular zone (SVZ), hippocampus and the regions of brain injury. In the present study, we first prepared a mouse model of cortical stab wound brain injury. Using the immunohistochemical and hematoxylin-eosin (H&E) staining method, we demonstrated that osthole (Ost), a natural coumarin derivative, was capable of promoting the proliferation of endogenous NSCs and improving neuronal restoration. Then, using the Morris water maze (MWM) test, we revealed that Ost significantly improved the learning and memory function in the MBI mice, increased the number of neurons in the regions of brain injury, hippocampus DG and CA3 regions. Additionally, we found that Ost up-regulated the expression of self-renewal genes Notch 1 and Hes 1. However, when Notch activity was blocked by the γ-secretase inhibitor DAPT, the expression of Notch 1 and Hes 1 mRNA was down-regulated, augmentation of NICD and Hes 1 protein was ameliorated, the proliferation-inducing effect of Ost was abolished. These results suggested that the effects of Ost were at least in part mediated by activation of Notch signaling pathway. Our findings support that Ost is a potential drug for treating MBI due to its neuronal restoration.
TL;DR: The prepared HA-modified daunorubicin plus HNK cationic liposomes may serve as a promising therapeutic strategy for the treatment of breast cancer.
Abstract: Background: Breast cancer is an alarming global public health problem and a main cause of cancer-related death in women. Systemic chemotherapy is the most widely used treatment for breast c...
TL;DR: A novel isoindole alkaloid named oleraisoindole, together with six known compounds, was isolated from Portulaca oleracea L. and was shown to inhibit NO production in RAW 264.7 cells induced by LPS.
TL;DR: Allicin provided cardioprotection for CH rats by improving the function of CMECs through increasing the expression of PECAM-1, and the role of allicin was disappear after PECam-1 was silenced.
TL;DR: Oleraciamide D (1) showed cytotoxicity against SH-SY5Y cells when concentration at 50 uM by CCK-8 method, and the structure of the new alkaloid was elucidated via UHPLC-ESI-Q-TOF/MS, 1D N MR and 2D NMR.
TL;DR: The results demonstrated that the functional docetaxel nanomicelles could transport across the BBB, enhance the cellular uptake, target to the mitochondria, induce the apoptosis, increase the cytotoxicity in the brain glioma cells, and extend survival span of the brainglioma-bearing mice.
Abstract: The efficacy of anticancer drugs is rather limited in the treatment of brain glioma due to the hindrance of the blood-brain barrier (BBB). Herein, we reported an easy formulation of functional docetaxel nanomicelles for the treatment of brain glioma using a graft copolymer soluplus as basic material through dual-modifications with a glucose-lipid derivative and a dequalinium-lipid derivative. The studies were performed on brain glioma U87MG cells, in vitro BBB models and brain glioma-bearing nude mice. The functional docetaxel nanomicelles were approximately 100 nm. The results demonstrated that the functional docetaxel nanomicelles could transport across the BBB, enhance the cellular uptake, target to the mitochondria, induce the apoptosis, increase the cytotoxicity in the brain glioma cells, and extend survival span of the brain glioma-bearing mice. The action mechanisms were associated with dual-modifications by the glucose-lipid derivative and the dequalinium-lipid derivative, both of which are beneficial for the transport across the BBB. Furthermore, the modification with dequalinium-lipid derivative was able to target to the brain glioma cells and to the mitochondria. In conclusion, the functional docetaxel nanomicelles would be a promising formulation for the treatment of brain glioma, deserving further development for clinical trials.
TL;DR: The structural change of microemulsions in simulated gastrointestinal conditions is studied by SAXS and FRET, and the appearance and disappearance of the liquid crystalline phases and micelles are monitored.
TL;DR: The prepared MX-BSA-NS significantly increased the inflammation-targeting properties and bioavailability of MX, suggesting its potential as a promising formulation for the targeted drug delivery of MX in future clinical applications.
Abstract: Background The objective of this study was to develop a more bio-available and safe nanosuspension of meloxicam (MX), which could dramatically improve inflammation targeting. Methods and results MX-loaded bovine serum albumin (BSA) nanosuspensions were prepared using acid-base neutralization in aqueous solution and the prepared nanosuspensions were characterized. The results obtained showed that the prepared nanosuspensions had a narrow size distribution with a mean particle size of 78.67±0.22 nm, a polydispersity index of 0.133±0.01, and a zeta potential of -11.87±0.91 mV. The prepared MX nanosuspensions were spherically wrapped by BSA with a smooth surface as shown by transmission electron microscopy. Stability studies showed that the nanosuspensions were physically stable at 4°C with a shelf life of at least 6 months. In the in vitro dissolution test, the MX-loaded BSA nanosuspension (MX-BSA-NS) exhibited sustained release. In addition, an in vivo pharmacokinetic study in rats following intravenous injection showed that the half-life (t1/2), mean residence time (MRT), and area under the concentration-time curve (AUC0-∞) of MX-BSA-NS was increased by 169.83%, 150.13%, and 148.80%, respectively, in comparison with MX conventional solution (MX solution). Furthermore, results from inflammation targeting studies showed that the concentration of MX increased significantly in inflamed tissues but was reduced in normal tissues compared with the MX solution group after injection of MX-BSA-NS. Conclusion The prepared MX-BSA-NS significantly increased the inflammation-targeting properties and bioavailability of MX, suggesting its potential as a promising formulation for the targeted drug delivery of MX in future clinical applications.
TL;DR: Head and neck tuberculosis should always be considered during a differential diagnosis for lesions in the head and neck region, according to a HIV test, and 40 patients had comorbidities with different types of tumors.
Abstract: Tuberculosis (TB) is an infectious disease and major health concern. Head and neck tuberculosis (HNTB) is relatively rare, but can arise in many regions, including the lymph nodes, larynx, oral cavity and pharynx. We retrospectively reviewed the clinical records of 60 patients diagnosed with HNTB in our department between March 2005 and January 2016. A review and summary of previous HNTB articles published in PubMed since 1885 was also performed. The subjects consisted of 17 males and 43 females, and the average age of patients was 45 ± 14.67 years. The major clinical presentation was a lump or swelling, followed by an oral ulcer and skin fistula. The most common site of tuberculosis was in the cervical lymph node. Three patients also suffered from a malignant tumor in the head and neck region. A total of 980 papers involving 5881 patients were included in our literature review. The included subjects ranged in age from 15 months to 100 years with a male-to-female ratio of 1.5:1. The larynx (38.92%), cervical lymph nodes (38.28%) and oral cavity (9.92%) were the three most common development sites. 465 patients were positive according to a HIV test, and 40 patients had comorbidities with different types of tumors. Head and neck tuberculosis should always be considered during a differential diagnosis for lesions in the head and neck region. Early diagnosis and treatment can greatly enhance the therapeutic effect and patients' quality of life.
TL;DR: A potential mechanism underlying the protective role of baicalin in the in vitro model of AS is suggested and these results may be used to develop novel therapeutic approaches for the affected patients.
Abstract: Atherosclerosis (AS) is a systemic disease associated with lipid metabolic disorders and abnormal proliferation of smooth muscle cells. Baicalin is a flavonoid compound isolated from the dry roots of Scutellaria baicalensis Georgi and exerts anti‑proliferative effects in various types of cells. However, the effect of baicalin on AS remains unclear. In the present study, serum samples were collected from patients with AS and an in vitro model of AS was established using oxidized low‑density lipoprotein (ox‑LDL)‑treated human aorta vascular smooth muscle cells (HA‑VSMCs). The siRNA transfection and overexpression efficiency of endogenous maternally expressed gene 3 (MEG3) and the expression level of MEG3 were analyzed by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The effects of alterations in expression levels of MEG3 were assessed by MTT assay, bromodeoxyuridine incorporation assay, 5‑ethynyl‑2'‑deoxyuridine staining, wound healing assay, immunofluorescence and western blotting in HA‑VSMCs. qPCR indicated that the expression of MEG3 was reduced in serum samples from patients with AS and ox‑LDL‑treated HA‑VSMCs, compared with serum samples from healthy patients and untreated HA‑VSMCs, respectively. Further experiments indicated that ox‑LDL‑induced decrease of MEG3 expression was reversed by treatment with baicalin in a concentration‑dependent manner. Following treatment with ox‑LDL, decreased expression of MEG3 promoted proliferation and migration, and suppressed apoptosis in HA‑VSMCs. Furthermore, treatment with baicalin reversed these effects on proliferation and apoptosis in ox‑LDL‑treated HA‑VSMCs. The current study indicated that downregulated expression of MEG3 increased cell cycle‑associated protein expression. However, treatment with baicalin inhibited the expression of cell‑cycle associated proteins in HA‑VSMCs with MEG3 knockdown. In addition, baicalin activated the p53 signaling pathway and promoted the expression and transport of p53 from the cytoplasm to nucleus following MEG3 knockdown in ox‑LDL‑treated HA‑VSMCs. Baicalin inhibited proliferation and promoted apoptosis by regulating the expression of MEG3/p53, indicating that baicalin may serve a role in AS by activating the MEG3/p53 signaling pathway. The present study suggested a potential mechanism underlying the protective role of baicalin in the in vitro model of AS, and these results may be used to develop novel therapeutic approaches for the affected patients.