Showing papers by "Liaoning University of Traditional Chinese Medicine published in 2017"
TL;DR: An exploration of dual-stimuli responsive as well as real-time imaging targeted drug delivery system based on HMSN and the prepared HMSN-SS-CDPEI@HA could be a promising platform for cancer therapy.
91 citations
TL;DR: In vivo results demonstrated that TF modified vincristine plus tetrandrine liposomes could significantly prolong the circulation time, obviously accumulate in brain tumor location, thus leading to a robust anticancer efficacy in glioma‐bearing mice.
61 citations
TL;DR: Oxymatrine alleviated EMT induced in colorectal cancer via inhibition of TGF-β1/Smad signaling pathway activation by reducing P38-dependent increased expression of PAI-1, which could be a novel therapeutic agent for coloreCTal cancer.
Abstract: Transforming growth factor-β1 (TGF-β1) signaling has been shown to play a critical role in the development of epithelial-mesenchymal transition (EMT). PAI-1 is one of the most important target genes in the TGF-β/Smad signaling pathway, which can hinder the degradation of ECM composition and may promote cell invasion and migration. Oxymatrine (OM) is an alkaloid extracted from the Chinese herb Sophora flavescens Ait and has been demonstrated to inhibit the growth of various types of cancer cells including colorectal cancer. However, the anticancer effect of OM in colorectal cancer remains unclear. In the present study, we detected the expression of E-cadherin, α-SMA, FN, TGF-β1, PAI-1, Smad4, pP38 and pSmad2 in FHC, RKO and OM-treated RKO cells. We also detected pSmad2 and PAI-1 in RKO cells following the addition of SB203580 (a p38 MAPK inhibitor). The results showed that E-cadherin expression in RKO cells was significantly decreased, while PAI-1, TGF-β1, α-SMA, FN, Smad4, pSmad2 and pP38 expression levels were significantly increased in the RKO cells compared to levels in the FHC cells, which was almost completely reversed by OM. OM alleviated EMT induced in colorectal cancer via inhibition of TGF-β1/Smad signaling pathway activation by reducing P38-dependent increased expression of PAI-1. Hence, OM could be a novel therapeutic agent for colorectal cancer.
61 citations
TL;DR: In vivo and in vitro, AS-IV treatment increased PPARγ and BACE1 expression and reduced neuritic plaque formation and Aβ levels in the brains of APP/PS1 mice, indicating thatAS-IV may be a promising agent for modulating Aβ-related pathology in AD.
Abstract: A number of epidemiological studies have established a link between Alzheimer’s disease (AD) and diabetes mellitus (DM). So, nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) plays an important role in the treatment of AD. However, current PPARγ-targeting drugs such as thiazolidinediones (TZDs) are associated with undesirable side effects. We identified herbal extract with a small molecular, astragaloside IV (AS-IV), as a selective PPARγ natural agonist in nervous cells by developing a PPAR-PPRE pathway regulatory system. Cultured SH-SY5Y cells transfected with pEGFP-N1-BACE1 were treated with AS-IV for 24 h or AS-IV plus the PPAR-γ antagonist GW9662 in vitro. APP/PS1 mice were intragastrically treated with AS-IV or AS-IV plus the GW9662 every 48 h for 3 months. Immunofluorescence, western blotting, and real-time PCR were used to examine the expression of PPARγ and BACE1. Immunohistochemical staining was performed to analyze the distribution of Aβ plaques in the APP/PS1 mouse brain. The levels of Aβ were determined using ELISA kits. AS-IV was shown to be a PPARγ agonist by establishing a high-throughput screening model for PPARγ agonists. The results showed that AS-IV treatment increased activity of PPARγ and inhibited BACE1 in vitro. As a result, Aβ levels decreased significantly. GW9662, which is a PPARγ antagonist, significantly blocked the beneficial role of AS-IV. In vivo, AS-IV treatment increased PPARγ and BACE1 expression and reduced neuritic plaque formation and Aβ levels in the brains of APP/PS1 mice. These effects of AS-IV could be effectively inhibited by GW9662. These results indicate that AS-IV may be a natural PPARγ agonist that suppressed activity of BACE1 and ultimately attenuates generation of Aβ. Therefore, AS-IV may be a promising agent for modulating Aβ-related pathology in AD.
60 citations
TL;DR: The findings suggest that ginsenoside Rb1 might restore cardiac/mitochondrial function, increase glucose uptake and protect against cardiac remodeling via the TGF-β1/Smad, ERK and Akt signaling pathways.
Abstract: We investigated the effect of ginsenoside Rb1 on cardiac function and remodeling in heart failure (HF). Four weeks after HF induction, the rats were administrated with ginsenoside Rb1 (35 and 70 mg/kg) and losartan (4.5 mg/kg) for 8 weeks. Losartan was used as a positive control. Cardiac function was assessed by measuring hemodynamic parameters. Histological changes were analyzed by HE and Masson's trichrome staining. Cardiac hypertrophy, fibrosis, mitochondrial membrane potential and glucose transporter type 4 (GLUT4) levels were evaluated. In the present study, high dose of (H-) ginsenoside Rb1 decreased heart rate, improved cardiac function and alleviated histological changes induced by HF. H-ginsenoside Rb1 attenuated cardiac hypertrophy and myocardial fibrosis by decreasing left ventricular (LV) weight/heart weight ratio and cardiomyocyte cross-sectional area and reducing the levels of atrial natriuretic factor (ANF), β-myosin heavy chain (β-MHC), periostin, collagen I, Angiotensin II (Ang II), Angiotensin converting enzyme (ACE) and Ang II type 1 (AT1) receptor. Moreover, H-ginsenoside Rb1 decreased mitochondrial membrane potential and enhanced the translocation of GLUT4 to plasma membrane. The TGF-β1/Smad and ERK signaling pathways were inhibited and the Akt pathway was activated. These findings suggest that ginsenoside Rb1 might restore cardiac/mitochondrial function, increase glucose uptake and protect against cardiac remodeling via the TGF-β1/Smad, ERK and Akt signaling pathways.
59 citations
TL;DR: The results suggest that cotreatment with BZYQD and cisplatin may represent a novel approach in treatment for NSCLC and thus offer a new target for chemotherapy.
Abstract: Cisplatin is one of the most active cytotoxic agents for non-small cell lung cancer (NSCLC) treatment. However, the development of cisplatin resistance is common. Bu-Zhong-Yi-Qi decoction (BZYQD), a Chinese traditional herbal medicine, is widely used for the enhancement of antitumor effect in other medications. In this study, we evaluated the effect and drug-resistance reversal mechanism of BZYQD combined with cisplatin on cisplatin-resistant A549/DDP cells. Our results showed that BZYQD exhibited direct cytotoxic and chemosensitizing effects. Cotreatment with BZYQD and cisplatin induced intrinsic apoptotic pathways which were measured by condensed nuclear chromatin, Annexin V/PI apoptosis assay, and apoptosis related proteins expression. In addition, cotreatment with BZYQD and cisplatin also activated autophagy, as indicated by an increase in LC3 puncta, classical autophagosomes and/or autolysosomes, and an accumulation of LC3-II and ATG7 protein. Finally, cotreatment with BZYQD and cisplatin resulted in the generation of ROS and scavenging ROS by NAC almost completely suppressing cell death. These results suggest that cotreatment with BZYQD and cisplatin might reverse cisplatin resistance by inducing ROS accumulation, which activates apoptosis and autophagy by oxidative stress. The combination of BZYQD and cisplatin may represent a novel approach in treatment for NSCLC and thus offer a new target for chemotherapy.
55 citations
TL;DR: In vivo results exhibited that multifunctional targeting epirubicin liposomes could accumulate selectively in tumor site and display an obvious antitumor efficacy, and no significant toxicity of blood system and major organs was observed at a test dose.
Abstract: Chemotherapy for aggressive non-small-cell lung cancer (NSCLC) usually results in a poor prognosis due to tumor metastasis, vasculogenic mimicry (VM) channels, limited killing of tumor cells, and severe systemic toxicity. Herein, we developed a kind of multifunctional targeting epirubicin liposomes to enhance antitumor efficacy for NSCLC. In the liposomes, octreotide was modified on liposomal surface for obtaining a receptor-mediated targeting effect, and honokiol was incorporated into the lipid bilayer for inhibiting tumor metastasis and eliminating VM channels. In vitro cellular assays showed that multifunctional targeting epirubicin liposomes not only exhibited the strongest cytotoxic effect on Lewis lung tumor cells but also showed the most efficient inhibition on VM channels. Action mechanism studies showed that multifunctional targeting epirubicin liposomes could downregulate PI3K, MMP-2, MMP-9, VE-Cadherin, and FAK and activate apoptotic enzyme caspase 3. In vivo results exhibited that multifunctional targeting epirubicin liposomes could accumulate selectively in tumor site and display an obvious antitumor efficacy. In addition, no significant toxicity of blood system and major organs was observed at a test dose. Therefore, multifunctional targeting epirubicin liposomes may provide a safe and efficient therapy strategy for NSCLC.
48 citations
TL;DR: TEPT could promote wound shrinkage, improve healing rate and promote healing of infectious wounds in rats and may be due to antibacterial activities and NIH3T3 cell pro-proliferative effect of the tannins compounds, indicating that TEPT can be used as efficient treatment in traumatic injury.
43 citations
TL;DR: In this review, the new emerging target descriptors and cross‐term descriptors not only significantly increased the performance of PCM modelling but also expanded its application scope from traditional protein‐ligand interaction to more abundant interactions, including protein‐peptide, protein‐DNA and even protein‐protein interactions.
Abstract: As an extension of the conventional quantitative structure activity relationship models, proteochemometric (PCM) modelling is a computational method that can predict the bioactivity relations between multiple ligands and multiple targets. Traditional PCM modelling includes three essential elements: descriptors (including target descriptors, ligand descriptors and cross-term descriptors), bioactivity data and appropriate learning functions that link the descriptors to the bioactivity data. Since its appearance, PCM modelling has developed rapidly over the past decade by taking advantage of the progress of different descriptors and machine learning techniques, along with the increasing amounts of available bioactivity data. Specifically, the new emerging target descriptors and cross-term descriptors not only significantly increased the performance of PCM modelling but also expanded its application scope from traditional protein-ligand interaction to more abundant interactions, including protein-peptide, protein-DNA and even protein-protein interactions. In this review, target descriptors and cross-term descriptors, as well as the corresponding application scope, are intensively summarized. Additionally, we look forward to seeing PCM modelling extend into new application scopes, such as Target-Catalyst-Ligand systems, with the further development of descriptors, machine learning techniques and increasing amounts of available bioactivity data.
39 citations
TL;DR: In a test of tumor-bearing mice, the His-AAP PTX micelles significantly inhibited tumor growth and showed that his-A AP PTX mouselles are a highly promising therapeutic system for anticancer therapy.
Abstract: The study was aimed to design a novel pH-sensitive carrier to deliver antitumor drugs to increase treatment efficiency. Histidine (His)was used to modify auricularia auricular polysaccharide (AAP) by esterification. Proton nuclear magnetic resonance spectrometry was developed to characterize the His-AAP carrier and the His-AAP Paclitaxel (PTX) micelles were prepared by self-assembled organic solvent evaporation. The formation of His-AAP PTX micelles was confirmed by dynamic light-scattering, transmission electron microscopy and high performance liquid chromatography. It was found that the His-AAP PTX micelles possessed a spherical morphology with an average diameter of 157.2 nm and an 80.3% PTX encapsulation efficiency. In vitro release at pH 7.4, 6.5, 5.0 reached 70%, 71%, and 88%, respectively. The cell viability assay and confocal laser scanning microscope were used to evaluate the cytotoxicity and cell uptake of the His-AAP PTX micelles. Compared with Taxol, the IC50 of the His-AAP PTX micelles were lower after incubating for 24 h, 48 h, or 72 h (0.216 versus 0.199, 0.065 versus 0.060, and 0.023 versus 0.005, respectively). In a test of tumor-bearing mice, the His-AAP PTX micelles significantly inhibited tumor growth. These results showed that His-AAP PTX micelles are a highly promising therapeutic system for anticancer therapy.
38 citations
TL;DR: Naringin attenuates inflammatory response, oxidative stress and NF-κB activation in experimental models of DR, and alleviated DR symptoms as evidenced by the increased retinal ganglion cells and decreased GFAP level in rat retina.
Abstract: Objective(s): Naringin, an essential flavonoid, inhibits inflammatory response and oxidative stress in diabetes. However, whether naringin has beneficial effects on diabetic retinopathy (DR) remains unknown. Materials and Methods: Streptozotocin (STZ, 65 mg/kg) was intraperitoneally injected into male rats (8 weeks old weighting 200-250 g) to establish diabetic model, then naringin (20, 40 or 80 mg/kg/day) was intraperitoneally injected into the diabetic rats for twelve weeks. Glial fibrillary acidic protein (GFAP) level, thickness of ganglion cell layer (GCL) and ganglion cell counts were assessed in diabetic retina in vivo. Naringin (50 μM) that significantly inhibited high glucose (HG, 25 mM)-induced cell proliferation was used to treat rat Muller cell line (rMC1) in vitro. Inflammatory response, oxidative stress and activation of nuclear factor kappa B (NF-κB) p65 were evaluated in retina in vivo and in rMC1 cells in vitro. Results: Naringin alleviated DR symptoms as evidenced by the increased retinal ganglion cells and decreased GFAP level in rat retina. Naringin exhibited anti-inflammatory and antioxidative effects as confirmed by the down-regulated pro-inflammatory cytokines, tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), and the up-regulated antioxidants, glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) in DR rats. Moreover, we found that naringin inhibited HG-induced proliferation, abnormal inflammatory response and oxidative stress in rMC1 cells. In addition, the enhanced nuclear translocation of NF-κB p65 in diabetic rat retina and HG-induced rMC1 cells was suppressed by naringin. Conclusion: Naringin attenuates inflammatory response, oxidative stress and NF-κB activation in experimental models of DR.
TL;DR: The results indicate that SCU protects against NAFLD in rats via attenuation of oxidative stress, and suggest that breviscapine may be a potentially useful therapeutic strategy forNAFLD and hyperlipidemia.
Abstract: BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a condition characterized by excessive fat accumulation in the form of triglycerides. The incidence of NAFLD and hyperlipidemia, with their associated risks of end-stage liver and cardiovascular diseases, is increasing rapidly. This study aimed to investigate the effects of scutellarin on the experimental NAFLD in high-fat diet fed and chronic stress rats, and its possible mechanism. MATERIAL AND METHODS Sprague-Dawley rats were fed with high-fat diet and subjected to chronic stress for 12 weeks, and administered orally with scutellarin for 4 weeks (n=8), and then blood and livers were harvested for analyzing. Enzyme activity assay, immunofluorescence, Western blot, and quantitative RT-PCR were performed to analyze the factors of the oxidant/antioxidant system and pathway. RESULTS After the high-fat diet and chronic stress administration for 12 weeks, serum and liver lipid metabolism of treatment groups with the different doses of SCU effectively improved and the degree of oxidative damage reduced. Using Western blot assay and immunofluorescence (IF) staining assay, Nrf2, HO-1, and PI3K, and AKT proteins significantly increased after SCU treatment for 4 weeks (P 0.05). These results indicate that SCU protects against NAFLD in rats via attenuation of oxidative stress. CONCLUSIONS The antioxidant effects of SCU on NAFLD are possibly dependent on PI3K/AKT activation with subsequent Nrf2 nuclear translocation, which increases expression of HO-1 and NQO1. We therefore suggest that breviscapine may be a potentially useful therapeutic strategy for NAFLD and hyperlipidemia.
TL;DR: A novel alkaloid, with six known compounds, hydroxydihydrobovolide (2), uracil (3), catechol (4), 4-aminophenol (5), vanillic acid (6) as well as 3-hydroxypyridine (7), were isolated from Portulaca oleracea L.
TL;DR: Evidence of the neurogenesis effects and neurobiological mechanisms of Ost against AD are provided, suggesting that Ost is a promising drug for treatment of AD or other neurodegenerative diseases.
Abstract: Alzheimer's disease (AD) is the most serious neurodegenerative disease worldwide and is characterized by progressive cognitive impairment and multiple neurological changes, including neuronal loss in the brain. However, there are no available drugs to delay or cure this disease. Consequently, neuronal replacement therapy may be a strategy to treat AD. Osthole (Ost), a natural coumarin derivative, crosses the blood-brain barrier and exerts strong neuroprotective effects against AD in vitro and in vivo. Recently, microRNAs (miRNAs) have demonstrated a crucial role in pathological processes of AD, implying that targeting miRNAs could be a therapeutic approach to AD. In the present study, we investigated whether Ost could enhance cell viability and prevent cell death in amyloid precursor protein (APP)-expressing neural stem cells (NSCs) as well as promote APP-expressing NSCs differentiation into more neurons by upregulating microRNA (miR)-9 and inhibiting the Notch signaling pathway in vitro. In addition, Ost treatment in APP/PS1 double transgenic (Tg) mice markedly restored cognitive functions, reduced Aβ plague production and rescued functional impairment of hippocampal neurons. The results of the present study provides evidence of the neurogenesis effects and neurobiological mechanisms of Ost against AD, suggesting that Ost is a promising drug for treatment of AD or other neurodegenerative diseases.
TL;DR: Results indicate that PPIs may be successfully incorporated into the FOLFOX regimen to increase the chemotherapeutic effect for CRC patients.
Abstract: // Xiaoyu Wang 1 , Chun Liu 2 , Jiaqi Wang 3 , Yue Fan 4 , Zhenghua Wang 1 and Yuanyuan Wang 1 1 Third Ward of Oncology Department, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 121001, China 2 Department of Biochemistry, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, 110001, China 3 Traditional Chinese Medicine Department, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 121001, China 4 Jinzhou Medical University, Jinzhou, Liaoning, 121001, China Correspondence to: Jiaqi Wang, email: zyjiaqi@126.com Keywords: PPI, chemosensitization, 5-FU, FOLFOX, capeOx Received: February 10, 2017 Accepted: June 05, 2017 Published: June 16, 2017 ABSTRACT Changes in pH can alter the uptake of chemotherapy drugs. Proton pump inhibitors (PPIs) may therefore increase the chemosensitivity of cancer cells and cytotoxicity of chemotherapeutic drugs by increasing their uptake. We investigated the chemosensitizing potential of PPIs in colorectal cancer (CRC). Our in vitro data show that the PPI pantoprazole increases the chemosensitivity of CRC HT29 and RKO cells to fluorouracil (5-FU). Our in vivo data demonstrate that pantoprazole also increases the ability of 5-FU to inhibit CRC tumor growth in mice. Importantly, a retrospective clinical study of CRC patients receiving the FOLFOX or CapeOx regimen indicates that PPIs increase the chemosensitivity of CRC patients. Patients who received the FOLFOX regimen with a PPI had better overall survival (OS) and progression-free survival (PFS) than patients who did not receive a PPI during FOLFOX chemotherapy. The incidence of nausea and vomiting was also lower in patients receiving a PPI with FOLFOX or CapeOx than in those who did not receive PPI. These results indicate that PPIs may be successfully incorporated into the FOLFOX regimen to increase the chemotherapeutic effect for CRC patients.
TL;DR: In vitro results showed that the targeting liposomes with suitable physicochemical property could enhance the drug transportation acrossing the BBB, inhibit C6 cells invasion and destroy VM channels, and in vivo results displayed the targetingliposomes improved accumulation in brain tumor tissue and exhibited obvious antitumor efficacy.
TL;DR: It is suggested that Ost protects BM-NSCs against oxidative stress injury, and it can be used to improve the inflammatory environment of neurodegenerative diseases so and promote the survival rate of transplanted NSCs.
Abstract: In recent years, neural stem cell (NSC) transplantation has been widely explored as a treatment for neurodegenerative diseases. NSCs are special cells that have some capacity for self-renewal and the potential to differentiate into multiple cell types. However, the inflammatory environment of diseased tissue is not conducive to the survival of transplanted cells. Osthole (Ost) is a principal bioactive component of Fructus Cnidii, Radix Angelicae Pubescentis and other traditional Chinese medicines. Ost has a wide range of pharmacological activities, such as anti-inflammation, immunomodulation, and neuroprotection. In the present study, we assessed the protective effects of Ost on bone marrow-derived-NSCs (BM-NSCs) against injury induced by hydrogen peroxide (H2O2). BM-NSCs were pre-treated with different doses of Ost and treated with H2O2. The cell counting kit-8 (CCK-8) method and lactate dehydrogenase (LDH) leakage assay were used to determine cell viability. Using the TUNEL assay and RT-PCR, we evaluated the effect of Ost on cell apoptosis. The results showed that Ost had protective effects against H2O2-induced cell damage, and the number of apoptotic cells was significantly decreased in the Ost pre-treated groups compared to the H2O2 group. The expression ratio of Bax/Bcl-2 mRNA was also decreased. Furthermore, western blotting was used to analyze levels of proteins related to PI3K/Akt-1 signaling pathway, and results indicated that ost can increase p-Akt and PI3K. Our findings suggested that Ost protects BM-NSCs against oxidative stress injury, and it can be used to improve the inflammatory environment of neurodegenerative diseases so and promote the survival rate of transplanted NSCs.
TL;DR: The mechanism of therapeutic effects of SHHZF on liver cancer by adjusting the activities of PE N-methyl transferase, Lysophospholipase D, methylenetetrahydrofolate reductase and lysophosphlipase was elucidated by the method of metabonomics for the first time.
TL;DR: It was demonstrated that the upregulation of MEG3 significantly increased the transactivation of p53 and induced downstream changes in protein expression, which imply that M EG3 may be a marker for predicting the occurrence and development of osteosarcoma.
Abstract: Osteosarcoma is known as a malignant tumour with a high mortality rate in orthopaedic settings; however, the factors associated with its degree of malignancy and the biological response remains to be elucidated. Although the essential role of the long noncoding RNA (lncRNA) maternally expressed 3 (MEG3) has been recently reported, its biological functions and regulatory mechanism in osteosarcoma cells have not yet been reported. In the present study, reverse transcription-quantitative polymerase chain reaction analysis revealed that the expression of MEG3 in MG63 cells was lower compared with in hFOB1.19 cells. Furthermore, it was observed that overexpressing MEG3 in MG63 cells resulted in a decline in the proliferation and invasion, and a marked increase in apoptosis. Additionally, western blotting was used to detect the changes in expression of p53 and MDM2 proto-oncogene, which may be regulated by MEG3, and proteins that associated with cell proliferation, invasion and apoptosis. It was demonstrated that the upregulation of MEG3 significantly increased the transactivation of p53 and induced downstream changes in protein expression. In conclusion, these experiments have demonstrated that MEG3 serves an essential regulatory role in the biological processes of human osteosarcoma cells, and imply that MEG3 may be a marker for predicting the occurrence and development of osteosarcoma.
TL;DR: The results suggest that TSIIA attenuates oxidative stress by decreasing ROS and MDA production and enhancing the activity of T-SOD and GSH-PX, which may contribute to the inhibition of apoptosis and amelioration of liver steatosis.
Abstract: Oxidative stress is a crucial factor associated with fatty liver disease, which raises the possibility of using antioxidants to improve liver steatosis. Tanshinone IIA (TSIIA) is a traditional Chinese medicine that has been reported to have antioxidant effects in vitro. The present study aimed to investigate whether TSIIA possesses antioxidant effects in vivo and whether TSIIA was able to improve liver steatosis. Hence, the ability of TSIIA to protect rats from liver disease was explored, particularly in regard to antioxidant activity. Rats were fed a high-lipid diet for 90 days, causing severe liver steatosis, both morphologically and biochemically. An increase in reactive oxygen species (ROS) in the liver was exhibited in addition to significantly elevated serum lipids and malondialdehyde (MDA). Furthermore, hepatocyte apoptosis was measured by Hoechst staining, reverse transcription-quantitative polymerase chain reaction and western blot analysis and an increase in hepatocyte apoptosis rate was indicated in mice on a high-fat diet. Following intraperitoneal injection of TSIIA (10 mg/kg/day), liver steatosis was significantly inhibited. In rats receiving TSIIA treatment, less ROS were indicated in the liver and significantly decreased levels of MDA (P<0.05) in serum were exhibited, whereas significantly increased activities of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-PX) were observed (P<0.05 and P<0.01, respectively). In addition, the rate of hepatocyte apoptosis was significantly decreased in the TSIIA group (P<0.01). However, TSIIA elicited no effect on serum lipid profiles. These results suggest that TSIIA attenuates oxidative stress by decreasing ROS and MDA production and enhancing the activity of T-SOD and GSH-PX, which may contribute to the inhibition of apoptosis and amelioration of liver steatosis.
TL;DR: It is suggested that imatinib crosses the blood-testis barrier and reduces sperm density, sperm count, survival rates, and activity in CML-CP patients, but did not affect the structure of reproductive organs or sex hormone levels.
Abstract: Imatinib is a first-line tyrosine kinase inhibitor for treating chronic myelogenous leukaemia (CML) and has greatly improved the prognosis of this disease. An increasing number of CML patients of reproductive age are diagnosed each year, and the impact of imatinib on fertility is a major concern. Providing useful advice to these patients regarding the choice of their therapeutic treatment is very important. This study examined the impact of imatinib on the fertility of male patients with CML in the chronic phase. We performed a study of 48 adult male CML patients in the chronic phase (CML-CP), 50 healthy control subjects, and 10 male patients with infertility. Imatinib levels in semen and plasma were measured using high-performance liquid chromatography/mass spectrometry. We examined the effects of imatinib on sperm parameters and the male reproductive system using a computer-assisted sperm assay and ultrasound, respectively. We analysed sex hormone levels in the sera of CML-CP patients using an enzyme-linked immunosorbent assay. Imatinib levels in semen were comparable to plasma levels in CML-CP patients. CML-CP patients treated with imatinib exhibited reduced sperm density, counts, survival rates, and activity. Ultrasound demonstrated that the shape and size of the testis and epididymis in CML-CP patients undergoing imatinib treatment were normal. However, 19 of these patients exhibited a hydrocele in their tunica vaginalis, with a large dark area of effusion (0.7–2.9 cm in width). Sex hormone levels in the sera of the CML-CP patients were normal. These results suggest that imatinib crosses the blood-testis barrier and reduces sperm density, sperm count, survival rates, and activity in CML-CP patients. However, imatinib did not affect the structure of reproductive organs or sex hormone levels.
TL;DR: The results showed that all these compounds have definite protective effect on MPP+-induced SH-SY5Y cells.
TL;DR: This study provides basic information about the chemical and bioactive comparison of FPG, FPQ, and FPN, indicating that protopanaxtriol-type ginsenosides and malonyl-ginsenosides may play a key role in their enhancing immunity properties.
TL;DR: Evaluated polyamines that serve as early diagnostic and cancer progression markers as well as drug evaluation for lung cancer showed that increased N-acetylputrescine, cadaverine and 1,3-diaminopropane levels were associated with progression of SCCL.
Abstract: // Ran Liu 1 , Pei Li 1 , Cathy Wenchuan Bi 2 , Ran Ma 3 , Yidi Yin 1 , Kaishun Bi 1 and Qing Li 1 1 School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China 2 Division of Life Science and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Hong Kong, China 3 School of Basic Medical Sciences, Liaoning University of Traditional Chinese Medicine, Shenyang, China Correspondence to: Qing Li, email: lqyxm@hotmail.com Keywords: polyamine, SCCL, cancer and medication biomarkers, targeted metabolomics Received: April 28, 2017 Accepted: June 16, 2017 Published: July 17, 2017 ABSTRACT Polyamines have been widely investigated as potential biomarkers for various types of cancers, including lung cancer, which is one of the most common causes of death from cancer worldwide. This study was carried out to evaluate the value of polyamines that serve as early diagnostic and cancer progression markers as well as drug evaluation for lung cancer (squamous cell carcinoma of lung, SCCL). SCCL was induced in Wistar rats by intratracheal instillation of 3-methylcholanthrene and treated with three different anti-cancer drugs, Aidi injections, fluorouracil, and a combination of them. After carcinogenesis for 28, 70 and 98 days and therapy for 28 and 56 days, the polyamine levels in plasma of SCCL, healthy and treated rats were determined using a UHPLC-MS/MS assay base on the means of targeted metabolomics. Results showed that increased N-acetylputrescine, cadaverine and 1,3-diaminopropane levels were associated with progression of SCCL. The levels of cadaverine and 1,3-diaminopropane returned to normal after administration of the three different kinds of anticancer drug. In addition, the suitability of using N-acetylputrescine, cadaverine and 1,3-diaminopropane as biomarkers was confirmed by PLS-DA and ROC analysis. It can provide an innovative and effective way for the clinical diagnosis, prevention and treatment of lung cancer, and stimulate a theoretical basis for the design and development of new anticancer drugs. At the same time, this increased the clinical options for polyamines as cancer biomarkers.
TL;DR: Two novel alkaloids were isolated from Portulaca oleracea L., and spectroscopic methods including 1D and 2D nuclear magnetic resonance and high-resolution electrospray ionisation quadrupole-time of flight mass spectrometer spectrometry techniques are employed to determine their structures.
TL;DR: This study indicated licoflavone plays the role of treating gastric ulcer by regulating inflammation mediators and amino acid metabolism, and demonstrated that metabolomics technology combined with gene technology is a useful tool to search different metabolites and to dissect the potential mechanisms of traditional Chinese medicine (TCM) in treating gastrics ulcer.
TL;DR: The successful establishment of a hypothyroidism model is revealed and provides a new way to explore the efficiency of Chinese medicine on the basis of the relationship between drug property and effects on substance and energy metabolism.
TL;DR: Fibrous sheath interacting protein 1 is a signaling partner to HER2, and that FSIP inhibition reduces cell growth and invasiveness in HER2-positive breast cancer cells, and may become a potential target for breast cancer therapy.
Abstract: Fibrous sheath interacting protein 1 (FSIP1), a spermatogenesis-related testicular antigen, is expressed in abundance in breast cancers, particularly in those overexpressing human epidermal growth factor receptor 2 (HER2); however, little is known about its role in regulating the growth and metastasis of breast cancer cells. We and others have shown previously that FSIP1 expression in breast cancer correlates positively with HER2-positivity, recurrence, and metastases and negatively with survival. Here, using coimmunoprecipitation and microscale thermophoresis, we find that FSIP1 binds to the intracellular domain of HER2 directly. We further show that shRNA-induced FSIP1 knockdown in SKBR3 and MCF-7 breast cancer cells inhibits proliferation, stimulates apoptosis, attenuates epithelial–mesenchymal transition, and impairs migration and invasiveness. Consistent with reduced proliferation and enhanced apoptosis, xenotransplantation of SKBR3 cells stably transfected with sh-FSIP1 into nu/nu mice results in reduced tumor volumes compared with sh-NC transplants. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) mapping using sh-FSIP1 gene signature yielded associations with extracellular matrix protein pathways, and a reduction in SNAI2 protein expression was confirmed on Western blot analysis. Complementarily, interrogation of the Connectivity Map using the same gene signature yielded, as top hits, chemicals known to inhibit epithelial–mesenchymal transition, including rapamycin, 17-N-allylamino-17-demethoxygeldanamycin, and LY294002. These compounds phenocopy the effects of sh-FSIP1 on SKBR3 cell viability. Thus, FSIP1 suppression limits oncogenesis and invasiveness in breast cancer cells and, considering its absence in most other tissues, including normal breast, may become a potential target for breast cancer therapy.
TL;DR: The neuroprotective effects of ginseng protein (GP) and its possible mechanisms in a cellular and animal model of AD indicate that the anti‐AD mechanism of GP was likely to activate the CREB pathway through multiple channels.
Abstract: Ginseng (Panax ginseng C.A. Meyer) is one of the most widely used herbal medicines worldwide. The present study evaluated the neuroprotective effects of ginseng protein (GP) and its possible mechanisms in a cellular and animal model of AD. The results demonstrated that GP (10–100 µg/mL) significantly improved the survival rate of neurons and reduced the cells' apoptosis and the mRNA expression of caspase-3 and Bax/Bcl-2. In addition, GP (0.1 g/kg) significantly shortened the escape latency, prolonged the crossing times and the percentage of residence time; reduced the level of Aβ1–42 and p-tau, the activity of T-NOS and iNOS, and the content of MDA and NO, improved the activity of SOD, the concentration of cAMP and the protein expression of p-PKA/PKA and -CREB/CREB. The results demonstrated that GP significantly inhibited Alzheimer-like pathophysiological changes induced by Aβ25–35 or H2O2 in cells or those induced by D-gal/ Al in animals. These neuroprotective effects of GP may be associated with the cAMP/PKA/CREB pathway. Also, in combination with our previous studies, these results indicate that the anti-AD mechanism of GP was likely to activate the CREB pathway through multiple channels. Copyright © 2016 John Wiley & Sons, Ltd.
TL;DR: It is concluded that MENK could exert antitumor effect through precisely regulating opioid receptor mediated functions of DCs, and MENK treated DCs may serve as a new immunotherapy approach against tumor.