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Since the number of features of the dataset is much higher than the number of patterns, the higher the dimension of the data, the greater the impact on the learning algorithm. Dimension disaster has become an important problem. Feature selection can effectively reduce the dimension of the dataset and improve the performance of the algorithm. Thus, in this paper, A feature selection algorithm based on P systems (P-FS) is proposed to exploit the parallel ability of cell-like P systems and the advantage of evolutionary algorithms in search space to select features and remove redundant information in the data. The proposed P-FS algorithm is tested on five UCI datasets and an edible oil dataset from practical applications. At the same time, the P-FS algorithm and genetic algorithm feature selection (GAFS) are compared and tested on six datasets. The experimental results show that the P-FS algorithm has good performance in classification accuracy, stability, and convergence. Thus, the P-FS algorithm is feasible in feature selection. [ABSTRACT FROM AUTHOR]

Abstract Chronic myeloid leukemia (CML) responds well to BCR-ABL tyrosine kinase inhibitors (TKI), such as imatinib and dasatinib. However, these inhibitors have been less effective as single agents in the blast phase-CML. In this work, we show that anisomycin, a clinically available drug, targets CML cells at all stages of development and enhances BCR-ABL TKIs' efficacy. Anisomycin at nanomolar concentration inhibits proliferation and induces apoptosis in a panel of CML cell lines in a dose-dependent manner. It induces apoptosis CD34 stem/progenitor cells isolated from patients with blast phase CML. Using colony formation and serial replating assays, we further show that anisomycin inhibits CML CD34 cell differentiation, proliferation and self-renewal. Additionally, anisomycin is less effective in normal bone marrow (NBM) CD34 cells, suggesting the selective anti-leukemia activity of anisomycin. Combination of anisomycin with imatinib or dasatinib achieves significantly better efficacy than TKI alone in leukemia cell lines and patient samples while sparing normal counterparts. Mechanistically, we demonstrate that p38 MAPK/JNK activation is not required for anti-leukemia activities of anisomycin. Instead, anisomycin displays preferential inhibitory effects to Wnt/β-catenin-mediated signaling in CML. Our work provides the preclinical evidence on the potent efficacy of anisomycin in leukemia and its mechanisms of action. Our work suggests that anisomycin is a potential drug to overcome resistance to BCR-ABL TKI treatment in blast phase CML. Highlights • Anisomycin effectively targets CML cell lines and CD34 stem/progenitor cells. • Anisomycin has little or no effect on normal bone marrow (NBM) CD34 cells. • Anisomycin acts on CML cells through inhibiting Wnt/β-catenin signaling pathway. • Anisomycin augments the effects of BCR-ABL TKI in CML. [ABSTRACT FROM AUTHOR]

Epigallocatechin-3-gallate (EGCG) is a major catechin in green tea with functions of antioxidant, anti-proliferative, anti-inflammatory and attenuating metabolic syndrome. In this study, rat model of benign prostatic hyperplasia (BPH) accompanied with metabolic syndrome was induced by fed on high-fat diet for 12 weeks combined with testosterone injection (10 mg/kg/d) from 9th to 12th weeks. EGCG was orally given from 9th to 12th weeks. Finally, the levels of glucose, total cholesterol, triglyceride, prostate weight, insulin-like growth factors (IGFs), inflammatory cytokines, antioxidant enzymes, and prostatic expression of IGF binding protein-3 (IGFBP-3) and peroxisome proliferator activated receptors (PPARs) were evaluated. It was found that EGCG significantly decreased the levels of glucose, total cholesterol, triglyceride, IGFs, and inflammatory cytokines, normalized the activities of antioxidant enzymes, as well as increased the prostatic expression of IGFBP-3 and PPARs. These results indicated that EGCG was able to exert anti-BPH activities in metabolic syndrome rats. [ABSTRACT FROM AUTHOR]

The ubiquitin–proteasome system (UPS) plays an important role in virus–host interactions. However, the mechanism by which the UPS is involved in innate immunity remains unclear. In this study, we identified a novel major latex protein-like protein 43 (NbMLP43) that conferred resistance to Nicotiana benthamiana against potato virus Y (PVY) infection. PVY infection strongly induced NbMLP43 transcription but decreased NbMLP43 at the protein level. We verified that B-box zinc finger protein 24 (NbBBX24) interacted directly with NbMLP43 and that NbBBX24, a light responsive factor, acted as an essential intermediate component targeting NbMLP43 for its ubiquitination and degradation via the UPS. PVY, tobacco mosaic virus, (TMV) and cucumber mosaic virus (CMV) infections could promote NbMLP43 ubiquitination and proteasomal degradation to enhance viral infection. Ubiquitination occurred at lysine 38 (K38) within NbMLP43, and non-ubiquitinated NbMLP43(K38R) conferred stronger resistance to RNA viruses. Overall, our results indicate that the novel NbMLP43 protein is a target of the UPS in the competition between defense and viral anti-defense and enriches existing theoretical studies on the use of UPS by viruses to promote infection. [ABSTRACT FROM AUTHOR]

Context: Cyclosorus acuminatus (Houtt.) Nakai (Thelypteridaceae) is used in Chinese traditional medicine for inflammation and pyretic stranguria. Objective: This study investigates the prostatic protective potential of the flavonoid-rich [(2 S)-5,7,5′-trihydroxyflavanone glycosides] fraction from C. acuminatus (FCA). Materials and methods: Chronic non-bacterial prostatitis (CNBP) was induced by injecting 20 μl of 1% carrageenan into the rat prostate. Subsequently, FCA (150 or 300 mg/kg/d) was orally given once a day for 4 weeks. Finally, the levels of proinflammatory cytokines and the prostatic expression of peroxisome proliferator activated receptor-γ (PPAR-γ) were evaluated. Results: Treatment with 300 mg/kg/d FCA ameliorated the carrageenan-induced higher prostatic index (PI) state and proinflammatory cytokines levels (NFκB from 2602 ± 588 to 1348 ± 300 pg/ml, TNF-α from 151.6 ± 10.4 to 126.0 ± 3.52 pg/ml, IL-1β from 153.7 ± 14.8 to 63.9 ± 6.7 pg/ml, COX-2 from 313.3 ± 16.5 to 263.1 ± 15.1 pg/ml, PGE from 1532 ± 130 to 864 ± 126 pg/ml, NOS from 33.7 ± 3.0 to 23.6 ± 1.6 U/mg protein, and NO from 40.3 ± 2.9 to 27.1 ± 2.9 μmol/g protein) as well as regulated the prostatic expression of PPAR-γ (increased about 3.50-fold) when compared to the rat model of prostatitis. Discussion and conclusion: FCA could exert a prostatic protective response via modulating the prostatic expression of PPAR-γ and eventually alleviating the NFκB dependent inflammatory response. [ABSTRACT FROM AUTHOR]

Context: Pulmonary hypertension (PH) is a complication of numerous pulmonary conditions. Previous studies have confirmed that Selaginella doederleini has pharmacological effects against many cancers, and triflavones have been newly isolated as one of its active ingredients, with antioxidant and antitumor activities. The chronic hypoxia model is one of the models most used to study PH pathogenesis and treatment.Objective: The present study was designed to investigate the protective effects of triflavones from selaginella doederlleini against PH and on the proliferation and apoptosis of ASMCs in a hypoxia-induced PH model in rats.Methods: The research team performed an animal study.Setting: The study took place at the Tongji Medical College at the Huazhong University of Science and Technology in Wuhan, Hubei, PR China.Animals: The animals were 40 specific pathogen free (SPF), male SD rats weighing 200 ± 20 g each.Intervention: The animals were divided into 4 groups, with 10 animals in each group: (1) the control group, (3) the hypoxia group (PH group), (3) the control + triflavones group (Tri group) and (4) the hypoxia + triflavones group (PH + Tri group). The rats in 2 hypoxia groups were exposed to 10% oxygen to induce PH, and the animals in the 2 control groups were exposed to room air, both for 3 consecutive weeks. Animals in the 2 triflavones groups were injected with 200 μL of triflavones-100 mg/mL dissolved in 0.9% normal saline-and the animals in the control and PH groups were injected with 200 μL of 0.9% normal saline.Outcome Measures: In vitro, the primary aorta smooth muscle cells (ASMCs) were isolated, and the proliferation and apoptosis of the ASMCs were assayed by CCK-8 kit and flow cytometry. The expression levels of the alpha-smooth muscle actin (α-SMA), transforming growth factor beta 1 (TGF-β1), and phosphoinositide 3-kinases (P13K)/ protein kinase B (Akt) in the ASMCs were also assayed by Western blot.Results: Triflavones effectively decreased mPAP, the ratio of RV/ (LV + S), and the thickness of the arteries of the PH + Tri group. Furthermore, triflavones reversed the increased proliferation and inhibited apoptosis induced by chronic hypoxia for that group. Hypoxia increased TGF-β1 protein expression and the activation of P13K/Akt, as shown in the PH group, and was abrogated by the triflavones.Conclusion: Triflavones are promising protective agents against PH due to their inhibitory effects on vascular remodeling through P13K/Akt signaling. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated that a family history of breast cancer is considered a risk factor, and hereditary factors may be involved in breast cancer pathogenesis. Next-generation sequencing techniques were used to analyze 111 cancer-associated genes in patients with breast cancer with a familial history of malignant tumors in the pre-experiment and a novel variant, receptor tyrosine-protein kinase erbB-2 (ERBB2) c.338G>A: p.R113Q was identified in two cases of breast cancer. ERBB2 is considered an important oncogene, and overexpression or mutation of the ERBB2 gene may lead to the occurrence or metastasis of tumors. To assess a potential association between rs185670819 and breast cancer, 117 patients with breast cancer and a familial history of any cancer, who were diagnosed by experienced pathologists at the Xijing Hospital (Shaanxi, China) between July 2015 and December 2016, were recruited. The presence of the missense variant was confirmed using bi-directional Sanger sequencing of samples from the patients with breast cancer and 250 healthy controls. The effects of the missense mutation on the structure and function of ERBB2 were analyzed in silico. The missense variant, R113Q, in patients with breast cancer with a familial history of malignant tumors in China, was present in 8 patients [6.8% (95% CI: 3.21–13.45)] and 3 of 250 healthy controls [1.2% (95% CI: 0.31–3.76; OR=6.04, 95% CI: 1.573–23.214, P=0.009)]. Of the 8 patients with the R113Q variant, 6 patients had a family history of cancer of the digestive system. The present study suggests that ERBB2 c.338G>A: p.R113Q may be a potential risk factor in the development and progression of breast cancer. [ABSTRACT FROM AUTHOR]

Background/Aims: Cadmium (Cd) is an environmental pollutant with reproductive toxicity. Swertia mileensis is used in Chinese medicine for the treatment of prostatic deficits and named as Qing Ye Dan (QYD). This study was undertaken to investigate the potential protective effects of QYD against Cd-induced prostatic deficits. Method: Rat model of prostatic deficits was induced by 0.2 mg/kg/d CdCl2 subcutaneous injection for 15 days. The prostatic oxidative stress was evaluated by detecting the levels of malondialdehyde, nitric oxide, reduced/oxidized glutathione, total sulfhydryl groups and enzymatic antioxidant status. The prostatic inflammation was estimated by testing the levels of pro-inflammatory cytokines. The levels of epithelial-mesenchymal transition (EMT) markers E-cadherin, fibronectin, vimentin and a-smooth muscle actin were measured by qPCR analysis. Additionally, the prostatic expressions of transforming growth factor-ß1 (TGF-ß1), type I TGF-ß receptor (TGF-ßRI), Smad2, phosphorylation-Smad2 (p-Smad2), Smad3, p-Smad3, Smad7, nuclear related factor-2 (Nrf- 2), heme oxygenase-1 (HO-1), B-cell CLL/lymphoma (Bcl)-2 and Bcl-2-associated X protein (Bax) were measured by western blot assay. Results: It was found that QYD ameliorated the Cd-induced prostatic oxidative stress and inflammation, attenuated prostatic EMT, inhibited the TGF-ß1/Smad pathway, increased Bcl-2/Bax ratio and enhanced the activity of Nrf-2/HO-1 pathway. Conclusion: These results showed that QYD could ameliorate Cd-induced prostatic deficits via modulating Nrf-2/HO-1 and TGF-ß1/Smad pathways. [ABSTRACT FROM AUTHOR]

Plateau frostbite (PF) treatments have remained a clinical challenge because this condition injures tissues in deep layers and affected tissues exhibit unique pathological characteristics. For instance, low-frequency pulsed electromagnetic field (PEMF) can affect tissue restoration and penetrate tissues. Therefore, the effect of PEMF on PF healing should be investigated. This study aimed to evaluate the effects of low-frequency PEMF on PF healing systematically. Ninety-six Sprague-Dawley rats were randomly and equally divided into three groups: normal control, partial thickness plateau frostbite (PTPF), and PTPF with low-frequency PEMF exposure (PTPF + PEMF). PTPF wounds were induced in the dorsum of the rats. The PTPF + PEMF group was exposed to low-frequency PEMF daily. During PF healing, wound microcirculation in each group was monitored through contrast ultrasonography. Wound appearance, histological observation, and wound tensile strength were also evaluated. Results showed that the rate of the microcirculation restoration of the PTPF + PEMF group was nearly 25% faster than that of the PTPF group, and wound appearance suggested that the healing of the PTPF group was slower than that of the PTPF + PEMF group. Histological observation revealed that PEMF accelerated the growth of different deep tissues, as confirmed by tensile strength examination. Low-frequency PEMF could penetrate PF tissues, promote their restoration, and provide a beneficial effect on PF healing. Therefore, this technique may be a potential alternative to treat PF. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) pollution is a serious environmental problem. Kidney is a main target organ of Cd toxicity. This study was undertaken to investigate the potential protective effects of epigallocatechin-3-gallate (EGCG) against chronic renal injury and fibrosis induced by CdCl 2 . Rat model was induced by exposing to 250 mg/L CdCl 2 through drinking water. The renal function was evaluated by detecting the levels of blood urea nitrogen (BUN) and serum creatinine (SCR). The oxidative stress was measured by detecting the levels of malondialdehyde (MDA), nitric oxide (NO), reduced glutathione/oxidized glutathione (GSH/GSSG) and renal enzymatic antioxidant status. Additionally, the renal levels of transforming growth factor-β1 (TGF-β1), Smad3, phosphorylation-Smad3 ( p p-Smad3), α-smooth muscle actin (α-SMA), vimentin and E-cadherin were measured by western blot assay. Renal levels of microRNA-21 (miR-21), miR-29a/b/c and miR-192 were measured by quantitative RT-PCR. It was found that EGCG ameliorated the CdCl 2 -induced renal injury, inhibited the level of oxidative stress, normalized renal enzymatic antioxidant status and E-cadherin level, as well as attenuated the over generation of TGF-β1, p p-Smad3, vimentin and α-SMA. EGCG also decreased the production of miR-21 and miR-192, and enhanced the levels of miR-29a/b/c. These results showed that EGCG could attenuate Cd induced chronic renal injury. [ABSTRACT FROM AUTHOR]

Chronic myeloid leukemia (CML) responds well to BCR-ABL tyrosine kinase inhibitors (TKI), but becomes resistant to TKIs after it progresses to blast phase (BP). Here we show that niclosamide, a FDA-approved anthelmintic drug, enhances the sensitivity of BP-CML cells to dasatinib (2nd generation of BCR-ABL TKI) through inhibiting Erk/Mnk1/eIF4E signaling pathway. Niclosamide dose-dependently inhibits proliferation and induces apoptosis in a panel of CML cell lines. It also selectively targets BP-CML CD34 stem/progenitor cells through inducing apoptosis, inhibiting colony formation and self-renewal capacity while sparing normal bone marrow (NBM) counterparts. In addition, combination of niclosamide and dasatinib is synergistic in CML cell lines and BP-CML CD34 cells. Importantly, niclosamide inhibits phosphorylation of Erk, Mnk1 and eIF4E in CML cells. Overexpression of phosphomimetic but not nonphosphorylatable form of eIF4E reverses the inhibitory effects of niclosamide, suggesting that eIF4E inhibition is required for the action of niclosamide in CML. Compared to NBM, the increased levels of eIF4E and its activity in CML CD34 cells might explain the selective toxicity of niclosamide in CML versus NBM. We further show that dasatinib time-dependently induces eIF4E phosphorylation. The combination of eIF4E depletion and dasatinib results in similar effects as the combination of niclosamide and dasatinib, suggesting that niclosamide enhances dasatinib through targeting eIF4E. Our work is the first to demonstrate that niclosamide is a potential drug to overcome resistance to BCR-ABL TKI treatment in BP-CML. Our findings also suggest the therapeutic value of Erk/Mnk/eIF4E in CML treatment. [ABSTRACT FROM AUTHOR]

Ethnopharmacology relevance Calculus Bovis , also known as Niuhuang, is a rare traditional Chinese medicine that has been widely used in China for 2000 years in pharmacology for sedation, anti-spasm, relieving fever, diminishing inflammation and recovering gallbladder functions. Aim of the study This study aimed to investigate the choleretic potential and molecular responses in rats to Calculus Bovis (CB) administration after 17α-ethynylestradiol (EE)-induced cholestasis. Material and methods CB (50 and 100 mg/kg per day) was intragastrically (i. g.) given to experimental rats for five consecutive days in coadministration with EE (5 mg/kg daily for five days, s.c.). The levels of serum biomarkers were determined biochemically. The histopathology of the liver tissue was evaluated. Expression of bile salt export pump (BSEP) and multidrug resistance-associated protein 2 (MRP2) were studied by western blot and immunohistochemical assay. The expression of Akt and phospho-Akt (pAkt) were also measured by western blot. Results In response to EE, CB treatment significantly prevented an increase in serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyltransferase (GGT) and total bilirubin (TBIL). CB treatment also repaired tissue lesions caused by EE. Western blots showed that EE significantly decreased the protein expression of BSEP and MRP2. EE also dramatically increased levels of pAkt and decreased levels of Akt. Compared to the EE group, CB treatment increased levels of hepatic BSEP and MRP2 while pAkt levels decreased and Akt levels increased. Immunohistochemistry also indicated that EE decreased the expression of BSEP and MRP2. LY294002 is a selective PI3K inhibitor and showed similar beneficial effects as CB. Decreased expression of BSEP and MRP2 caused by EE were also prevented by LY294002 treatment. Conclusion Calculus Bovis administration can alleviate liver injury and up-regulate the expression of BSEP and MRP2 in 17α-ethynylestradiol-induced cholestasis by a mechanism that may involve inhibiting the activated PI3K/Akt signaling pathway. [ABSTRACT FROM AUTHOR]

Green tea ( Camellia sinensis ) is an extremely popular beverage worldwide. Epigallocatechin-3-gallate (EGCG) is one of the major catechins isolated from green tea and contributes to its beneficial therapeutic functions including antioxidant, anti-inflammatory and anti-cancer effects. However, the effect of EGCG on mastitis is not yet known. This study was to investigate the protective potential of EGCG against mastitis in rats. The rat mastitis model was induced by injecting lipopolysaccharide (LPS) into the duct of mammary gland. The mammary gland was collected after the experimental period. The levels of mammary oxidative stress and inflammatory responses were assessed by measuring the local activities of antioxidant enzymes and the levels of inflammatory cytokines. The mammary expressions of mitogen-activated protein kinases (MAPKs), nuclear factor κB-p65 (NFκB-p65) and hypoxia-inducible factor-1α (HIF-1α) were evaluated by western blot analysis. It was found that EGCG obviously normalized LPS-induced low activities of antioxidant enzymes as well as decreased the high levels of inflammatory cytokines. Additionally, EGCG inhibited the mammary over-expression of MAPKs, NFκB-p65 and HIF-1α. These results indicated that EGCG was able to attenuate LPS-induced mastitis in rats by suppressing MAPK related oxidative stress and inflammatory responses. [ABSTRACT FROM AUTHOR]

Rosa rugosa (Thunb.) is used in Chinese traditional medicine with the functions of promoting blood circulation, relieving the depressed liver and attenuating breast disorders. This study was to investigate the anti-hyperplasia effects of the polyphenols-rich fraction from R. rugosa (FRR) in rat. Rat model of hyperplasia of mammary gland (HMG) was induced by intramuscularly injected with estrogen (0.5 mg/kg/d) for 25 days, and followed with progestogen (5 mg/kg/d) for another 5 days. Meanwhile, FRR was orally given for 30 days. Then, the levels of estradiol and oxidative stress were assessed. The mammary expressions of AKT and JNK were evaluated by Western blot analysis. The expressions of NFκB-p65, COX-2 and VEGF were measured by immunohistochemical analysis. The whole results indicated that FRR could exert anti-hyperplasia effects in rat via modulating the mammary expression of JNK and AKT, as well as alleviating the NFκB related oxidative stress and inflammatory responses. [ABSTRACT FROM AUTHOR]

Abstract: GX1 is a tumor targeting peptide. In this study, we evaluated the antitumor efficacy of a GX1-derived fusion toxin, GX1-rmhTNFα, and investigated its targeting efficiency and pharmacokinetics in vivo using multimodality imaging. Flow cytometry revealed a greater level of cell apoptosis induced by GX1-rmhTNFα (27.1%) compared with rmhTNFα or a saline control (13.7% and 4.7%, respectively). SPECT (single-photon emission computed tomography) demonstrated high accumulation of GX1-rmhTNFα in tumor site. Biodistribution studies indicated GX1-rmhTNFα was cleared by the liver and kidney, and the drug may not cross the blood–brain barrier. In addition, bioluminescence imaging (BLI) showed that GX1-rmhTNFα caused a satisfactory delay in tumor growth in both subcutaneous and orthotopic cancer models. Contrast-enhanced ultrasound (CEUS) and CD31 staining revealed a loss in blood perfusion and vasculature. TUNEL and Ki67 staining validated the in vivo results. Biochemical analyses revealed limited renal and hepatic toxicity of GX1-rmhTNFα. This study demonstrated that GX1-rmhTNFα is a safe and potent anticancer agent that may have great potential for the targeted therapy of gastric cancer. [Copyright &y& Elsevier]

Subsequent to the publication of this article, the authors have realized that the name of the last-listed corresponding author, Liwen Liu, was spelt incorrectly as "Liwen Lu" in the correspondence details, even though the name was printed correctly as Liwen Liu in the author affiliations. Correspondence to: Dr Hongping Song or Dr Liwen Liu, Department of Ultrasonic Medicine, Xijing Hospital, The Fourth Military Medical University, 172 Chang Le Road, Xi'an, Shaanxi 710032, P.R. China. [Extracted from the article]