ABSTRACT
Based on bone metastasis potential of mouse breast cancer 4T1 cells, the bone disseminated breast tumor cells 4T1 (B-4T1) were acquired through the screening of 6-mercaptopurine. The characteristics of B-4T1 were studied by morphological observation, proliferation assay, expression of epithelial and mesenchymal cell markers detection, transcriptome sequencing, and tumor formation experiments. The results showed that B-4T1 was round and spindle-shaped than primary 4T1 cells, and its proliferation rate was reduced, as well as epithelial cell adhesion molecule (EpCAM) and E-cadherin expression. The transcript level of N-cadherin was increased in the B-4T1, but not vimentin, indicating that B-4T1 had partial epithelial mesenchymal transition. Besides, B-4T1 had higher fatty acid metabolism and better tumor formation capacity. This study lays the experimental foundation for the basic study of metastasis in breast cancer. All animal experiments in this paper were conducted in accordance with the standards of the Animal Ethics Committee of China Pharmaceutical University.
ABSTRACT
Idiopathic pulmonary fibrosis （IPF）， as a progressive lung disease， has a poor prognosis and no reliable and effective therapies. IPF is mainly treated by organ transplantation and administration of chemical drugs， which are ineffective and induce side effects， failing to meet the clinical needs. Therefore， developing safer and more effective drugs has become an urgent task， which necessitates clear understanding of the pathogenesis of IPF. The available studies about the pathogenesis of IPF mainly focus on macrophage polarization， epithelial-mesenchymal transition （EMT）， oxidative stress， and autophagy， while few studies systematically explain the principles and links of the pathogeneses. According to the traditional Chinese medicine theory， Qi deficiency and blood stasis and Qi-Yang deficiency are the key pathogeneses of IPF. Therefore， the Chinese medicines or compound prescriptions with the effects of replenishing Qi and activating blood， warming Yang and tonifying Qi， and eliminating stasis and resolving phlegm are often used to treat IPF. Modern pharmacological studies have shown that such medicines play a positive role in inhibiting macrophage polarization， restoring redox balance， inhibiting EMT， and regulating cell autophagy. However， few studies report how Chinese medicines regulate the pathways in the treatment of IPF. By reviewing the latest articles in this field， we elaborate on the pathogenesis of IPF and provide a comprehensive overview of the mechanism of the active ingredients or compound prescriptions of Chinese medicines in regulating IPF. Combining the pathogenesis of IPF with the modulating effects of Chinese medicines， we focus on exploring systemic treatment options for IPF， with a view to providing new ideas for the in-depth study of IPF and the research and development of related drugs.
ABSTRACT
Objective To analyze therapeutic effect of savolitinib in patients with stage Ⅲ/Ⅳ non-small cell lung cancer (NSCLC). Methods A total of 95 patients with MET 14 exon (METex14) jumping mutation in stage Ⅲ/Ⅳ NSCLC were divided into a control group (47 cases) and an observation group (48 cases) through a random-number table method. The patients in the control group were treated with crizotinib, whereas those in the observation group were treated with savolitinib. The clinical efficacy and incidence of toxic side effects in both groups were evaluated through a chi-square test, and survival was evaluated through Kaplan-Meier survival analysis. Results Compared with control group (31.91% and 70.21%), the objective response rate and disease control rate of the observation group were 52.08% and 87.50%, respectively (P<0.05). According to Kaplan-Meier survival analysis, the overall survival and progression free survival rates in the observation group were higher than those in the control group (Log rank χ2=8.003, 4.528; P=0.005, 0.033). No statistically significant difference in the degree of toxic side effects was found between the groups (P>0.05). Conclusion Savolitinib can improve the efficacy of treatment for stage Ⅲ/Ⅳ METex14 skip mutation NSCLC patients, prolong survival, enhance the tolerance of patients to savolitinib, and facilitate the management of adverse reactions.
ABSTRACT
Aim To investigate the effect of Xuefu Zhuyu decoction on transforming growth factor-β1(TGF-β1 ) -induced endothelial-to-mesenchymal transition (EndMT) of pulmonary microvascular endothelial cells ( PMVEC), and further analyze the mechanism related to the TGF-β1/Smad signaling pathway. Method To construct an EndMT cell model, PMVEC was treated with TGF-β1 (5 μg · L
ABSTRACT
Aim To investigate the targeting mechanism of miR-23b on PINKl/Parkin pathway in transdifferentiation of NRK-52E cellsinduced by TGF-β1, and to elucidate the intervention mechanism of Qingshen granules drug-containing serum on NRK-52E cell transdifferentiation. Methods Ultra-high performance liquid chromatography ( UPLC ) fingerprinting method was used to analyze Qingshen granules. The NRK-52E transdifferentiation model induced by TGF-β1 was constructed. The NRK-52E cells were divided into simulated no-load control group, miR-23b-5p simulated group, inhibitor no-load control group, and miR-23b-5p inhibitor group, after transfection with siRNA, and the effect of miR-23b-5p on PINK1 expression was ob-served. The NRK-52E cells were then divided into normal group, TGF-(31 group, Qingshen granule group, miR-23 b-mimic group, miR-23 b-mimic group, and miR-23b-mimic + Qingshen granule group. Western blot was used to detect the expression of Pinkl, Parkin, LC3 n, Beclin-1, P62 and a-SMA proteins, and RT- PCR was used to detect the expression of miR-23 b-5p, Pinkl, Parkin, Beclin-1 and a-SMA mRNA in NRK- 52E cells. Dual-Luciferase Reporter gene experiment was used to detect the targeting relationship between miR-23b-5p and PINKL Results UPLC fingerprinting method found 11 active components in Qingshen granules. After overexpression of miR-23b-5p, the expression of PINkl mRNA significantly increased (P 0. 05 ). The experimental results showed that the expressions of miR- 23b-5p, Pinkl, Parkin, Beclin-1, LC3 II and LC3 II/ I ratio in TGF-β1 group were significantly lower than those in normal group, but the expressions of P62 and a-SMA were significantly higher than those in normal group ( P <0.05). The expressions of miR-23 b-5 p, Pinkl, Parkin, Beclin-1, LC3 II and LC3 11/ I ratio in Qingshen granule group and miR-23 b-mimic group were significantly higher than those in TGF-β1 group, and the expressions of P62 and a-SMA were significantly lower than those in TGF-β1 group (P < 0. 05 ). The performance of miR-23 b-mimic + Qingshen granule group was better than that of miR-23 b-mimic group (P < 0. 05 ). Conclusions Qingshen granules can up- regulate the expression of miR-23b-5p in NRK-52E cellsand inhibit the transdifferentiation process of NRK- 52E cells by enhancing the mitochondrial autophagy activity mediated by PINKl/Parkin pathway.
ABSTRACT
Aim To investigate the effect of colchicine on lipopolysaccharide (LPS) induced endothelial to mesenchymal transition (EndMT) in human umbilical vein vascular endothelial cells (HUVECs) and its related mechanisms. Methods The EndMT model was established by treating HUVECs with LPS. Cell proliferation rate was detected by CCK-8 assay, cytotoxicity was detected by LDH assay, and the optimal drug concentration was screened. The cells were divided into the normal control group, the normal control + colchicine (10 nmol • L) group, the LPS (10 mg • L) model group, and the LPS + colchicine (10 nmol • L) group. The morphologic changes of the cells were observed under an inverted microscope, the cell migration ability was detected by Transwell assay, and the ability of tube formation was analyzed by tube formation assay. The expression of endothelial markers (CD31/ VE-cadherin) and mesenchymal cell markers (a-SMA/FSP-1) were detected by Western blot. NF-KB inhibitor was used to detect the changes in related signaling pathways. Results CCK-8 and LDH experiments showed that 10 nmol • L colchicine was the optimal concentration. LPS could induce morphological changes in HUVECs, and colchicine could reverse morphological changes in HUVECs to a certain extent. Transwell experiment showed that the migration ability of HUVECs in the LPS treatment group was significantly enhanced (P < 0. 05), and colchicine could significantly reverse this phenomenon (P < 0. 05) . Tube formation experiment showed that LPS decreased the endothelial tube formation ability of HUVECs (P < 0. 05), while colchicine treatment markedly improved LPS-induced tube formation defects (P < 0. 05) . Western blot assay showed that after colchicine co-cultured with LPS, the expression levels of CD31 and VE-cadherin significantly increased compared with the model group (P < 0. 05), while the expression levels of a-SMA and FSP-1 significantly decreased compared with the model group (P < 0. 05) . During the induction of EndMT by LPS, colchicine could inhibit the activation of the NF-KB/Snail signaling pathway. Conclusions Colchicine can effectively inhibit EndMT induced by LPS, and the mechanism may be related to the regulation of the NF-KB/Snail signaling pathway.
ABSTRACT
OBJECTIVE To investigate the effects of polydatin （PD） on cell proliferation， migration， invasion and tumor growth of acute myeloid leukemia （AML）. METHODS Human AML cell KG-1 were divided into normal group， PD low-， medium- and high-concentration groups （10， 30， 60 μmol/L PD）， SQ22536 group [cyclic adenosine monophosphate （cAMP） inhibitor， 100 μmol/L]， high concentration of PD+SQ22536 group （60 μmol/L PD+100 μmol/L SQ22536）. The effects of PD on cell activity， apoptotic rate， invasion and migration ability， cAMP level， the expression of epithelial-mesenchymal transition （EMT） related proteins and protein kinase A （PKA） were investigated. Using BALB/c nude mice as subjects， a transplanted tumor model of AML nude mice was induced by subcutaneous inoculation of KG-1 cell suspension and then divided into control group， PD group， SQ22536 group and PD+SQ22536 group （with 6 mice in each group）. The effects of PD on tumor volume and mass were measured. RESULTS Compared with the normal group or control group， the cell viabilities， the number of migrating cells， the number of invasive cells， the relative expressions of vimentin and Snail as well as the tumor volume and mass were decreased significantly in PD groups， while the apoptotic rates， cAMP levels， the relative expressions of E-cadherin and PKA were significantly increased， with a dose-dependent manner （P＜0.05）. SQ22536 had opposite effects on cells and nude mice compared to PD， and could significantly reverse the anti-tumor activity of PD （P＜0.05）. CONCLUSIONS PD may inhibit the proliferation， migration， invasion and EMT process of KG-1 cells， induce apoptosis， and inhibit tumor growth， by activating the cAMP/PKA signaling pathway， thereby exerting anti-AML effects.
ABSTRACT
Objective To investigate the therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) for radiation-induced lung injury (RILI) and the underlying mechanism. Methods Forty-five healthy adult male C57BL/6 mice were randomly divided into control, model, and BMSCs groups. The model and BMSCs groups received a single irradiation dose of 20 Gy to the chest, while the control group did not receive X-ray irradiation. For the BMSCs group, an injection of 1 × 106 BMSCs cells was administered via the tail vein within 6 h after irradiation. In the 5th week, the lung tissue was taken to observe pathological changes with HE staining; examine the expression of the inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) with immunohistochemical staining; observe the polarization of macrophages with immunofluorescence staining; and measure the expression of the epithelial-mesenchymal transition markers E-cadherin, N-cadherin, and vimentin proteins by Western blot. Results After radiation, the model group developed pulmonary vasodilation and congestion with septal thickening and inflammatory cell infiltration, and these changes were markedly reduced in the BMSCs group. The model group showed significantly down-regulated expression of IL-6 and TNF-α compared with significantly increased levels in the model group (P < 0.01, P < 0.05). Treatment with BMSCs significantly increased the polarization of lung macrophages towards the M2 type, while significantly decreasing the abnormally increased N-cadherin and vimentin levels in RILI mice (P < 0.05, P < 0.01). Conclusion BMSCs have therapeutic effects for RILI mice, which may be through promoting macrophage polarization from M1 to M2.
ABSTRACT
Objective To investigate the effects of TFF3 overexpression on the proliferation, migration, and invasion ability of colorectal cancer HT29 cells and the mechanisms involved in cancer metastasis. Methods HT29 cells were transfected with pIRES2-TFF3, and the expression levels of mRNAs and proteins related to TFF3 gene, TWIST1/TRIB3 signaling pathway, and epithelial-mesenchymal transition (EMT) were detected by qRT-PCR and Western blot. The proliferation, migration, and invasion ability of HT29 cells were detected by the CCK-8, cell scratch, and Transwell assays. Changes in cell morphology after TFF3 overexpression were observed through transmission electron microscopy. Results After the HT29 cells were transfected with pIRES2-TFF3, the expression levels of TFF3 mRNA and protein significantly increased (P<0.01); cell proliferation, migration, and invasion were significantly enhanced (P<0.01); and the expression of related genes, such as TWIST1, TRIB3, Vimentin, and Snail were significantly upregulated. By contrast, the expression of E-cadherin significantly decreased (P<0.05). Various changes in cell morphology were observed after TFF3 overexpression, such as decrease in cell junctions, loss of cilia, formation of pseudopodia, and increase in fusiform cells. Conclusion TFF3 overexpression may promote EMT in colorectal cancer cells through the Twist1/TRIB3 signaling pathway, increase their metastatic potential, and accelerate the malignant progression of colorectal cancer.
ABSTRACT
ObjectiveTo investigate the role of the Wnt1/β-catenin signaling pathway in the intervention of medicated serum of Buyang Huanwutang （BYHWT） in endothelial-to-mesenchymal transition （EndMT） of human pulmonary artery endothelial cells （HPAECs） as well as its related mechanisms. MethodMedicated serum of BYHWT was prepared by gavage to New Zealand rabbits with a dosage of 53.36 g·kg-1·d-1 after decocting the medicine as usual. In addition， the same volume of normal saline was used to prepare blank serum. The HPAECs were cultured in vitro， and then induced by the transforming growth factor-β1 （TGF-β1） to establish the EndMT model. Five groups were established： blank group （10% blank serum）， model group （TGF-β1+10% blank serum）， low-dose BYHWT group （TGF-β1+2.5% medicated serum+7.5% blank serum）， medium-dose BYHWT group （TGF-β1+5% medicated serum+5% blank serum） and high-dose BYHWT group （TGF-β1+10% medicated serum）. Through Western blot， the expressions of Wnt1， β-catenin， and glycogen synthase kinase-3β （GSK-3β） were detected. In order to further clarify the mechanism of the Wnt1/β-catenin signaling pathway in the intervention of the medicated serum of BYHWT in inhibiting EndMT， the overexpression of β-catenin was confirmed by polymerase chain reaction after plasmid of overexpression β-catenin was constructed and transfected into the HPAECs. The HPAECs were intervened by 10% medicated serum with the optimal effect in previous studies. Then， they were divided into another five groups： the blank group （10% blank serum）， the model group （TGF-β1+10% blank serum）， the BYHWT group （TGF-β1+10% medicated serum）， the BYHWT+overexpression plasmid control group （TGF-β1+10% medicated serum+blank plasmid） and the BYHWT+β-catenin overexpression plasmid group （TGF-β1+10% medicated serum+β-catenin）. Apart from that， cell proliferation ability was detected by the methyl thiazolyl tetrazolium （MTT） method and cell migration ability by scratch assay and Transwell assay together. Immunofluorescence was adopted to detect the expressions of platelet endothelial cell adhesion molecule （PECAM-1/CD31）， vascular endothelial cadherin （VE-cadherin）， fibroblast-specific protein 1 （FSP1）， and α-smooth muscle actin （α-SMA）. ResultIn comparison to the blank group， the expressions of Wnt1 and β-catenin were significantly increased （P<0.01） while the expression of GSK-3β significantly decreased （P<0.01） in the model group. In comparison to the model group， the expressions of Wnt1 and β-catenin were significantly decreased （P<0.01） while the expression of GSK-3β was significantly increased （P<0.01） in the high-dose BYHWT group. The expression of β-catenin was significantly decreased （P<0.01） while the expression of GSK-3β was significantly increased （P<0.01） in the medium-dose BYHWT group. There was no significant difference in these indexes of the low-dose BYHWT group. In comparison to the blank group， proliferation and migration abilities were remarkably increased （P<0.01） and the immunofluorescence intensities of CD31 and VE-cadherin were decreased， while those of FSP1 and α-SMA were increased in the model group. In comparison to the model group， proliferation and migration abilities were significantly decreased （P<0.01） and the immunofluorescence intensities of CD31 and VE-cadherin were increased， while those of FSP1 and α-SMA diminished in the BYHWT group. Beyond that， the change trend of those indexes in the BYHWT+β-catenin overexpression plasmid group was consistent with that in the model group. In comparison to the BYHWT+overexpression plasmid control group， proliferation and migration abilities were significantly increased （P<0.01） and the immunofluorescence intensities of CD31 and VE-cadherin were decreased， while those of FSP1 and α-SMA were increased in the BYHWT+β-catenin overexpression plasmid group. ConclusionMedicated serum of BYHWT can inhibit EndMT of HPAECs by the Wnt1/β-catenin signaling pathway.
ABSTRACT
Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.
ABSTRACT
OBJECTIVE@#To assess acute toxicity, the in vitro and in vivo effects of methanol and ethyl acetate extracts (JME and JEE) of Jatonik polyherbal mixture on some mitochondria-related parameters and their effect on the activity of some liver enzymes.@*METHODS@#Acute toxicity of JME and JEE was determined using Lorke's method. In vitro and in vivo opening of the mitochondrial membrane permeability transition pore (MMPT pore) was spectrophotometrically assayed. Production of malondialdehyde (MDA) as an index of lipid peroxidation and the activity of mitochondrial ATPase was evaluated in vitro and in vivo and the effect of JME and JEE on the activity of liver enzymes such as alkaline phosphatase (ALP), aspartate and alanine aminotransferase (AST and ALT) and gamma-glutamyl transferase (GGT) was also investigated.@*RESULTS@#JME had an LD50 of 3 808 mg/kg b.w whereas JEE had an LD50 greater than 5 000 mg/kg b.w. of rats. After the rats have been fed with both extracts, a photomicrograph of a piece of liver tissue showed no apparent symptoms of toxicity. From the in vitro and in vivo studies, both extracts prompted intact mitochondria to open their MMPT pores. When compared to the control, lipid peroxide product release and ATPase activity were significantly increased (P < 0.05) in vitro and in vivo. The activities of AST, ALT, and GGT were all reduced at 50 mg/kg when treated with JME, but the activity of AST was considerably enhanced when treated with JEE (P < 0.05). The results revealed that both JME and JEE of the Jatonik polyherbal mixture had low toxicity, profound MMPTpore induction, and enhanced ATPase activity, but an increased MDA production.@*CONCLUSION@#Jatonik extracts may be a promising target for drug development in diseases where there is dysregulation of apoptosis, however, further studies are needed to better clarify the molecular mechanism involved in these phenomena.
ABSTRACT
ObjectiveTo investigate the effect of Dendrobium officinale polysaccharide （DOP）on CCl4-induced hepatic fibrosis（HF）and its mechanism. MethodsA total of 56 male SD rats were randomly divided into seven groups： normal group（NG），model group（MG），colchicine group（CG， 0.1 mg/kg）， Fuzheng Huayu group（FG， 0.45 g/kg），low-dose DOP group（LDG， 0.05 g/kg），middle-dose DOP group（MDG， 0.1 g/kg）and high-dose DOP group（HDG，0.2 g/kg），with 8 rats in each group. HF rat model was established by subcutaneous injection with 40% CCl4 olive oil mixture， every 3-day for 10 weeks. At the end of the sixth week， the drug groups were treated with colchicine， Fuzheng Huayu and DOP solution by gavage respectively， once a day for 4 weeks. NG and MG groups were similarly handled with an equal amount of 0.9 % normal saline. Liver histopathology was detected using hematoxylin-eosin （HE）， Masson and Sirius red staining； blood biochemistry was tested for liver function and four indicators of HF； RT-qPCR and Western Blot were used to measure the expression of α-SMA， Col-I， E-cadherin， and ZEB1 genes and proteins in the liver tissues of rats， respectively. ResultsHE， Masson， and Sirius red staining showed that the liver tissue of MG rats had typical pathologic features of HF， and the degree of HF was alleviated in LDG， MDG， and HDG rats， respectively. Liver function test results showed that the serum AST， TBIL， and AKP levels were significantly lower in LDG， MDG， and HDG， compared with those of the MG （P < 0.05 or < 0.01）. Meanwhile， ALT levels in serum deceased remarkably except in LDG （P < 0.05 or < 0.01）. The four results of HF showed that the serum HA， LN， PC-Ⅲ， and COL-Ⅳ levels in LDG， MDG， and HDG rats were significantly decreased compared with those of the MG （P < 0.05 or < 0.01）. The relative expressions of α-SMA， COL-I， and ZEB1 genes and proteins were significantly decreased in the liver tissues of LDG， MDG， and HDG （P < 0.05 or < 0.01）， and the relative expression of E-cadherin gene and protein increased （P < 0.05 or < 0.01）. In addition， the expressions of HA， α-SMA， COL-I， ZEB1 and E-cadherin were dependent on the dose of DOP. ConclusionDOP alleviated the degree of CCl4 induced HF in rats by inhibiting the epithelial-mesenchymal transition in liver tissue.
ABSTRACT
Objective To investigate the correlation of Wnt5a expression and vasculogenic mimicry (VM) in prostate cancer tissues, and analyze their relationships with cancer stem cells (CSCs) characteristics and epithelial–mesenchymal transition (EMT). Methods Immunohistochemistry was conducted to detect the expression of Wnt5a in 50 prostate cancer tissues and 50 benign prostatic hyperplasia tissues. The expression levels of CD133, vimentin, and E-cadherin were detected in the prostate cancer tissues, and CD34/PAS double staining was used to detect VM structures. We analyzed the difference in Wnt5a level between prostate cancer and benign prostatic hyperplasia tissues, the clinical significance of Wnt5a and VM, the relationship of Wnt5a expression and VM, and the relationships of Wnt5a expression and VM with CD133, Vimentin, E-cadherin. Results The expression of Wnt5a was significantly higher in prostate cancer tissues than in benign prostatic hyperplasia (P < 0.05). A positive correlation was observed between Wnt5a expression and VM (P < 0.05). The expression levels of Wnt5a and VM were positively correlated with those of CD133 and vimentin (P < 0.05). Wnt5a expression and VM were positively correlated with Gleason score, vas deferens invasion and lymphatic metastasis (P < 0.05) of prostate cancer, and VM was also positively correlated with T stage of prostate cancer (P < 0.05). Conclusion The expression level of Wnt5a in prostate cancer tissues is elevated and positively related with VM formation. Wnt5a expression and VM are correlated with cancer stem cells characteristics and the expression of epithelial–mesenchymal transition marker proteins.
ABSTRACT
OBJECTIVE To investigate the effects of anlotinib on the malignant phenotype of glioma cells by regulating the nuclear factor-κB （NF-κB） signaling pathway. METHODS Human glioma T98G cells were cultured in vitro， and 5-fluorouracil was used as positive control to investigate the effects of different concentrations of anlotinib （5， 10， 20 μmol/L） on the ability of proliferation， adhesion， migration and invasion， the expressions of epithelial-mesenchymal transition （EMT） related proteins [E-cadherin， N-cadherin， vimentin and fibronectin （FN）]. NF- κB signaling pathway inhibitor （BAY 11-7082） and activator （prostratin） were additionally used to verify the possible mechanism of the above effects of anlotinib. RESULTS Anlotinib with 5， 10， 20 μmol/L could significantly decrease the activity of cell proliferation （except for 5 μmol/L anlotinib group）， migration rate， and the number of adherent cells and invasive cells， could significantly up-regulate the expression of E-cadherin protein while down-regulate the expressions of N-cadherin， vimentin and FN protein （P＜0.05）； the effect of 20 μmol/L anlotinib was similar to that of positive control （P＞0.05）. Compared with 10 μmol/L anlotinib， pathway inhibitor could significantly decrease the ability of proliferation， adhesion， migration and invasion， and the expressions of N-cadherin， vimentin， FN and phosphorylated NF-κB p65 protein， while could significantly up-regulate the expression of E-cadherin protein （P＜0.05）； above indexes were reversed significantly by pathway activator （P＜0.05）. CONCLUSIONS Anlotinib may inhibit the proliferation， adhesion， migration and invasion of human glioma T98G cells， which may be associated with the inhibition of the NF-κB signaling pathway， thus inhibiting cell EMT-like processes.
ABSTRACT
ObjectiveBy observing the effect of Qianyang Yuyin granules on the phenotype of renal tubule epithelial cells， the intervention of Qianyang Yuyin granule on renal interstitial fibrosis was investigated. MethodThe renal tubular epithelial cells （HK-2） were treated with different concentrations of transforming growth factor （TGF）-β1 （5， 10， 15， 20， 25 μg·L-1） for 24 hours， and cell morphology and growth state were observed with an inverted phase contrast microscope. The 20 μg·L-1 was selected as the most appropriate concentration of TGF-β1 according to Western blot results for subsequent experiments. HK-2 cells were divided into six groups： blank group， TGF-β1 group （concentration of 20 μg·L-1）， low， medium， and high dose Qianyang Yuyin granule groups （concentration of 0.5， 1， 2 g·L-1）， and valsartan group （1 × 10-5 mol·L-1）. The cell activity was measured by cell proliferation and cell counting kit-8 （CCK-8）. The cell migration ability was detected by scratch test. The Transwell method was used to detect the invasiveness of cells. Western blot was used to detect levels of fibronectin （FN）， E-cadherin， α-smooth muscle activator （α-SMA）， Vimentin， collagen type Ⅰ（Col Ⅰ）， collagen type Ⅳ（Col Ⅳ）， and other related proteins. ResultTGF-β1 stimulating epithelial-mesenchymal transition （EMT） in renal tubular epithelial cells was time- and concentration-dependent. Compared with the blank group， higher concentration in the TGF-β1 group indicates longer intervention time and more obvious long spindle change of cells， and the migration and invasion ability of the cells was significantly enhanced. The protein expression level of FN， α-SMA， Vimentin， Col Ⅰ， and Col Ⅳ increased significantly （P<0.05， P<0.01）， while the expression level of E-cadherin protein decreased （P<0.05）. Compared with the TGF-β1 group， Qianyang Yuyin granule groups could maintain normal cell morphology， and the migration and invasion ability of the cells was inhibited. The protein expression level of FN， α-SMA， Vimentin， Col Ⅰ， and Col Ⅳ decreased （P<0.05， P<0.01）， and the expression of E-cadherin protein was significantly restored （P<0.05）. ConclusionQianyang Yuyin granule can reverse TGF-β1-induced interstitial transformation of renal tubular epithelial cells by reducing the phenotypic expression of mesenchymal cells and increasing the phenotypic expression of epithelial cells.
ABSTRACT
O objetivo do estudo foi avaliar a qualidade do sono e sonolência diurna de um grupo de idosos, verificar se há associação com prática de atividade física, presença de doença crônica, e Índice de Massa Corporal (IMC) e se há correlação com IMC, idade e qualidade de vida. Trata-se de um estudo transversal e descritivo. Para avaliação da qualidade do sono utilizou-se o Pittsburgh Sleep Quality Index (PSQI), para avaliação da sonolência diurna a Escala de Sonolência de Epworth (ESE) e para avaliação da qualidade de vida o WHOQOL-BREF. Foram avaliados 47 idosos com mediana (intervalo interquartil 25-75%) de 66 (62-70) anos de idade e IMC de 28,58 (26,21-30,44). 74,5% apresentaram sono ruim, 61,7% apresentaram Sonolência Diurna Normal e 97,8% classificados com boa qualidade de vida, com destaque para os domínios relações sociais (80%) e autoavaliação da qualidade de vida (80%). Apenas apresentou associação estatisticamente significativa a presença de qualidade de sono ruim com a prática de atividade física. Não houve associação entre presença de qualidade de sono ruim ou sonolência com IMC e presença de doença crônica. Houve uma correlação fraca, negativa e estatisticamente significativa apenas entre qualidade do sono com qualidade de vida (ρ=-0,466) e idade (ρ=-0,297). Conclui-se que os idosos apresentaram qualidade do sono ruim, sonolência diurna normal e qualidade de vida geral boa.
The objective of the study was to evaluate the quality of sleep and daytime sleepiness of a group of elderly people, checking whether there is an association with physical activity, presence of chronic disease, and Body Mass Index (BMI) and whether there is a correlation with BMI, age and quality of life. This is a cross-sectional and descriptive study. To assess sleep quality, the Pittsburgh Sleep Quality Index (PSQI) was used, the Epworth Sleepiness Scale (ESE) was used to assess daytime sleepiness, and the WHOQOL-BREF was used to assess quality of life. 47 elderly people were evaluated with a median (interquartile range 25-75%) of 66 (62-70) years of age and BMI of 28.58 (26.21-30.44). 74.5% had poor sleep, 61.7% had Normal Daytime Sleepiness and 97.8% classified as having a good quality of life, with emphasis on the domains of social relationships (80%) and self-assessment of quality of life (80%). There was only a statistically significant association between the presence of poor sleep quality and the practice of physical activity. There was no association between the presence of poor sleep quality or sleepiness with BMI and the presence of chronic disease. There was a weak, negative and statistically significant correlation only between sleep quality and quality of life (ρ=-0.466) and age (ρ=- 0.297). It is concluded that the elderly had poor sleep quality, normal daytime sleepiness and good general quality of life.
ABSTRACT
Introduction: The lack of knowledge on seed germination and seedling establishment is a main constraint for the restoration of degraded areas, including the tropical dry forest known as Caatinga. Objective: To assess reserve and secondary metabolite mobilization during seed germination and seedling establishment in Erythina velutina. Methods: We scarified, disinfected, imbibed, sown between towel paper, and incubated seeds under controlled conditions. We hydroponically cultivated seedlings in a greenhouse. We harvested cotyledons at seed imbibition, radicle protrusion, hypocotyl emergence, apical hook formation and expansion of cordiform leaves, first trifoliate leaf, and second trifoliate leaf. Results: Seeds contained approximately 20 % starch, 14.5 % storage proteins, 11.6 % neutral lipids, and 5.7 % non-reducing sugars on a dry weight basis. Soluble sugars were mainly consumed from hypocotyl emergence to apical hook formation, while major reserves were mobilized from apical hook formation to expansion of first trifoliate leaf. Enzymatic activity increased from mid to late seedling establishment, causing the mobilization of starch, oils, and proteins. Terpenoid-derivatives, flavonoids, phenolic acids, and alkaloids were detected. Flavonoids and phenolic acids were present at almost all stages and terpenoid-derivatives disappeared at expansion of cordiform leaves. Conclusion: Soluble sugars support early seedling growth, while starch, oils and proteins are simultaneously mobilized from mid to late establishment by amylases, lipases, and acid proteases. The cotyledons contain secondary metabolites, which may act in seedling defense. High content of reserves and presence of secondary metabolites in the cotyledons could enable E. velutina seedlings endure stress, validating their use in the restoration of degraded areas.
Introducción: La falta de conocimiento sobre la germinación de semillas y el establecimiento de plántulas es una de las principales limitaciones para la restauración de áreas degradadas, incluido el bosque seco tropical conocido como Caatinga. Objetivo: Evaluar la movilización de reservas y metabolitos secundarios durante estas etapas de desarrollo en Erythina velutina. Métodos: Las semillas fueron escarificadas, desinfectadas, embebidas, sembradas entre toallas de papel e incubadas bajo condiciones controladas. Cultivamos las plántulas hidropónicamente en un invernadero. Recolectamos los cotiledones en la imbibición de la semilla, la protrusión de la radícula, la emergencia del hipocótilo, la formación del gancho apical y la expansión de las hojas cordiformes, la primera y segunda hoja trifoliada. Resultados: Las semillas contenían 20 % de almidón, 14.5 % de proteínas de almacenamiento, 11.6 % de lípidos neutros y 5.7 % de azúcares no reductores en peso seco. Los azúcares solubles se consumieron desde la emergencia del hipocótilo hasta la formación del gancho apical. Las principales reservas se movilizaron desde la formación del gancho apical hasta la expansión de la primera hoja trifoliada. La actividad enzimática aumentó desde la mitad hasta el final del establecimiento de las plántulas, movilizando almidón, aceites y proteínas. Se detectaron derivados de terpenoides, flavonoides, ácidos fenólicos y alcaloides. Los flavonoides y los ácidos fenólicos estuvieron en casi todas las etapas y los derivados terpenoides desaparecieron en la expansión de las hojas cordiformes. Conclusión: Los azúcares solubles apoyan el crecimiento temprano de las plántulas; el almidón, los aceites y las proteínas se movilizan simultáneamente desde el establecimiento medio hasta el final por amilasas, lipasas y proteasas ácidas. Los cotiledones contienen metabolitos secundarios, que pueden actuar en la defensa de las plántulas. El alto contenido de reservas y los metabolitos secundarios en los cotiledones podría permitir que las plántulas de E. velutina toleren estrés, validando su uso en la restauración de áreas degradadas.
Subject(s)
Germination , Erythrina , Environmental Restoration and Remediation/methods , Fabaceae , BrazilABSTRACT
Abstract Background: Surgeons create a neorectum to repair patients with Hirschsprung´s disease (HD), which should be formed from a normoganglionic bowel. However, the neorectum is occasionally created with a transition zone (TZ) bowel. A neorectum created with a TZ has been postulated as a cause of postoperative enterocolitis or constipation. This study compares the incidence of enterocolitis and constipation in patients with TZ neorectum and normoganglionic bowel. Methods: We conducted a retrospective review of patients with rectosigmoid HD who underwent primary pull-through. Patients were divided into normoganglionic neorectum (NNR) and TZ neorectum. The diagnosis was based on the final histopathologic report of the proximal margin. The incidence of enterocolitis and constipation was compared between these two groups. Results: A total of 98 HD patients were analyzed. Seventy-one patients fulfilled the inclusion criteria. 65 (92%) had a NNR, and six patients (8%) had a TZ neorectum. From these patients, 42 (59%) presented with enterocolitis or constipation. However, there was no significant difference between both groups. Conclusion: The present study showed no difference in the incidence of enterocolitis or postoperative constipation in HD patients with normoganglionic or TZ neorectum. These results suggest that TZ neorectum does not cause postoperative obstructive symptoms.
Resumen Introducción: Los cirujanos crean un neo-recto para tratar a los pacientes con enfermedad de Hirschsprung (EH), que debe formarse con intestino normogangliónico; sin embargo, en ocasiones el neo-recto se forma con intestino de la zona de transición. Se ha postulado que un neo-recto en zona de transición causa enterocolitis o estreñimiento postoperatorio. El objetivo de este estudio fue comparar la frecuencia de enterocolitis y estreñimiento en pacientes con neo-recto en zona de transición y con neo-recto normogangliónico. Métodos: Se llevó a cabo una revisión retrospectiva de pacientes con EH recto sigmoideo que se sometieron a descenso primario. Los pacientes se dividieron en el grupo neo-recto normogangliónico y el grupo con neo-recto en zona de transición. El diagnóstico del neo-recto se estableció con el informe histopatológico definitivo del margen proximal. Se comparó la frecuencia de enterocolitis y estreñimiento entre estos dos grupos. Resultados: Se analizó un total de 98 pacientes con EH, de los cuales 71 pacientes cumplieron los criterios de inclusión; 65 (92%) con neo-recto normogangliónico y seis (8%) con neo-recto en zona de transición. Posteriormente, 42 (59%) pacientes presentaron enterocolitis asociada a Hirschsprung (HAEC) o estreñimiento; sin embargo, no hubo diferencia significativa entre ambos grupos. Conclusiones: El presente estudio no demostró una diferencia en la frecuencia de HAEC o estreñimiento postoperatorio en pacientes con EH con neo-recto normogangliónico o en zona de transición. Estos resultados sugieren que un neo-recto en zona de transición no causa síntomas obstructivos postoperatorios.
ABSTRACT
Os pacientes oncológicos necessitam de uma assistência integral, sobretudo no que se refere à transição do cuidado em saúde entre os diferentes locais e níveis de cuidado. Este estudo tem como objetivo investigar se existem protocolos assistenciais utilizados pela equipe interprofissional sobre a transição do cuidado oncológico hospitalar para o domicílio e identificar as estratégias utilizadas no planejamento e orientações da alta hospitalar. Trata-se de um estudo descritivo de abordagem qualitativa, realizado através de Grupo Focal, com profissionais da equipe interprofissional que atuam diretamente com o cuidado oncológico, em hospital filantrópico, localizado no interior do Estado do Rio Grande do Sul. Construíram-se categorias que elencaram as principais características: Desafios na transição do cuidado para a rede de atenção primária e domiciliar e Sugestões para a mudança nas intervenções do cuidado integrado em oncologia. Constatou-se que a equipe interprofissional apresenta dificuldades na compreensão sobre a transição do cuidado e a necessidade de uma maior quantitativo de colaboradores para a qualificação da assistência.(AU)
Cancer patients need comprehensive care, especially with regard to the transition of health care between different locations and levels of care. This study aims to investigate whether there are care protocols used by the interprofessional team on the transition from hospital to home oncology care and to identify the strategies used in hospital discharge planning and guidance. This is a descriptive study with a qualitative approach, carried out through focus groups with professionals from the interprofessional team who work directly with cancer care in a philanthropic hospital located in the interior of the state of Rio Grande do Sul. Categories were constructed which listed the main characteristics: Challenges in the transition of care to the primary and home care network and Suggestions for change in integrated oncology care interventions. It was found that the interprofessional team has difficulties in understanding the transition of care and the need for a greater number of collaborators to improve care.(AU)
Los pacientes oncológicos requieren una atención integral, especialmente en lo que se refiere a la transición de la asistencia sanitaria entre diferentes lugares y niveles asistenciales. Este estudio pretende investigar si existen protocolos asistenciales utilizados por el equipo interprofesional en la transición de la atención oncológica hospitalaria a la domiciliaria e identificar las estrategias utilizadas en la planificación y guías de alta hospitalaria. Se trata de un estudio descriptivo con abordaje cualitativo, realizado a través de grupos focales con profesionales del equipo interprofesional que trabajan directamente con la atención oncológica en un hospital filantrópico localizado en el interior del estado de Rio Grande do Sul. Se construyeron categorías que enumeraron las principales características: Desafíos en la transición de la atención a la red de atención primaria y domiciliaria y Sugerencias de cambio en las intervenciones de atención oncológica integrada. Se encontró que el equipo interprofesional tiene dificultades en la comprensión de la transición de la atención y la necesidad de un mayor número de colaboradores para mejorar la atención.(AU)