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1.
Artigo em Inglês | MEDLINE | ID: mdl-38597324

RESUMO

Purpose: The study aims to explore the roles and underlying mechanisms of long noncoding RNAs endogenous bornavirus-like nucleoprotein (lncRNA EBLN3P) in colon cancer, emphasizing the potential impact of these insights on advancing colon cancer treatment strategies. By shedding light on lncRNA EBLN3P's involvement, this research could contribute to the development of novel therapeutic approaches, enhancing the efficacy of interventions for colon cancer patients. Methods: We employed quantitative reverse transcription polymerase chain reaction to assess the levels of lncRNA EBLN3P, zinc finger protein (ZFP91), and miR-519d-3p, alongside CCK-8 and EdU assays for cell proliferation, flow cytometry for apoptosis, and Transwell and wound healing assays for migration and invasion. The in vivo function of lncRNA EBLN3P was investigated through a xenograft model, and protein levels were evaluated via Western blot analysis. Results: LncRNA EBLN3P was found to be upregulated in colon cancer tissues and cells, promoting cell proliferation and metastasis while inhibiting apoptosis. Downregulation of lncRNA EBLN3P reduced tumor size, volume, and weight in a mouse model. MiR-519d-3p, which negatively interacts with lncRNA EBLN3P, was found to be downregulated in colon cancer tissues and cell lines. Its upregulation hindered cancer cell proliferation and metastasis while enhancing apoptosis. ZFP91, a binding partner of miR-519d-3p, was upregulated in colon cancer and inversely related to miR-519d-3p levels. Rescue experiments indicated that the effects of lncRNA EBLN3P silencing could be reversed by miR-519d-3p suppression, but were mitigated by ZFP91 downregulation. Conclusion: LncRNA EBLN3P facilitates colon cancer progression via the miR-519d-3p/ZFP91 axis, presenting a novel understanding of lncRNA EBLN3P's role and offering potential therapeutic insights for colon cancer treatment. This study fills a critical gap by linking lncRNA EBLN3P with the miR-519d-3p/ZFP91 axis in the context of colon cancer, thereby broadening our understanding of the molecular mechanisms underlying colon cancer progression.

2.
Exp Cell Res ; 437(1): 113994, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38479704

RESUMO

m6A modification has been studied in tumors, but its role in host anti-tumor immune response and TAMs polarization remains unclear. The fatty acid oxidation (FAO) process of TAMs is also attracting attention. A co-culture model of colorectal cancer (CRC) cells and macrophages was used to simulate the tumor microenvironment. Expression changes of m6A demethylase genes FTO and ALKBH5 were screened. ALKBH5 was further investigated. Gain-of-function experiments were conducted to study ALKBH5's effects on macrophage M2 polarization, CRC cell viability, proliferation, migration, and more. Me-RIP and Actinomycin D assays were performed to study ALKBH5's influence on CPT1A, the FAO rate-limiting enzyme. AMP, ADP, and ATP content detection, OCR measurement, and ECAR measurement were used to explore ALKBH5's impact on macrophage FAO level. Rescue experiments validated ALKBH5's mechanistic role in macrophage M2 polarization and CRC malignant development. In co-culture, CRC cells enhance macrophage FAO and suppress m6A modification in M2 macrophages. ALKBH5 was selected as the gene for further investigation. ALKBH5 mediates CPT1A upregulation by removing m6A modification, promoting M2 macrophage polarization and facilitating CRC development. These findings indicate that ALKBH5 enhances fatty acid metabolism and M2 polarization of macrophages by upregulating CPT1A, thereby promoting CRC development.


Assuntos
Neoplasias Colorretais , Macrófagos , Humanos , Regulação para Cima/genética , Macrófagos/metabolismo , Neoplasias Colorretais/patologia , Ácidos Graxos/metabolismo , Microambiente Tumoral , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Homólogo AlkB 5 da RNA Desmetilase/genética , Homólogo AlkB 5 da RNA Desmetilase/metabolismo
3.
Chin J Integr Med ; 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37222828

RESUMO

OBJECTIVE: To clarify the potential mechanism of Banxia Xiexin Decoction (BXD) on colorectal cancer (CRC) from the perspective of metabolomics. METHODS: Forty male C57BL/6 mice were randomly divided into normal control (NC), azoxymethane/dextran sulfate sodium (AOM/DSS) model, low-dose BXD (L-BXD), high-dose BXD (H-BXD) and mesalamine (MS) groups according to a random number table, 8 mice in each group. Colorectal cancer model was induced by AOM/DSS. BXD was administered daily at doses of 3.915 (L-BXD) and 15.66 g/kg (H-BXD) by gavage for consecutive 21 days, and 100 mg/kg MS was used as positive control. Following the entire modeling cycle, colon length of mice was measured and quantity of colorectal tumors were counted. The spleen and thymus index were determined by calculating the spleen/thymus weight to body weight. Inflammatory cytokine and changes of serum metabolites were analyzed by enzyme-linked immunosorbent assay kits and ultra performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q/TOF-MS), respectively. RESULTS: Notably, BXD supplementation protected against weight loss, mitigated tumor formation, and diminished histologic damage in mice treated with AOM/DSS (P<0.05 or P<0.01). Moreover, BXD suppressed expression of serum inflammatory enzymes, and improved the spleen and thymus index (P<0.05). Compared with the normal group, 102 kinds of differential metabolites were screened in the AOM/DSS group, including 48 potential biomarkers, involving 18 main metabolic pathways. Totally 18 potential biomarkers related to CRC were identified, and the anti-CRC mechanism of BXD was closely related to D-glutamine and D-glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arginine biosynthesis, nitrogen metabolism and so on. CONCLUSION: BXD exerts partial protective effects on AOM/DSS-induced CRC by reducing inflammation, protecting organism immunity ability, and regulating amino acid metabolism.

4.
Biosci Rep ; 43(5)2023 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-36951135

RESUMO

Colorectal cancer (CRC) ranks third and second among the most widespread cancers worldwide and the most common causes of human death due to cancer, respectively. Furthermore, for unknown reasons, numbers of young patients diagnosed with colon cancer has increased. Polysaccharides are important functional phytochemicals reported to have anti-CRC effects. Moreover, CRC development and progression is closely related to the gut microbiome. Although approaches for treating CRC have been the subject of some review papers, research into traditional Chinese medicine (TCM) treatments for CRC and the underlying mechanisms involving polysaccharides have not been reviewed. Here, we reviewed the mechanisms underlying treatment of CRC using TCM polysaccharides, based on the etiology of CRC, and common treatment methods applied. The relationship between intestinal microbes and CRC, the mechanism by which TCM polysaccharides induce CRC cell apoptosis, and how TCM polysaccharides promote immune responses are discussed, as well as TCM polysaccharide use in combination with chemotherapy. TCM polysaccharides provide options for CRC treatment, due to their advantages of having multiple targets, eliciting modest adverse reactions, and wide range of available sources.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Medicamentos de Ervas Chinesas , Humanos , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/diagnóstico , Antineoplásicos/efeitos adversos , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico
5.
Front Chem ; 9: 675346, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33937209

RESUMO

Antioxidation is very important in medicine and food. The current evaluation technologies often have many shortcomings. In this work, an improved electrochemical sensing platform for the evaluation of antioxidant activity has been proposed. A hydrogel was prepared based on graphene oxide, zinc ions, and chitosan. Zinc ions play the role of crosslinking agents in hydrogels. The structure of chitosan can be destroyed by injecting hydrogen peroxide into the hydrogel, and the free zinc ions can diffuse to the surface of the electrode to participate in the electrochemical reaction. This electrochemical sensor can evaluate the antioxidant activity by comparing the current difference of zinc reduction before and after adding the antioxidant. With the help of graphene oxide, this hydrogel can greatly enhance the sensing effect. We conducted tests on 10 real samples. This proposed electrochemical platform has been successfully applied for evaluating the antioxidant activity of Scutellaria baicalensis, and the results were compared to those obtained from the 2,2-diphenyl-1-picrylhydrazyl-based traditional analysis technique.

6.
Ann Palliat Med ; 9(5): 2837-2852, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32921064

RESUMO

BACKGROUND: In China, Zhishi (Aurantii Fructus Immaturus) - Baizhu (Atractylodis Macrocephalae Rhizoma) is a well-known herb pair used to treat gastrointestinal motility disorders for thousands of years, and it has especially shown a definite advantage in the treatment of slow transit constipation (STC). However, the mechanism of Zhishi-Baizhu (ZSBZ) in the treatment of STC remains unclear. In this study, plasma metabolomics research combined with metabolic pathway analysis has been used to illuminate the potential mechanism of its effects against STC. METHODS: Parameters of intestinal transit ratio, plasma motilin (MTL), substance P (SP), adenosine triphosphate (ATP), histological alteration of the colon and MLCK expression in the colon were detected to evaluate the effects with respect to STC. Principal component analysis (PCA) was used to investigate the global metabolite alterations, while orthogonal partial least squares discriminant analysis (OPLS-DA) and t-test were used to filter potential metabolite markers. Moreover, metabolic pathway analysis was employed. RESULTS: Oral administration of ZSBZ significantly prevented the development of STC. It increased the expression of MTL and SP in serum, as well as the expression of ATP and MLCK in the colon. ZSBZ administration alleviated symptoms in loperamide-induced constipated rats, evidenced by the increase of intestinal transit ratio. Futhermore, 9 potential biomarkers of STC were screened, and the levels were all reversed to different degrees after ZSBZ administration. Metabolic pathway analysis showed that the improvement of STC by ZSBZ was mainly related to caffeine and vitamin B6 metabolism. CONCLUSIONS: Our study identifies the metabolic networks of constipated rats and demonstrates the efficacy of this metabolomics approach to systematically study the therapeutic effects of ZSBZ on constipation.


Assuntos
Atractylodes , Animais , China , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/tratamento farmacológico , Medicamentos de Ervas Chinesas , Metabolômica , Ratos
7.
Ann Palliat Med ; 9(5): 2826-2836, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32787366

RESUMO

BACKGROUND: Geniposide (GE) is the main component in gardenia fruit. This study aimed to investigate the protective effects and potential mechanisms of GE on dextran sulfate sodium (DSS)-induced colitis in mice and lipopolysaccharide (LPS)-induced RAW 264.7 cells. METHODS: The in vivo acute colitis experimental model was established by administering drinking water containing 3% DSS to the mice for 7 days. GE was administered to the mice via oral gavage at 20 and 40 mg/kg for 7 days. Colon length, colon myeloperoxidase (MPO) level, serum and colon malondialdehyde (MDA) levels, and superoxide dismutase (SOD) activity were determined, and histological evaluation was performed. The levels of interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α (TNF-α) in the serum and colon were detected. The expression of proteins of the nuclear factor E2 related factor 2 (Nrf-2)/HO-1/ NF-κB pathway in the colon was detected. The in vitro model of LPS-induced RAW 264.7 cells to simulate enteritis model. Cell viability, IL-6, IL-1ß, and TNF-α levels in the cell supernatant were measured. The MPO levels in RAW 264.7 cells and DSS-induced mice and MDA and SOD levels in the cell supernatant were measured. The expression of proteins of the Nrf-2/HO-1/NF-κB pathway in RAW 264.7 cells was determined. RESULTS: GE treatment resulted in significant histological changes and reduced the expression of inflammatory mediators IL-6, IL-1ß, and TNF-α the in serum, colon, and cell supernatant effectively. Parenteral nutrition reduced MPO content in the colon and RAW 264.7 cells. GE treatment increased SOD levels in the serum, colon, and cell supernatant. GE restored the protein expression of the Nrf-2/HO-1/ NF-κB pathway in RAW 264.7 cells and nude mice, and these changes were blocked significantly by Nrf-2 siRNA. CONCLUSIONS: These findings demonstrated that GE ameliorated inflammation and oxidative stress in experimental colitis via modulation of the Nrf-2/HO-1/NF-κB pathway. Thus, GE could serve as a potential therapeutic agent for the treatment of ulcerative colitis (UC).


Assuntos
Colite , NF-kappa B , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Sulfato de Dextrana/toxicidade , Iridoides , Camundongos , Camundongos Nus , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais
8.
J Integr Med ; 18(4): 334-343, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32532614

RESUMO

OBJECTIVE: To investigate the effects of Aurantii Fructus Immaturus (Zhishi, ZS) and Atractylodis Macrocephalae Rhizoma (Baizhu, BZ)-containing serum on glutamate-induced autophagy in rat colonic interstitial cells of Cajal (ICCs) and to analyze the underlying mechanism. METHODS: Rat colonic ICCs cultured in vitro were identified by fluorescence and then stimulated with glutamic acid (5 mmol/L) for 24 h to establish a cell model of autophagy. The cells were then treated with different concentrations of ZSBZ-containing serum or rat serum. The viability of the ICCs was detected with cell counting kit-8 assays, and cell apoptosis rates were examined with flow cytometry. The ultrastructure and autophagosomes in the ICCs were observed using transmission electron microscopy. The effects of ZSBZ-containing serum on apoptosis-associated mediators were assessed by Western blotting and real-time quantitative polymerase chain reaction. In addition, microtubule-associated protein light chain 3 (LC3), p-phosphoinositide 3-kinase (p-PI3K), p-Akt and p-mammalian target of rapamycin (p-mTOR) expression was detected via Western blotting analysis. RESULTS: Compared to those in the model group, ICC viability and apoptosis rates were significantly increased by ZSBZ-containing serum (P < 0.05). In addition, the expression levels of Beclin-1, LC3, p-PI3K, p-Akt and p-mTOR were significantly lower (P < 0.05) and Bcl-2 expression was higher in the ZSBZ-containing serum treatment groups than in the model group (P < 0.05). CONCLUSION: Our findings demonstrated that ZSBZ protects glutamic acid-stimulated ICCs, and this beneficial effect may be mediated by a reduction in autophagy via inhibition of the PI3K/Akt/mTOR pathway.


Assuntos
Atractylodes/química , Autofagia , Medicamentos de Ervas Chinesas/farmacologia , Células Intersticiais de Cajal , Animais , Apoptose , Ácido Glutâmico , Células Intersticiais de Cajal/efeitos dos fármacos , Células Intersticiais de Cajal/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Proteína Oncogênica v-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Ratos , Rizoma/química , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
9.
Ann Transl Med ; 7(16): 375, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31555689

RESUMO

BACKGROUNDS: Banxia Xiexin decoction (BXD) is widely used in the treatment of acute and chronic gastritis, peptic ulcer, dyspepsia, gastrointestinal dysfunction, chronic hepatitis, oral ulcer and other diseases, but there are few reports on its treatment of colon cancer. The current study was designed to investigate the effect of BXD on colon cancer and its possible molecular mechanisms. METHODS: Fifty SPF BALB/c nude mice were selected to establish an animal model of colon cancer bearing nude mice. Establishment of nude mice intestinal cancer model by subcutaneous injection of intestinal cancer cells. Serum superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by commercial kits. Pro-inflammatory cytokines in serum were detected. Western blotting was used to demonstrate the expression levels of related apoptosis proteins, inflammation and oxidative stress proteins. RESULTS: Our results showed that BXD could decrease SOD and increased MDA in nude mice bearing tumors. BXD increased pro-inflammatory cytokines in serum in nude mice bearing tumors. Western blotting revealed that the protein expressions of Bax, Caspase-3, Caspase-9 were increased by different concentrations of BXD, while Bcl-2 was decreased. BXD also decreased Nrf-2 and HO-1, and increased the levels of MAPK/NF-κB pathway in tumor tissue. CONCLUSIONS: BXD has an obvious tumor inhibiting effect on SW 480 colon cancer transplanted tumor in nude mice via apoptotic pathway and MAPK/NF-κB pathway.

10.
Ann Transl Med ; 7(16): 379, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31555693

RESUMO

BACKGROUND: Postoperative abdominal adhesions formation is considered a significant clinical entity implicating the healing process following major pelvic and abdominal surgery, with serious clinical complications and need for substantial health care expenditures. However, setting a physical barrier between the damage site and the neighboring tissues is a convenient and highly valid way to minimize or prevent peritoneal adhesions. The present experimental study evaluated the preventive effect of ligustrazine nanoparticles nano spray (LNNS) on postoperative abdominal adhesion in rats and explored its mechanism. METHODS: Sixty male Sprague Dawley (SD) rats were randomly divided into sham operation group, control group, sodium hyaluronate group and low, medium, and high dose LNNS groups. All groups were prepared with abdominal adhesion models except for the sham operation group. The models were made by opening the abdominal cavity to and filing the serosa in ileocecal junction. The abdominal cavity of rats in the sham operation group were only opened and sutured. The wound surface of rats in the sodium hyaluronate group, low, medium, and high dose LNNS groups were sprayed with sodium hyaluronate gel (0.5 mL/kg) and LNNS (2.5, 5, and 10 mL/kg). Rats in each group were sacrificed 7 days later. Degree of adhesion was evaluated by naked eyes and the pathological sections were scored afterwards. The collagen synthesis in adhesion tissues was detected by Masson's trichrome stain, and the activities of reactive oxygen species (ROS), nitric oxide (NO), superoxide dismutase (SOD) and malondialdehyde (MDA) in peritoneal fluid were detected with the method of chromogenic substrate. Levels of TNF-α and IL-1ß in serum, and the protein levels of MCP-1 and MMP-9 in adhesion tissues were detected by ELISA and. immunohistochemistry respectively. RT-PCR and Western blot were utilized to identify the expression levels of Nrf2, heme-oxygenase-1, NQO1 mRNA and protein in adherent intestinal tissues. RESULTS: Compared with the control group, the incidence of postoperative abdominal adhesions decreased in the low, medium and high dose LNNS groups, while the expression of SOD in the peritoneal fluid significantly increased. The expression levels of ROS, MDA and NO were reduced remarkably (P<0.05), so were the expression levels of serum TNF-α and IL-1ß (P<0.01) and the expression of MCP-1 protein in adhesion tissues. The MMP-9 protein expression, and Nrf2, heme-oxygenase-1, NQO1 mRNA and protein expressions increased. CONCLUSIONS: LNNS with medium or high dose can significantly reduce the incidence of postoperative abdominal adhesions, the mechanism of which may be the activation of Nrf2/ARE pathway, resulting in the up-regulation of Nrf2, heme-oxygenase-1, NQO1 and mRNA expression, as well as the levels of TNF-α and IL-1ß in peripheral blood and the expression of MCP-1 protein in adhesion tissues. Meanwhile, the content of MMP-9 protein in adhesion tissues were raised, and oxidative stress and inflammatory response are released.

11.
Eur J Pharmacol ; 858: 172464, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31233752

RESUMO

Long intergenic non-coding RNA No.668 (LINC00668) is implicated in the development of various malignancies. However, the role of LINC00668 and underlying mechanism in colorectal cancer (CRC) remains totally unknown. The expression pattern of LINC00668 in CRC cells were determined by qRT-PCR. CCK-8, EdU incorporation, flow cytometry, Transwell, and wound-healing assays were run to evaluate the functions of LINC00668 in CRC cells. Bioinformatics analyses were used to identify the LINC00668-specific binding with miRNAs that were screened by RNA pull-down. RNA immunoprecipitation and luciferase gene report assay were performed to confirm the interaction between miR-188-5p and LINC00668 in CRC cells. LINC00668 was significantly upregulated in CRC tissues and cells. Knockdown of LINC00668 suppressed cell proliferation and migration potential and induced cell apoptosis, but inhibition of miR-188-5p which was predicted to bind with LINC00668 reversed these effects. Furthermore, USP47 was a direct target of miR-188-5p, and overexpression of USP47 attenuated LINC00668 knockdown-induced tumor suppressive effects in CRC cells. Conclusively, our findings demonstrated that lncRNA LINC00668 acted as an oncogenic role in CRC cells by sponging miR-188-5p and upregulating USP47 and may represent a potential marker for CRC patients.


Assuntos
Carcinogênese/genética , Progressão da Doença , MicroRNAs/genética , RNA Longo não Codificante/genética , Ubiquitina Tiolesterase/genética , Apoptose/genética , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Técnicas de Silenciamento de Genes , Humanos , Proteases Específicas de Ubiquitina
12.
Chin J Integr Med ; 25(7): 554-560, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30623344

RESUMO

Plants are known to possess plenty of pharmacological activities as a result of various phytoconstituents. Tetramethylpyrazine (TMP), one of the most widely used medicinal compound isolated from traditional Chinese herb, is usually employed for anti-oxidation, anti-inflammation, anti-platelet aggregation, anti-lipid, anti-fibrosis, as well as activating blood, removing stasis, dilating small arteries, improving microcirculation and antagonizing calcium. In the present paper, the anti-adhesion effect of TMP were reviewed. TMP was found to play a multi-target and muti-link role in anti-adhesion by inhibiting hyperplasia of collagen and overexpression of adhesion-related factors and reducing the concentration of white blood cells and fibrin in plasma. Because previous studies mostly focused on in vitro experiments and animal experiments, there is an urgent need for clinical research with abundant indicators to further prove its anti-adhesion potency. Future basic research should concentrate on the development of TMP as a biological material.


Assuntos
Reposicionamento de Medicamentos , Complicações Pós-Operatórias/tratamento farmacológico , Pirazinas/uso terapêutico , Aderências Teciduais/tratamento farmacológico , Animais , Ensaios Clínicos como Assunto , Humanos
13.
Acta Chir Belg ; 118(6): 372-379, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29482467

RESUMO

BACKGROUND: Postoperative peritoneal adhesions are a momentousness complication after abdominal surgery. Although varied means have been used to prevent and treat adhesions, the effects have not been satisfactory. Fluvastatin, a HMG-CoA reductase inhibitors, exhibits a variety of pharmacological effects. Aim of this study was to evaluate the effect of fluvastatin on postoperative peritoneal adhesion formation. METHODS: Seventy-five male Wistar rats weighting 220-250g were randomly assigned equally to three groups. Group A was given sham operation without treatment, Group B was the model group in which postoperative peritoneal adhesion model was created without medication, and Group C was given oral fluvastatin treatment after postoperative peritoneal adhesion model created. After laparotomy on day 7, macroscopic and pathological assessment were evaluated, IL-1ß and t-PA in plasma were performed to measure, and tissue samples were taken to measure MMP-9 protein. RESULTS: There were significant differences between the groups on adhesion grade (p < .05), IL-1ß content of the plasma and t-PA activity of the adhesions (p < .05). The grading of adhesion demonstrated significant differences between all groups. The levels of the IL-1ß content of plasma, t-PA activity and MMP-9 of adhesion showed pivotal changes in Group B compared with Group A and C, while the difference between Group A and C was not statistically significant. CONCLUSION: Oral fluvastatin application could reduce formation of intra-abdominal adhesion by promoting expression of MMP-9 level, lowering the levels of IL-1ß and increasing the activity of t-PA after abdominal surgery.


Assuntos
Fluvastatina/administração & dosagem , Laparotomia/efeitos adversos , Doenças Peritoneais/tratamento farmacológico , Aderências Teciduais/prevenção & controle , Cavidade Abdominal/cirurgia , Administração Oral , Animais , Biópsia por Agulha , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática/métodos , Imuno-Histoquímica , Laparotomia/métodos , Masculino , Doenças Peritoneais/etiologia , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/patologia , Distribuição Aleatória , Ratos , Ratos Wistar , Estatísticas não Paramétricas , Aderências Teciduais/etiologia , Aderências Teciduais/patologia , Resultado do Tratamento
14.
Chin J Integr Med ; 22(8): 629-34, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26424291

RESUMO

OBJECTIVE: To study the effect of ligustrazine nanoparticles nano spray (LNNS) on transforming growth factor ß (TGF-ß)/Smad signal protein of rat peritoneal mesothelial cells (RPMC) induced by tumor necrosis factor α (TNF-α), and the anti-adhesion mechanism of LNNS in the abdominal cavity. METHODS: The primary culture and subculture of rat peritoneal mesothelial cells (RPMC) was processed by trypsin digestion method in vitro. The third generation was identifified for experiment and divided into 5 groups: a blank group: RPMC without treatment; a control group: RPMC stimulated with TNF-α; RPMC treated by a low-dosage LNNS group (2.5 mg/L); RPMC treated by a medium-dosage LNNS group (5 mg/L); and RPMC treated by a high-dosage LNNS group (10 mg/L). Reverse transcription-polymerase chain reaction was applied to test the expression of fifibronectin, collagen I (COL-I), TGF-ß mRNA, and Western blot method to test the Smad protein 7 expression of RPMC. RESULTS: Compared with the blank group, a signifificant elevation in fifibronectin (FN), COL-I and TGF-ß mRNA expression of RPMC were observed in the control group (P<0.05). Compared with the control group, LNNS suppressed the expressions of FN, COL-I and TGF-ß mRNA in a concentrationdependent manner (P<0.05). The expression of Smad7 protein of RPMC was down-regulated by TNF-α stimulation, and up-regulated with the increase of LNNS dose (P<0.05). CONCLUSIONS: TNF-α may induce changes in RPMC's viability, leading to peritoneal injury. LNNS could reverse the induction of fifibrosis related cytokine FN, COL-I and TGF-ß, up-regulating the expression of Smad7 by TNF-α in RPMC, thus attenuate peritoneal injury by repairing mesothelial cells.


Assuntos
Epitélio/metabolismo , Nanopartículas/química , Cavidade Peritoneal/citologia , Pirazinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Animais , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Epitélio/efeitos dos fármacos , Fibronectinas/metabolismo , Masculino , Nanopartículas/ultraestrutura , Tamanho da Partícula , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta/genética
15.
J Obstet Gynaecol Res ; 41(12): 1942-50, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26419644

RESUMO

AIM: We aimed to evaluate the preventive effect of the ligustrazine nanoparticles nano spray (LNNS) for postoperative peritoneal adhesions in female rat models. MATERIAL AND METHODS: Fifty Wistar female rats weighting 250-300 g were randomly assigned to seven equal groups. All animals in the seven groups underwent midline laparotomy and ceca were abraded with sterile rasp. Group 1 underwent sham operations without treatment. In group 2, a postoperative peritoneal adhesion model was created, but no medication was given. In group 3, a postoperative peritoneal adhesion model was treated with LNNS, 2.5 mg/kg. In group 4, a postoperative peritoneal adhesion model was treated with LNNS, 5 mg/kg. In group 5, a postoperative peritoneal adhesion model was treated with LNNS, 10 mg/kg. In group 6, a postoperative peritoneal adhesion model was treated with polylactic acid (PLA) nanoparticle. In group 7, a postoperative peritoneal adhesion model was treated with ligustrazine, 2.5 mg/kg. Ten days after surgery, macroscopic and pathologic assessments were performed, and peritoneal fluid samples were collected in each group. The levels of tumor necrosis factor-α, tissue plasminogen activator and plasminogen activator inhibitor-1 in peritoneal fluid were determined by enzyme-linked immunosorbent assay. RESULTS: The adhesion score and extent of groups 4 and 5 was lower than that of group 2 in macroscopic assessment (P < 0.05). A comparison of tumor necrosis factor-α and tissue plasminogen activator level in the peritoneal fluid also demonstrated significant differences among groups 2, 4 and 5 (P < 0.05). The levels of plasminogen activator inhibitor-1 in peritoneal fluid in the LNNS groups were decreased compared to group 1. CONCLUSION: We suggest that LNNS could reduce peritoneal adhesion formation and it could be applied as a novel intervention for postoperative peritoneal adhesion.


Assuntos
Nanopartículas/administração & dosagem , Doenças Peritoneais/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Pirazinas/administração & dosagem , Aderências Teciduais/prevenção & controle , Animais , Líquido Ascítico/química , Ensaio de Imunoadsorção Enzimática , Feminino , Doenças Peritoneais/patologia , Inibidor 1 de Ativador de Plasminogênio/análise , Ratos , Ratos Wistar , Aderências Teciduais/patologia , Fator de Necrose Tumoral alfa/análise
16.
Pak J Pharm Sci ; 28(3 Suppl): 1049-54, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26051723

RESUMO

Adhesion-related complications after abdominal surgery bring out momentous morbidity and costs. Outcomes from animal experiments investigating prevention of adhesions are limited due to lack of consistency in existing animal models. Different intraperitoneal adhesion models were compared the inter observer variability was evaluated to seek for best model. Forty male SD rats weighting 250-300g were included and assigned randomly to four groups with diverse techniques, (A) postoperative adhesion cecum rat model abraded with sterile rasp; (B) postoperative adhesion cecum rat model abraded with sterile dry gauze; (C) postoperative adhesion cecum rat model abraded with sterile blade; (D) postoperative adhesion cecum rat model abraded with vascular clamp. Macroscopic adhesion scores were evaluated by Bigatti scoring system, and the incidence of adhesion were surveyed on the 7th day after the surgery. The results showed that four techniques currently used Bigatti adhesion scoring system are subjective, the sterile rasp is the most consistent and reproducible tool to establish an intraperitoneal adhesion model which is helpful for related studies and the development of new substances for adhesion prevention in the future.


Assuntos
Ceco/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Doenças Peritoneais/etiologia , Animais , Modelos Animais de Doenças , Masculino , Doenças Peritoneais/patologia , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Fatores de Tempo , Aderências Teciduais
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