RESUMO
Orodispersible films (ODFs) have emerged as an advanced and patient-friendly delivery system due to ease of administration, improved patient compliance, quick release and taste-masking of active pharmaceutical ingredients. This research reports the preparation of the ODF containing eugenol and borax (EB-ODF) by a solvent casting technique for treating mouth ulcers. The EB-ODF consisted of vinyl pyrrolidone/vinyl acetate copolymer (Kollidon® VA64, VA64) and hydroxypropyl methylcellulose (HPMC-K250) as the film formers where eugenol and borax were loaded. The thickness of the EB-ODF obtained was 0.119 ± 0.001 mm and the tensile strength was 13.1 ± 1.1 N/mm2 (p > 0.05). The prepared films disintegrated in the oral cavity within 30 s and over 90% of the eugenol was released from the film in the first 5 min. Furthermore, the combined application of eugenol and borax, loaded in EB-ODF, displayed notable synergetic antibacterial property against both gram-negative and gram-positive bacteria. In an in-vivo study on a rat model with chemical burn-induced oral ulcers, the EB-ODF treatment group had a 100% reduction in ulcer area (p > 0.05) after 10 days of treatment and demonstrated a 38.7% higher reduction in oral ulcer area compared to the Dingpeng Cream treatment group (p < 0.0001). The EB-ODF treatment group showed minimal oral irritation, scoring only 1 point and a 65% preference in the taste tests (p < 0.0001). In summary, EB-ODF had successfully overcome the poor palatability of commercially available formulation and provided notable potential for further ulcer treatment product development.
Assuntos
Boratos , Eugenol , Úlceras Orais , Eugenol/administração & dosagem , Eugenol/farmacologia , Animais , Ratos , Boratos/administração & dosagem , Úlceras Orais/tratamento farmacológico , Masculino , Administração Oral , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Derivados da Hipromelose/química , Ratos Wistar , Resistência à TraçãoRESUMO
Intestinal ischemia-reperfusion (IIR) injury is associated with inflammation and oxidative stress, yet its precise mechanisms remain not fully understood. IIR injury is closely linked to the gut microbiota and its metabolites. The anti-inflammatory and antioxidant effects of Lactiplantibacillus plantarum are specific to IIR. In our study, we conducted a 30-day pre-treatment of SD rats with both a standard strain of Lactiplantibacillus plantarum and Lactiplantibacillus plantarum GL001. After a 7-day cessation of treatment, we induced an IIR injury model to investigate the mechanisms by which Lactiplantibacillus plantarum alleviates IIR damage. The results demonstrate that Lactiplantibacillus plantarum effectively mitigates the inflammatory and oxidative stress damage induced by IIR. Lactiplantibacillus plantarum GL001 can improve the gut microbiota by reducing the abundance of harmful bacteria and increasing the abundance of beneficial bacteria. In IIR intestinal tissue, the levels of secondary bile acids are elevated. The content of the bacterial metabolite Calcimycin increases. Annotations of metabolic pathways suggest that Lactiplantibacillus plantarum GL001 can alleviate IIR damage by modulating calcium-phosphorus homeostasis through the regulation of parathyroid hormone synthesis, secretion, and action. Microbiota-metabolite correlation analysis reveals a significant negative correlation between calcimycin and Lactonacillus and a significant positive correlation between calcimycin and Shigella. There is also a significant positive correlation between calcimycin and secondary bile acids. Lactiplantibacillus plantarum GL001 can alleviate oxidative damage induced by IIR through improvements in gut microbiota and intestinal tissue metabolism.
Assuntos
Estresse Oxidativo , Traumatismo por Reperfusão , Ratos , Animais , Calcimicina/farmacologia , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Bactérias , Ácidos e Sais BiliaresRESUMO
BACKGROUND: Endoscopic ultrasonography (EUS) is recommended as the best tool for evaluating gastric subepithelial lesions (SELs); nonetheless, it has difficulty distinguishing gastrointestinal stromal tumors (GISTs) from leiomyomas and schwannomas. GISTs have malignant potential, whereas leiomyomas and schwannomas are considered benign. PURPOSE: This study aimed to establish a combined radiomic model based on EUS images for distinguishing GISTs from leiomyomas and schwannomas in the stomach. METHODS: EUS images of pathologically confirmed GISTs, leiomyomas, and schwannomas were collected from five centers. Gastric SELs were divided into training and testing datasets based on random split-sample method (7:3). Radiomic features were extracted from the tumor and muscularis propria regions. Principal component analysis, least absolute shrinkage, and selection operator were used for feature selection. Support vector machine was used to construct radiomic models. Two radiomic models were built: the conventional radiomic model included tumor features alone, whereas the combined radiomic model incorporated features from the tumor and muscularis propria regions. RESULTS: A total of 3933 EUS images from 485 cases were included. For the differential diagnosis of GISTs from leiomyomas and schwannomas, the accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve were 74.5%, 72.2%, 78.7%, and 0.754, respectively, for the EUS experts; 76.8%, 74.4%, 81.0%, and 0.830, respectively, for the conventional radiomic model; and 90.9%, 91.0%, 90.6%, and 0.953, respectively, for the combined radiomic model. For gastric SELs <20 mm, the accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve of the combined radiomic model were 91.4%, 91.6%, 91.1%, and 0.960, respectively. CONCLUSIONS: We developed and validated a combined radiomic model to distinguish gastric GISTs from leiomyomas and schwannomas. The combined radiomic model showed better diagnostic performance than the conventional radiomic model and could assist EUS experts in non-invasively diagnosing gastric SELs, particularly gastric SELs <20 mm.
Assuntos
Tumores do Estroma Gastrointestinal , Leiomioma , Neurilemoma , Neoplasias Gástricas , Humanos , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Tumores do Estroma Gastrointestinal/patologia , Endossonografia , Neoplasias Gástricas/diagnóstico por imagem , Leiomioma/diagnóstico por imagem , Leiomioma/patologia , Neurilemoma/diagnóstico por imagem , Estômago/patologiaRESUMO
BACKGROUND: During next generation sequencing (NGS) data interpretation in critically ill newborns, there is a potential for recognizing and reporting secondary findings (SFs). Early awareness of SFs may provide clues for disease prevention. In this study, we assessed the frequency of SFs in the China Neonatal Genomes Project (CNGP) participants. METHODS: A total of 2020 clinical exome sequencing (CES) datasets were screened for variants from a list of 59 genes recommended by the American College of Medical Genetics and Genomics (ACMG) for secondary findings reporting v2.0 (ACMG SF v2.0). Identified variants were classified according to the evidence-based guidelines reached by a joint consensus of the ACMG and the Association for Molecular Pathology (AMP). RESULTS: Among the 2020 CES datasets, we identified 23 ACMG-reportable genes in 61 individuals, resulting in an overall frequency of SFs at 3.02%. A total of 53 unique variants were identified, including 35 pathogenic and 18 likely pathogenic variants. The common disease categories of SFs associated were cardiovascular and cancer disease. The SF results affected the medical management and follow-up strategy in 49 (80.3%) patients. CONCLUSIONS: We presented the frequency of SFs and their impact on clinical management strategies in CNGP participants. Our study demonstrated that SFs have important practical value in disease prevention and intervention at an early stage.
Assuntos
Testes Genéticos , Neoplasias , Humanos , Recém-Nascido , Variação Genética , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
This study explored the effects of drinking Hydrogen-rich water (HRW) on skin wound healing in dogs. Eight circular wounds were analyzed in each dog. The experimental group was treated with HRW thrice daily, while the control group was provided with distilled water (DW). The wound tissues of dogs were examined histopathologically. The fibroblasts, inflammatory cell infiltration, the average number of new blood vessels, and the level of malondialdehyde (MDA) and superoxide dismutase (SOD) activity in the skin homogenate of the wound was measured using the corresponding kits. The expressions of Nrf-2, HO-1, NQO-1, VEGF, and PDGF were measured using the real-time fluorescence quantitative method. We observed that HRW wounds showed an increased rate of wound healing, and a faster average healing time compared with DW. Histopathology showed that in the HRW group, the average thickness of the epidermis was significantly lower than the DW group. The average number of blood vessels in the HRW group was higher than the DW group. The MDA levels were higher in the DW group than in the HRW group, but the SOD levels were higher in the HRW group than in the DW group. The results of qRT-PCR showed that the expression of each gene was significantly different between the two groups. HRW treatment promoted skin wound healing in dogs, accelerated wound epithelization, reduced inflammatory reaction, stimulated the expression of cytokines related to wound healing, and shortened wound healing time.
RESUMO
BACKGROUND: Captive amphibians frequently receive antibiotic baths to control bacterial diseases. The potential collateral effect of these antibiotics on the microbiota of frogs is largely unknown. To date, studies have mainly relied on oral administration to examine the effects of antibiotics on the gut microbiota; in contrast, little is known regarding the effects of bath-applied antibiotics on the gut microbiota. The gut microbiota compositions of the gentamicin, recovery, and control groups were compared by Illumina high-throughput sequencing, and the functional profiles were analysed using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). Furthermore, the relationship between the structure and predicted functional composition of the gut microbiota was determined. RESULTS: The alpha diversity indices were significantly reduced by the gentamicin bath, illustrating that this treatment significantly changed the composition of the gut microbiota. After 7 days, the gut microbiota of the recovery group was not significantly different from that of the gentamicin group. Forty-four indicator taxa were selected at the genus level, comprising 42 indicators representing the control group and 2 indicators representing the gentamicin and recovery groups. Potential pathogenic bacteria of the genera Aeromonas, Citrobacter, and Chryseobacterium were significantly depleted after the gentamicin bath. There was no significant positive association between the community composition and functional composition of the gut microbiota in the gentamicin or control frogs, indicating that the functional redundancy of the gut bacterial community was high. CONCLUSIONS: Gentamicin significantly changed the structure of the gut microbiota of R. dybowskii, and the gut microbiota exhibited weak resilience. However, the gentamicin bath did not change the functional composition of the gut microbiota of R. dybowskii, and there was no significant correlation between the structural composition and the functional composition of the gut microbiota.
Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Gentamicinas/administração & dosagem , Gentamicinas/farmacologia , Ranidae/microbiologia , Administração Tópica , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genéticaRESUMO
The gut microbiota plays a key role in host health, and disruptions to gut bacterial homeostasis can cause disease. However, the effect of disease on gut microbiota assembly remains unclear and gut microbiota-based predictions of health status is a promising yet poorly established field. Using Illumina high-throughput sequencing technology, we compared the gut microbiota between healthy (HA and HB) and diarrhoeic (DS) Rana dybowskii groups and analyzed the functional profiles through a phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) analysis. In addition, we estimated the correlation between gut microbiota structures and predicted the functional compositions. The results showed significant differences in the phylogenetic diversity (Pd), Shannon, and observed richness (Sobs) indices between the DS and HB groups, with significant differences observed in the gut microbiota composition between the DS group and the HA and HB groups. Linear discriminant analysis (LDA) effect size (LEfSe) results revealed that Proteobacteria were significantly enriched in the DS group; Bacteroidetes were significantly enriched in the HA and HB groups; and Aeromonas, Citrobacter, Enterococcus, Hafnia-Obesumbacterium, Morganella, Lactococcus, Providencia, Vagococcus, and Staphylococcus were significantly enriched in the DS group. Venn diagrams revealed that there were many more unique genera in the DS group than the HA and HB groups. Among 102 sensitive species selected using the indicator method, 33 indicated a healthy status and 69 (e.g., Acinetobacter, Aeromonas, Legionella, Morganella, Proteus, Providencia, Staphylococcus, and Vagococcus) indicated a diseased status. There was a significant and positive association between the composition and functional composition of the gut microbiota, thus indicating low functional redundancy of the frog gut bacterial community. Rana dybowskii disease was associated with changes in the gut microbiota, which subsequently disrupted bacterial-mediated functions. The results of this study can aid in revealing the effect of the R. dybowskii gut microbiota on host health and provide a basis for elucidating the mechanism of the occurrence of R. dybowskii disease.
RESUMO
Bovine laminitis causes substantial economic losses and animal welfare problems in dairy farms worldwide. Previously published studies have reported that the inflammatory response plays a central role in the pathogenesis of the disease. To our knowledge, inflammation associated with bovine laminitis induced by high levels of exposure to oligofructose (OF) has not been reported and characterized. In fact, the disease manifestations in this model closely approximate those of clinical laminitis. The objective of this study was to characterize the inflammatory response in OF-induced bovine laminitis. A total of 12 Chinese Holstein dairy heifers were utilized in this study. The heifers were randomly divided into two groups, treatment (n = 6) and control (n = 6). The treatment group heifers were administered OF solutions via a stomach tube (dose: 17 g/kg of body weight). Upon development of a lameness score of 2 with consecutive positive reactions in the same claw, they would be humanely euthanized. Control heifers were administered deionized water (dose: 2 L/100 kg of body weight) and humanely euthanized at 72 h. Real-time quantitative PCR (qPCR) assays were performed to determine the messenger RNA (mRNA) concentrations of inflammatory mediators in the lamellae. Concentrations of interleukin (IL)-1ß, IL-6, IL-8, C-X-C motif chemokine ligand-1 (CXCL-1), macrophage cationic peptide-2 (MCP-2), E-selectin, intercellular adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase-1 (iNOS-1), and plasminogen activator inhibitor-1 (PAI-1) were significantly increased (P < 0.05) in the treatment group. No significant difference was found for tumor necrosis factor alpha (TNF-α), IL-10, CXCL-6, and MCP-1. These results demonstrated and characterized the laminar inflammatory response leading to the pathogenesis of bovine laminitis at the early stages.
RESUMO
Bovine laminitis leads to huge economic losses and animal welfare problems in the dairy industry worldwide. Numerous studies suggested that several metalloproteinases (MPs) may play vital roles in the failure of epidermal attachment. To the best of our knowledge, the present study is the first to investigate and characterize the gene-level changes in distinct MPs and endogenous inhibitors using oligofructose (OF)-induced bovine laminitis model. The objective of this study was to determine aberrant MPs and related inhibitors of bovine laminitis in gene level, and to provide reasonable directions for the further protein-level research. Twelve normal Chinese Holstein dairy heifers were randomly divided into treatment group (n = 6) and control group (n = 6). The heifers in the treatment group were administered with OF solutions at a dose of 17 g/kg of body weight via a stomach tube. The heifers were then humanely euthanized when they met the criteria of bovine laminitis. The heifers in the control group were administered with deionized water at a dose of 2 L/100 kg of body weight. They humanely euthanized at 72 h. The gene expressions of MPs and endogenous inhibitors, namely, matrix metalloproteinases (MMPs), A disintegrin and metalloproteinases (ADAMs), and A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTs), and tissue inhibitors of metalloproteinases (TIMPs) in the lamellae from two groups were determined via real-time quantitative PCR. The gene expressions of MMP-2, MMP-9, ADAMTS-4, and ADAMTS-5 significantly increased (P < 0.05), whereas that of TIMP-2 significantly decreased (P < 0.05) in the treatment group relative to the control group. No significant difference was found in the gene expressions of ADAM-10, ADAM-17, TIMP-1, and TIMP-3. These results indicated that the gene-level imbalanced condition of MPs and their TIMPs may be the basic cause for the failure of epidermal attachment. At the same time, more detailed protein-level studies would be needed to further clarify the roles of MPs and TIMPs in the pathogenesis of bovine laminitis, especially to MMP-2, MMP-9, ADAMTS-4, ADAMTS-5, TIMP-2 as well as related substrates (e.g., aggrecan and versican).
RESUMO
The aim of the present study was to evaluate the role of polygalasaponin F on ischemic myocardial injury in neonatal rats with hypoxic-ischemic brain damage. A primary in-vitro myocardial cell oxygen-glucose deprivation/reperfusion model and an in-vivo middle cerebral artery occlusion model were established. The results demonstrated that polygalasaponin F protects myocardium in hypoxic-ischemic brain injury. The mechanisms of its protective effect involved in (1) reducing oxidant stress injury, (2) reducing the apoptosis rate of myocardial cells through increasing the Bcl-2 protein level and decreasing the Cyt-C and Bax values, and (3) alleviating liver and kidney damage caused by cerebral hypoxia and ischemia via reducing the damage markers. The results of the present study may contribute toward the development of novel strategies for clinical cardioprotection with hypoxic-ischemic brain damage.
Assuntos
Apoptose/efeitos dos fármacos , Hipóxia-Isquemia Encefálica/complicações , Isquemia Miocárdica/etiologia , Estresse Oxidativo/efeitos dos fármacos , Saponinas/farmacologia , Triterpenos/farmacologia , Animais , Animais Recém-Nascidos , Masculino , Substâncias Protetoras/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
The gut microbiota of amphibians is affected by exogenous and endogenous factors. We performed a comprehensive analysis using high-throughput sequencing technology and functional predictions and observed general changes in the gut microbiota of frogs in different growth stages, seasons, and growth environments. There were no significant differences in microbial richness and diversity between juvenile and adult wild frogs, between the summer and autumn groups of captive frogs, or between wild and captive frogs. There were significant differences in the gut microbiota community structure of Rana dybowskii between the summer and autumn groups of captive frogs and between wild and captive R. dybowskii, whereas the differences between juvenile and adult wild frogs were not significant. The dominant gut bacterial phyla in frogs from both captive and wild environments included Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Linear discriminant effect size (LEfSe) analysis showed that Bacteroidetes and Firmicutes were significantly enriched in captive and wild R. dybowskii, respectively linear discriminant analysis (LDA > 4). The core operational taxonomical units (OTUs) that were found in >90% of all frogs tested encompassed 15 core OTUs. The captive frogs exhibited 15 core OTUs in addition to the above overall core microbiota, whereas the wild frogs exhibited 19 core OTUs in addition to the above overall core microbiota. Predictions made using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) suggested that eleven KEGG pathways, such as infectious diseases, immune system diseases, metabolism, metabolism of other amino acids, metabolism of cofactors and vitamins, metabolism of terpenoids and polyketides, neurodegenerative diseases, and transport and catabolism, were enriched in captive frogs. The relative abundance of several red-leg-syndrome-related pathogens increased significantly in captive frogs compared with that in wild frogs. To our knowledge, this is the first study on the effects of individual seasons and captivity on the gut microbiota of frogs.
RESUMO
Partial (2/3) nephrectomy can be performed via the laparoscopic, retroperitoneal, and transperitoneal approach. Outcomes of the three approaches were compared in this study. 2/3 nephrectomy were performed in 21 healthy Bama miniature pigs (mean bodyweight 20.59±2.78kg). Pigs were divided into three groups: those that underwent 2/3 nephrectomy via laparoscopy (LN group, n=7), the retroperitoneal approach (RN group, n=7), or the transperitoneal approach (TN group, n=7). We monitored pre- and postoperative physiologic parameters, blood cell count, and stress and renal function biomarkers. Differences among groups were analyzed. 2/3 nephrectomy was successfully performed in all pigs without any complications. Mean surgical time in the LN group (60.71±7.34min) and the TN group (58.57±4.72min) was significantly longer than that in the RN group (41.14±5.33min). Warm ischemia in the LN group (38±7.57min) was significantly longer than that in the TN group (28.86±4.53min), which was significantly longer than that in the RN group (17.86±2.34min). The postoperative serum concentration of C-reactive protein in the TN group was significantly higher than that in the LN group (p<0.05). So retroperitoneal approach was best choice in case of bilateral renal lesion resulted in shortest ischemia time, and laparoscopic partial nephrectomy should be the primary choice in majority situations resulted in less body stress, smaller surgical incisions and less blood loss.
Assuntos
Laparoscopia/veterinária , Nefrectomia/veterinária , Duração da Cirurgia , Suínos/cirurgia , Animais , Proteína C-Reativa , Feminino , Rim/patologia , Laparoscopia/métodos , Masculino , Nefrectomia/métodos , Período Pós-Operatório , Espaço Retroperitoneal , Resultado do TratamentoRESUMO
It has been demonstrated that video-assisted thoracoscopic surgery (VATS) is feasible and safe in humans and animal models. The aim of the present study was to compare the surgical outcome using VATS with that of the standard transthoracic approach for pneumonectomy in dogs, to determine the acute-phase reaction in VATS pneumonectomy, and to analyze the difference between VATS and the standard transthoracic approach. A total of 14 dogs were divided into two groups (n=7); one group underwent VATS and the other group underwent a transthoracic pneumonectomy. Pre-, intra- and post-operative physiologic parameters were monitored, in addition to the blood cell count and serum acute-phase protein (APP) concentrations. The APP and hemodynamic changes between the two approaches were analyzed. Mean surgical time in the VATS group (176.7 min) was significantly longer compared with the open group (132.4 min). All APP concentrations were significantly increased at day 1 postoperation and gradually decreased to preoperative concentrations. The serum concentration of C-reactive protein on day 3 and the white blood cell count on day 1 were significantly higher following surgery in the open group compared with the VATS group (P<0.05). No differences were observed in the physiological parameters between the two groups. Although VATS took longer, animals experienced smaller incision and less stress. Therefore, the VATS approach was satisfactory for total pneumonectomy.
RESUMO
We review recent progress in the development of two-dimensional (2-D) photonic crystal (PC) materials for chemical and biological sensing applications. Self-assembly methods were developed in our laboratory to fabricate 2-D particle array monolayers on mercury and water surfaces. These hexagonal arrays strongly forward Bragg diffract light to report on their array spacings. By embedding these 2-D arrays onto responsive hydrogel surfaces, 2-D PC sensing materials can be fabricated. The 2-D PC sensors utilize responsive polymer hydrogels that are chemically functionalized to show volume phase transitions in selective response to particular chemical species. Novel hydrogels were also developed in our laboratory by cross-linking proteins while preserving their native structures to maintain their selective binding affinities. The volume phase transitions swell or shrink the hydrogels, which alter their 2-D array spacings, and shift their diffraction wavelengths. These shifts can be visually detected or spectrally measured. These 2-D PC sensing materials have been used for the detection of many analytes, such as pH, surfactants, metal ions, proteins, anionic drugs, and ammonia. We are exploring the use of organogels that use low vapor pressure ionic liquids as their mobile phases for sensing atmospheric analytes.
Assuntos
Técnicas Biossensoriais/métodos , Técnicas de Química Analítica/instrumentação , Nanoestruturas , Fótons , Técnicas Biossensoriais/instrumentação , HumanosRESUMO
We fabricated a two-dimensional (2-D) photonic crystal lectin sensing material that utilizes light diffraction from a 2-D colloidal array attached to the surface of a hydrogel that contains mannose carbohydrate groups. Lectin-carbohydrate interactions create hydrogel cross-links that shrink the hydrogel volume and decrease the 2-D particle spacing. This mannose containing 2-D photonic crystal sensor detects Concanavalin A (Con A) through shifts in the 2-D diffraction wavelength. Con A concentrations can be determined by measuring the diffracted wavelength or visually determined from the change in the sensor diffraction color. The concentrations are easily monitored by measuring the 2-D array Debye ring diameter. Our observed detection limit for Con A is 0.02 mg/mL (0.7 µM). The 2-D photonic crystal sensors are completely reversible and can monitor Con A solution concentration changes.
Assuntos
Concanavalina A/análise , Análise Serial de Proteínas , Resinas Acrílicas/química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Manose/química , Fótons , Raios UltravioletaRESUMO
Gastric cancer (GC) is one of the leading causes of cancer death in the world. The role of histone deacetylase 4 (HDAC4) in specific cell and tissue types has been identified. However, its biological roles in the development of gastric cancer remain largely unexplored. Quantitative real time PCR (qRT-PCR) and western blot were used to analyze the expression of HDAC4 in the clinical samples. siRNA and overexpression of HDAC4 and siRNA p21 were used to study functional effects in a proliferation, a colony formation, a adenosine 5'-triphosphate (ATP) assay and reactive oxygen species(ROS) generation, cell cycle, cell apoptosis rates, and autophagy assays. HDAC4 was up-regulated in gastric cancer tissues and several gastric cancer cell lines. The proliferation, colony formation ability and ATP level were enhanced in HDAC4 overexpression SGC-7901 cells, but inhibited in HDAC4 knockdown SGC-7901 cells. HDAC4 knockdown led to G0/G1 phase cell arrest and caused apoptosis and ROS increase. Moreover, HDAC4 was found to inhibit p21 expression in gastric cancer SGC-7901 cells. p21 knockdown dramatically attenuated cell proliferation inhibition, cell cycle arrest, cell apoptosis promotion and autophagy up-regulation in HDAC4-siRNA SGC-7901 cells. We demonstrated that HDAC4 promotes gastric cancer cell progression mediated through the repression of p21. Our results provide an experimental basis for understanding the pro-tumor mechanism of HDAC4 as treatment for gastric cancer.
Assuntos
Inibidor de Quinase Dependente de Ciclina p21/genética , Regulação Neoplásica da Expressão Gênica , Histona Desacetilases/metabolismo , Proteínas Repressoras/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Trifosfato de Adenosina/metabolismo , Idoso , Apoptose/genética , Estudos de Casos e Controles , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células , Histona Desacetilases/genética , Humanos , Pessoa de Meia-Idade , Espécies Reativas de Oxigênio/metabolismo , Proteínas Repressoras/genética , Neoplasias Gástricas/patologia , Ensaio Tumoral de Célula-TroncoRESUMO
A purely laparoscopic four-port approach was created for left hepatectomy in pigs. A polyethylene loop was placed on the left two hepatic lobes for traction and lift. Next, penetrating ligation of the lobes using of a double row of silk sutures was performed to control bleeding. A direct hepatic transection was completed using a monopolar hook electrode without meticulous dissection of the left hepatic vein. The raw surface of the liver was coagulated and sealed with fibrin glue. Lobes were retrieved through an enlarged portal. Laparoscopic hepatic lobectomy was completed in all pigs without the use of specialized instruments and with a mean operative time of 179 ± 9 min. No significant perioperative complications were observed. The average weight of each resected lobe was 180 ± 51 g. Complete blood count as well as serum organics and enzyme levels normalized after about 2 weeks. During necropsy, adhesion of the hepatic raw surface to the gastric wall and omentum were observed. No other abnormalities were identified. This minimally invasive left hepatectomy technique in swine could serve as a useful model for investigating liver diseases and regeneration, and offer preclinical information to improve hepatobiliary surgical procedures.
Assuntos
Hepatectomia/veterinária , Suínos/cirurgia , Animais , Feminino , Hepatectomia/métodos , Laparoscopia/métodos , Laparoscopia/veterinária , Fígado/cirurgia , Masculino , Cuidados Pós-Operatórios/métodos , Cuidados Pós-Operatórios/veterinária , Porco Miniatura/cirurgiaRESUMO
Bovine and human serum albumin (BSA and HSA) are globular proteins that function as bloodstream carriers of hydrophobes such as fatty acids and drugs. We fabricated novel photonic crystal protein hydrogels by attaching 2D colloidal arrays onto pure BSA and HSA hydrogels. The wavelengths of the diffracted light sensitively report on the protein hydrogel surface area. The binding of charged species to the protein hydrogel gives rise to Donnan potentials that change the hydrogel volume causing shifts in the diffraction. These photonic crystal protein hydrogels act as sensitive Coulometers that monitor the hydrogel charge state. We find multiple high-affinity BSA and HSA binding sites for salicylate, ibuprofen and picosulfate by using these sensors to monitor binding of charged drugs. We demonstrate proof-of-concept for utilizing protein hydrogel sensors to monitor protein-ionic species binding.
Assuntos
Hidrogéis/química , Proteínas/química , Albumina Sérica/química , Animais , Bovinos , Ácidos Graxos/química , Humanos , Concentração de Íons de Hidrogênio , Ligantes , Ligação Proteica , Soroalbumina Bovina/químicaRESUMO
We report the fabrication of large area, thin asymmetric free-standing two-dimensional (2-D) photonic crystals. We fabricate large area 2-D close-packed monodisperse polystyrene (PS) particle monolayers at air/water interfaces by using our needle tip flow method. We then layer tetraethyl orthosilicate (TEOS) onto the 2-D array to form a thin TEOS layer on the 2-D particle array on water. The hemispheres of PS particles located within the TEOS phase swell such that the adjacent particle hemispheres fuse. After TEOS evaporation, we obtain a free-standing connected photonic crystal film of hemispheres that efficiently diffracts light. The other side of the photonic crystal film consists of a fused connecting thin, flat sheet. Reactive ion etching (RIE) of the asymmetric films forms unusual, rough particle 2-D arrays and 2-D flower-like arrays. Mechanical abrasion allows one to separate the resulting novel Janus particles.
RESUMO
We attach 2-D colloidal arrays onto the surface of hydrogels containing biotin. The hydrogel volume shrinks with increasing concentrations of avidin due to the formation of avidin-biotin crosslinks. This causes the Debye diffraction ring diameter to increase, and the 2-D diffraction wavelength to blue-shift.