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Fluids under extreme confinement show characteristics significantly different from those of their bulk counterpart. This work focuses on water confined within the complex cavities of highly hydrophobic metal-organic frameworks (MOFs) at high pressures. A combination of high-pressure intrusion-extrusion experiments with molecular dynamic simulations and synchrotron data reveals that supercritical transition for MOF-confined water takes place at a much lower temperature than in bulk water, â¼250 K below the reference values. This large shifting of the critical temperature (Tc) is attributed to the very large density of confined water vapor in the peculiar geometry and chemistry of the cavities of Cu2tebpz (tebpz = 3,3',5,5'-tetraethyl-4,4'-bipyrazolate) hydrophobic MOF. This is the first time the shift of Tc is investigated for water confined within highly hydrophobic nanoporous materials, which explains why such a large reduction of the critical temperature was never reported before, neither experimentally nor computationally.
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Liquid porosimetry experiments reveal a peculiar trend of the intrusion pressure of water in hydrophobic Cu2(3,3',5,5'-tetraethyl-4,4'-bipyrazolate) MOF. At lower temperature (T) range, the intrusion pressure (Pi) increases with T. For higher T values, Piâ first reaches a maximum and then decreases. This is at odds with the Young-Laplace law, which for systems showing a continuous decrease of contact angle with T predicts a corresponding reduction of the intrusion pressure. Though the Young-Laplace law is not expected to provide quantitative predictions at the subnanoscale of Cu2(tebpz) pores, the physical intuition suggests that to a reduction of their hydrophobicity corresponds a reduction of the Pi. Molecular dynamics simulations and sychrothron experiments allowed to clarify the mechanism of the peculiar trend of Pi with T. At increasing temperatures the vapor density within the MOF' pores grows significantly, bringing the corresponding partial pressure to ≈5 MPa. This pressure, which is consistent with the shift of Pi observed in liquid porosimetry, represents a threshold to be overcame before intrusion takes place. Beyond some value of temperature, the phenomenon of reduction of hydrophobicity (and water surface tension) dominated over the opposite effect of increase of vapor pressure and Pi inverts its trend with T.
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BACKGROUND: Gastrointestinal motility disorders tend to develop after pancreaticoduodenectomy (PD). The objectives of this study were: (1) to investigate the impact of needleless transcutaneous neuromodulation (TN) on the postoperative recuperation following pancreaticoduodenectomy (PD), and (2) to explore the underlying mechanisms by which TN facilitates the recovery of gastrointestinal function after PD. METHODS: A total of 41 patients scheduled for PD were randomized into two groups: the TN group (n = 21) and the Sham-TN group (n = 20). TN was performed at acupoints ST-36 and PC-6 twice daily for 1 h from the postoperative day 1 (POD1) to day 7. Sham-TN was performed at non-acupoints. Subsequent assessments incorporated both heart rate variation and dynamic electrogastrography to quantify alterations in vagal activity (HF) and gastric pacing activity. RESULTS: 1)TN significantly decreased the duration of the first passage of flatus (p < 0.001) and defecation (p < 0.01) as well as the time required to resume diet (p < 0.001) when compared to sham-TN;2)Compared with sham-TN, TN increased the proportion of regular gastric pacing activity (p < 0.01);3) From POD1 to POD7, there was a discernible augmentation in HF induced by TN stimulation(p < 0.01);4) TN significantly decreased serum IL-6 levels from POD1 to POD7 (p < 0.001);5) TN was an independent predictor of shortened hospital stay(ß = - 0.349, p = 0.035). CONCLUSION: Needleless TN accelerates the recovery of gastrointestinal function and reduces the risk of delayed gastric emptying in patients after PD by enhancing vagal activity and controlling the inflammatory response.
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Pancreaticoduodenectomía , Estómago , Humanos , Pancreaticoduodenectomía/efectos adversos , Tiempo de Internación , Vaciamiento Gástrico , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiologíaRESUMEN
H2A.Z, one of the most well-known variants of histone H2A, has been extensively investigated on its dual roles in gene transcription in recent years. In this review, we focus on the intricate involvement of H2A.Z in transcriptional regulation, including the assembly of distinct H2A.Z subtypes, post-translational modifications and genomic distributions. Emphasis is placed on the biological and pathophysiological implications, particularly in tumorigenesis and nervous system development. We summarize the dynamic regulatory mechanisms governing H2A.Z deposition or eviction on chromatin to provide insights for understanding the diversity of histone variants and promoting the search of new targets in concerned disease diagnosis and treatment.
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Histonas , Nucleosomas , Histonas/metabolismo , Cromatina , Regulación de la Expresión Génica , GenomaRESUMEN
This study induced biological stress in Sorbus pohuashanensis suspension cell(SPSC) with yeast extract(YE) as a bio-tic elicitor and isolated and identified secondary metabolites of triterpenoids produced under stress conditions. Twenty-six triterpenoids, including fifteen ursane-type triterpenoids(1-15), two 18,19-seco-ursane-type triterpenoids(16-17), four lupine-type triterpenoids(18-21), two cycloartane-type triterpenoids(22-23), and three squalene-type triterpenoids(24-26), were isolated and purified from the methanol extract of SPSC by chromatography on silica gel, MCI, Sephadex LH-20, and MPLC. Their structures were elucidated by spectroscopic analyses. All triterpenoids were isolated from SPSC for the first time and 22-O-acetyltripterygic acid A(1) was identified as a new compound. Selected compounds were evaluated for antifungal, antitumor, and anti-inflammatory activities, and compound 1 showed an inhibitory effect on NO production in LPS-induced RAW264.7 cells.
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Triterpenos Pentacíclicos , Sorbus , Triterpenos , Animales , Ratones , Sorbus/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/metabolismo , Células RAW 264.7 , Estructura MolecularRESUMEN
Intestinal fibrosis is a common complication of inflammatory bowel disease. There is still a lack of effective drugs for the prevention or treatment of intestinal fibrosis. Heat shock protein 47 (HSP47) plays a key role in the development of intestinal fibrosis. In this study we investigated the therapeutic potential and underlying mechanisms of fraxinellone, a degraded limonoid isolated from the root bark of Dictamnus dasycarpus, in the treatment of intestinal fibrosis. Intestinal fibrosis was induced in mice by dextran sodium sulfate (DSS) treatment. DDS-treated mice were administered fraxinellone (7.5, 15, 30 mg·kg-1·d-1, i.g.) for 45 days. We showed that fraxinellone administration dose-dependently alleviated DSS-induced intestinal impairments, and reduced the production of intestinal fibrosis biomarkers such as α-smooth muscle actin (SMA), collagen I, hydroxyproline, fibronectin and laminin, and cytokines such as TGF-ß, TNF-α and IL-ß. We then established in vitro intestinal fibrosis cell models in SW480 and HT-29 cells, and demonstrated that treatment with fraxinellone (3, 10, 30 µM) significantly relieved TGF-ß-induced fibrosis responses by inhibiting the TGF-ß/Smad2/3 signaling pathway. Molecular docking suggested that the fraxinellone might disrupt the interaction between HSP47 and collagen, which was confirmed by coimmunoprecipitation experiments. SPR analysis showed that fraxinellone had a high affinity for HSP47 with a Kd value of 3.542 × 10-5 M. This study provides a new example of HSP47-collagen intervention by a natural compound and has important implications for the clinical treatment of inflammation-induced issue fibrosis.
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Colágeno , Proteínas del Choque Térmico HSP47 , Ratones , Animales , Proteínas del Choque Térmico HSP47/metabolismo , Simulación del Acoplamiento Molecular , Colágeno/metabolismo , Fibrosis , Epitelio/metabolismo , Factor de Crecimiento Transformador betaRESUMEN
PURPOSE: Older individuals are priority coronavirus disease 2019 (COVID-19) vaccine recipients. Our aim was to investigate the prevalence of and factors influencing vaccine hesitancy in older individuals living in nursing homes and communities. METHODS: A self-administered COVID-19 vaccine hesitancy survey was conducted from September 2021 to December 2021 among people aged ≥ 60 years in eight nursing homes (382 participants) and the community (112 participants) in Taizhou, China. The response rate was 72.1% (382/530) for older adults in nursing homes and 68.7% (112/163) for older adults in the community. RESULTS: We found that 58.1% of the older individuals in nursing homes and 36.6% of those in the community were hesitant to receive the COVID-19 vaccine and that there was a statistically significant difference (P < 0.001). Multiple logistic regression results indicated that the main factors influencing hesitation among the older individuals in nursing homes were being male (Odds Ratio (OR) = 1.67, 95% Confidence Interval (CI): 1.01-2.76); their cognitive level, including having a high perceived risk of COVID-19 infection (OR = 3.06, 95% CI: 1.73-5.43) or the perception of low vaccine safety (OR = 3.08, 95% CI: 1.545- 6.145); anxiety (OR = 3.43, 95% CI: 1.96-5.99); and no previous influenza vaccination (OR = 1.82, 95% CI: 1.13-2.93); whereas those for older individuals in the community were comorbid chronic diseases (OR = 3.13, 95% CI: 1.11- 8.78) and community workers not recommending the vaccine (OR = 8.223, 95% CI: 1.77-38.27). CONCLUSION: The proportion of older individuals in nursing homes who were hesitant to receive the COVID-19 vaccine was significantly higher than for older individuals in the community. Targeted measures should be implemented to reduce vaccine hesitancy and improve vaccination rates in response to the special environment of nursing homes and the characteristics of this population.
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COVID-19 , Humanos , Masculino , Anciano , Femenino , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19/uso terapéutico , Vacunación , China/epidemiología , Casas de SaludRESUMEN
Tin disulfide (SnS2 ) is a promising candidate for electrosynthesis of CO2 -to-formate while the low activity and selectivity remain a great challenge. Herein, we report the potentiostatic and pulsed potential CO2 RR performance of SnS2 nanosheets (NSs) with tunable S-vacancy and exposure of Sn-atoms or S-atoms prepared controllably by calcination of SnS2 at different temperatures under the H2 /Ar atmosphere. The catalytic activity of S-vacancy SnS2 (Vs -SnS2 ) is improved 1.8â times, but it exhibits an exclusive hydrogen evolution with about 100 % FE under all potentials investigated in the static conditions. The theoretical calculations reveal that the adsorption of *H on the Vs -SnS2 surface is energetically more favorable than the carbonaceous intermediates, resulting in active site coverage that hinders the carbon intermediates from being adsorbed. Fortunately, the main product can be switched from hydrogen to formate by applying pulsed potential electrolysis benefiting from in situ formed partially oxidized SnS2-x with the oxide phase selective to formate and the S-vacancy to hydrogen. This work highlights not only the Vs -SnS2 NSs lead to exclusively H2 formation, but also provides insights into the systematic design of highly selective CO2 reduction catalysts reconstructed by pulsed potential electrolysis.
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Shape complementarity is a biological craft for precisely binding substrates at protein-protein interfaces. An analogy to such a function can be drawn conceptually for crystalline porous solids; yet the manifested entities are rare in reticular chemistry. The bottleneck-shaped pores carved out of a metal-organic framework, Zn(MIBA)2 (aka. MAF-stu-13), can perfectly accommodate benzene molecules. Remarkably, its framework adapts to the optimal guest binding-the enhanced host-guest interactions in the neck in turn minimize the guest-guest repulsion in the pore to the extent it turns into attraction-as demonstrated by the combined X-ray structural and DFT computational studies. This adaptive material can be used for liquid-phase production of ultrahigh-purity (≥99 %) cyclohexane, achieving a balance between uptake capacity and separation selectivity and surpassing the performances of other porous and nonporous crystals reported recently (e.g. product purity 99.4 % vs. 97.5 % to date).
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Ciclohexanos/aislamiento & purificación , Imidazoles/química , Estructuras Metalorgánicas/química , Ciclohexanos/química , Modelos Moleculares , Tamaño de la PartículaRESUMEN
Over the past decades, organometallic complexes with precious elements, such as ruthenium and iridium, are widely used as visible-light photoredox catalysts. Recently, more and more complexes based on earth-abundant and inexpensive elements have been used as sensitizers in photochemistry. Although the photoexcited state lifetimes of iron complexes are typically shorter than those of traditional photosensitizers, the utilization of iron catalysts in photochemistry has sprung up owing to their abundance, low price, nontoxicity, and novel properties, including exhibiting ligand to metal charge transfer states. This concept focuses on recent advances in light-driven iron catalysis in organic transformations, including iron/photoredox dual catalysis, light-induced iron photoredox catalysis and light-induced generation of active iron catalysts. The prospect for the future of this field is also discussed.
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BACKGROUND: Hepatocellular carcinoma (HCC) is one of the main causes of cancer-related death. This study aims to explore the role and underlying mechanism of H19 in HCC. METHODS: qRT-PCR detected miR-15b-5p and H19 expression, as well as the mRNA level of EMT-associated genes. Western blotting detected protein level of EMT-associated genes. Immunohistochemistry (IHC) examined CDC42 in HCC tissues. Dual luciferase reporter assay verified the regulatory mechanism among H19, miR-15b and CDC42. Colony formation, wound healing assay, transwell, flow cytometry measured proliferation, migration, invasion and apoptosis, respectively. RESULTS: H19 and CDC42 were up-regulated while miR-15b was down-regulated in HCC cells and tissues. miR-15b interacted with H19 and CDC42 3'-UTR. H19 knockdown inhibited proliferation, migration and invasion, and increased apoptosis, which was rescued by miR-15b inhibitor. H19 knockdown suppressed CDC42/PAK1 pathway and EMT progress. CONCLUSION: H19 knockdown inhibited proliferation, migration and invasion, and promoted apoptosis of HCC cells via targeting miR-15b/CDC42/PAK1 axis.
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Carcinoma Hepatocelular , Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Hepáticas , MicroARNs , Proteínas de Neoplasias , ARN Largo no Codificante , ARN Neoplásico , Proteína de Unión al GTP cdc42 , Quinasas p21 Activadas , Adulto , Anciano , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Femenino , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Masculino , MicroARNs/genética , MicroARNs/metabolismo , Persona de Mediana Edad , Invasividad Neoplásica , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , Proteína de Unión al GTP cdc42/genética , Proteína de Unión al GTP cdc42/metabolismo , Quinasas p21 Activadas/genética , Quinasas p21 Activadas/metabolismoRESUMEN
BACKGROUND: there is an increasing incidence rate of cholecysto-choledocholithiasis associated with the increasing proportion of senile individuals. METHODS: a total of 100 elderly patients (over 80 years of age) suffering both from cholelithiasis and choledocholithiasis were retrospectively studied from January 2010 to December 2016. Patients were scheduled for either a single-stage or two-stage procedure. The LCBDE group (n = 54) included cases that underwent a single stage procedure of laparoscopic exploration of the common bile duct combined with cholecystectomy. The ERCP/EST group (n = 46) included cases that underwent a two stage procedure of preoperative endoscopic retrograde cholangiopancreaticography with endoscopic sphincterotomy followed by cholecystectomy. Comorbidity conditions, presenting symptoms, bile duct clearance, length of hospital stay and the frequency of procedural, postoperative and long-term complications were recorded. RESULTS: the LCBDE group had a higher stones clearance rate than the ERCP/EST group (100.0% vs 89.1%, p < 0.05). Postoperative complications and hospitalization length were comparable in the two groups (p > 0.05). There were more procedural complications in the ERCP/EST group than in the LCBDE group (10.8% vs 0%, p < 0.05). Furthermore, a patient in the ERCP/EST group died due to duodenal perforation. More patients in the ERCP/EST group experienced long-term complications than those in the LCBDE group (23.9% vs 3.7%, p < 0.05) during a mean follow-up period of 28.4 months. CONCLUSIONS: the single-stage procedure is a safe and effective technique for elderly patients with cholecysto-choledocholithiasis. LCBDE provides a good stone clearance rate with few long term complications.
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Colangiopancreatografia Retrógrada Endoscópica , Colecistectomía Laparoscópica/métodos , Colecistolitiasis/cirugía , Coledocolitiasis/cirugía , Esfinterotomía Endoscópica/métodos , Anciano de 80 o más Años , Colecistectomía/efectos adversos , Colecistectomía/métodos , Colecistectomía Laparoscópica/efectos adversos , Colecistolitiasis/complicaciones , Coledocolitiasis/complicaciones , Conducto Colédoco/cirugía , Femenino , Humanos , Laparoscopía , Tiempo de Internación , Masculino , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Esfinterotomía Endoscópica/efectos adversosRESUMEN
BACKGROUND: Gastric gastrointestinal stromal tumor (GIST), intro-abdominal and retroperitoneal neoplasms are distinct tumors arising from different cell layers; therefore, coexistence of such tumors is relatively rare. CASE PRESENTATION: A man complained of early satiety for 2 mouths, whose upper gastrointestinal (GI) endoscopy showed a tumor arising from the greater curvature of gastric body and extending into the lumen. Abdominal computed tomography (CT) revealed coexistence of gastric, intro-abdominal and retroperitoneal masses. Wedge resection for gastric tumor, resection for intro-abdominal and retroperitoneal tumors were done. The postoperative histological examination suggested simultaneous development of a gastric GIST, intro-abdominal and retroperitoneal myxoid liposarcomas. CONCLUSION: Although both GISTs and liposarcomas originate from mesenchymal tissues, simultaneous development of a gastric GIST, intro-abdominal and retroperitoneal liposarcomas is the first such case to be reported in the literature.
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Neoplasias Gastrointestinales/diagnóstico por imagen , Tumores del Estroma Gastrointestinal/diagnóstico por imagen , Liposarcoma/diagnóstico por imagen , Neoplasias Retroperitoneales/diagnóstico por imagen , Procedimientos Quirúrgicos del Sistema Digestivo , Endoscopía Gastrointestinal , Neoplasias Gastrointestinales/cirugía , Tumores del Estroma Gastrointestinal/cirugía , Humanos , Liposarcoma/cirugía , Masculino , Persona de Mediana Edad , Neoplasias Retroperitoneales/cirugía , Tomografía Computarizada por Rayos XRESUMEN
INTRODUCTION: Gastrointestinal stromal tumors (GISTs) are infrequently reported to cause gastroduodenal intussusception, especially in the cases with complete pylorus obstruction. GISTs comprise only 1â-â3â% of all gastrointestinal tract tumors, and most of them strongly express the c-KIT protein. Approximately 5â% of GISTs show negative staining of c-KIT. CASE PRESENTATION: A 69-year-old man complained of acute abdominal pain accompanied with nausea and vomiting for 6 hours. Emergency endoscopic examination, upper gastroenterography, and computed tomography scan suggested gastroduodenal intussusception and pylorus obstruction induced by a gastric GIST. Laparoscopic exploration and wedge resection of the tumor were performed in the patient. Postoperative histological examination showed a gastric GIST with c-KIT-negative expression. CONCLUSION: Herein, we report the unique findings of a c-KIT-negative gastric GIST presenting with gastroduodenal intussusception and pylorus obstruction. We also reviewed the English language literature of gastroduodenal intussusception induced by GISTs and put our case in the context of the previously reported cases.
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Obstrucción de la Salida Gástrica , Tumores del Estroma Gastrointestinal , Intususcepción , Neoplasias Gástricas , Anciano , Obstrucción de la Salida Gástrica/diagnóstico , Obstrucción de la Salida Gástrica/etiología , Obstrucción de la Salida Gástrica/cirugía , Tumores del Estroma Gastrointestinal/complicaciones , Tumores del Estroma Gastrointestinal/genética , Humanos , Intususcepción/diagnóstico , Intususcepción/etiología , Intususcepción/cirugía , Masculino , Proteínas Proto-Oncogénicas c-kit , Píloro , Neoplasias Gástricas/complicacionesRESUMEN
Background Choledocholithiasis can be managed by transcystic (TC) and transduct (TD) stone extraction or using cholangioscopy through the left hepatic duct orifice (LHD). Objective The aim of this study is to evaluate the safety and effectiveness of common bile duct exploration through the TC approach, TD approach, and LHD approach for choledocholithiasis, with a specific emphasis on the TC and LHD approaches versus the TD approach. Methods Between January 2011 and June 2014, a total of 172 choledocholithiasis patients accompanied by cholecystitis and/or left intrahepatic gallstones were scheduled for laparoscopic or open common bile duct (CBD) exploration using cholangioscopy through the CBD (TD group: nâ=â72), cystic duct (TC group: nâ=â63), or LHD orifice (LHD group: nâ=â37). T-tube insertion was performed in selected patients. Patients were regularly followed up at bimonthly intervals or more frequently in presence of any symptom. Primary outcomes measures included overall operative time, length of hospital stay, and postoperative bile leaks. Results Successful bile duct clearance was 100â% in the TD group, 93.6â% in the TC group, and 90.9â% in the LHD group.âSixteen cases in the TD group had T-tube placement in contrast to no cases in the TC and LHD groups. There were more bile leaks after TD stone extraction (12.5â%) than TC (3.2â%) and LHD stone extraction (0â%), which prolonged hospitalization in the TD group more than in the TC and LHD groups. For choledocholithiasis patients accompanied by cholecystitis, 2 groups (TC and TD groups) were comparable in operative time. However, for choledocholithiasis patients accompanied by left intrahepatic gallstones, the LHD group had a significantly shorter operative time than the TD group (121.1â±â16.9 minutes vs. 149.3â±â42.8 minutes, pâ<â0.05). Conclusion The TD group had a higher stone clearance rate but was associated with a higher risk of bile leaks. TC and LHD stone extraction, which seems to be the more effective approach with lower complication rates, is an accessible technique that simplifies the operation procedure by avoiding choledochotomy and subsequent T-tube insertion.
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Conductos Biliares/cirugía , Coledocolitiasis/cirugía , Coledocostomía/métodos , Conducto Colédoco/cirugía , Drenaje/métodos , Conducto Hepático Común/cirugía , Laparoscopía/métodos , Coledocolitiasis/diagnóstico por imagen , Humanos , Laparoscopía/efectos adversos , Tiempo de InternaciónRESUMEN
Three new polyhydroxylated sterol derivatives topsensterols A-C (1-3) have been isolated from a marine sponge Topsentia sp. collected from the South China Sea. Their structures were elucidated by detailed analysis of the spectroscopic data, especially the NOESY spectra. Topsensterols A-C (l-3) possess novel 2ß,3α,4ß,6α-tetrahydroxy-14α-methyl Δ(9(11)) steroidal nuclei with unusual side chains. Compound 2 exhibited cytotoxicity against human gastric carcinoma cell line SGC-7901 with an IC50 value of 8.0 µM. Compound 3 displayed cytotoxicity against human erythroleukemia cell line K562 with an IC50 value of 6.0 µM.
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Antineoplásicos/farmacología , Leucemia Eritroblástica Aguda/tratamiento farmacológico , Poríferos/química , Esteroles/farmacología , Neoplasias Gástricas/tratamiento farmacológico , Animales , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Antineoplásicos/uso terapéutico , Humanos , Concentración 50 Inhibidora , Células K562 , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Esteroles/química , Esteroles/aislamiento & purificación , Esteroles/uso terapéuticoRESUMEN
A man complained of upper abdominal pain and early satiety for one month. An upper gastrointestinal endoscopy showed nothing specia. A CT scan of the abdomen was perfromed, which demonstrated a huge heterogeneous retroperitoneal mass close to the dorsal wall of the stomach and surrounding the abdominal aortic and celiac trunk. The resected specimen suggested that an un-regular tumor invaded to the dorsal wall of the stomach. Postoperative histological examination confirmed that it was a gastric squamous cell carcinoma.
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Carcinoma de Células Escamosas/diagnóstico por imagen , Neoplasias Retroperitoneales/diagnóstico por imagen , Neoplasias Gástricas/diagnóstico por imagen , Anastomosis Quirúrgica/métodos , Carcinoma de Células Escamosas/cirugía , Unión Esofagogástrica/cirugía , Gastrectomía , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Retroperitoneales/cirugía , Neoplasias Gástricas/cirugía , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: This study was designed to evaluate whether exogenous CRT was beneficial for alleviating MR-induced injury by suppressing ER stress in rat MMECs. METHODS: MMECs were pretreated with CRT (25 pg/mL) for 12 hours, followed by the exposure to 2.856 GHz radiation at a mean power density of 30 mW/cm(2) for six minutes. MR-induced injury in MMECs was evaluated by LDH leakage, apoptosis, and cell viability analysis. The expression of GRP78, CRT, CHOP, Bcl-2, and Bax were examined by Western blot analysis to reflect ER stress response and ER stress-related apoptosis. RESULTS: MR induced marked MMECs injury, as shown by increased LDH leakage and apoptosis rate and decreased cell viability. MR also induced excessive ER stress, characterized by increased expression of GRP78 and CRT, and ER stress-related apoptotic signaling as well, as shown by the upregulation of CHOP and Bax and the downregulation of Bcl-2. Exogenous CRT pretreatment remarkably attenuated MR-induced cell apoptosis and LDH leakage, ER stress, and activation of the ER stress-related apoptotic signaling. CONCLUSIONS: Exogenous CRT attenuates MR-induced ER stress-related apoptosis by suppressing CHOP-mediated apoptotic signaling pathways in MMECs.
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Calbindina 2/metabolismo , Permeabilidad Capilar/efectos de la radiación , Estrés del Retículo Endoplásmico/efectos de la radiación , Células Endoteliales/metabolismo , Microvasos/metabolismo , Microondas/efectos adversos , Animales , Apoptosis/efectos de la radiación , Células Endoteliales/patología , Femenino , Proteínas de Choque Térmico/metabolismo , L-Lactato Deshidrogenasa/metabolismo , Masculino , Microvasos/patología , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de la radiación , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Inflammatory bowel disease (IBD) affects millions of people worldwide. Although the etiology of this disease is uncertain, accumulating evidence indicates a key role for the activated mucosal immune system. In the present study, we examined the effects of the natural compound fraxinellone on dextran sulfate sodium (DSS)-induced colitis in mice, an animal model that mimics IBD. Treatment with fraxinellone significantly reduced weight loss and diarrhea in mice and alleviated the macroscopic and microscopic signs of the disease. In addition, the activities of myeloperoxidase and alkaline phosphatase were markedly suppressed, while the levels of glutathione were increased in colitis tissues following fraxinellone treatment. This compound also decreased the colonic levels of interleukin (IL)-1ß, IL-6, IL-18 and tumor necrosis factor (TNF)-α in a concentration-dependent manner. These effects of fraxinellone in mice with experimental colitis were attributed to its inhibition of CD11b(+) macrophage infiltration. The mRNA levels of macrophage-related molecules in the colon, including intercellular adhesion molecule 1 (ICAM1), vascular cell adhesion molecule 1 (VCAM1), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2), were also markedly inhibited following fraxinellone treatment. The results from in vitro assays showed that fraxinellone significantly reduced lipopolysaccharide (LPS)-induced production of nitric oxide (NO), IL-1ß and IL-18 as well as the activity of iNOS in both THP-1 cells and mouse primary peritoneal macrophages. The mechanisms responsible for these effects were attributed to the inhibitory role of fraxinellone in NF-κB signaling and NLRP3 inflammasome activation. Overall, our results support fraxinellone as a novel drug candidate in the treatment of colonic inflammation.
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Benzofuranos/farmacología , Colitis/metabolismo , Modelos Animales de Enfermedad , Macrófagos Peritoneales/efectos de los fármacos , FN-kappa B/antagonistas & inhibidores , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Animales , Benzofuranos/uso terapéutico , Línea Celular , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Sulfato de Dextran/toxicidad , Relación Dosis-Respuesta a Droga , Humanos , Inflamasomas/antagonistas & inhibidores , Inflamasomas/metabolismo , Macrófagos Peritoneales/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiologíaRESUMEN
Endothelial cells (ECs) are directly exposed to hypoxia and contribute to injury during myocardial ischemia/reperfusion. Hypoxic preconditioning (HPC) protects ECs against hypoxia injury. This study aimed to explore whether HPC attenuates hypoxia/reoxygenation (H/R) injury by suppressing excessive endoplasmic reticulum stress (ERS) in cultured microvascular ECs (MVECs) from rat heart. MVECs injury was measured by lactate dehydrogenase (LDH) leakage, cytoskeleton destruction, and apoptosis. Expression of glucose regulating protein 78 (GRP78) and C/EBP homologous protein (CHOP), activation of caspase-12 (pro-apoptosis factors) and phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) were detected by western blot analysis. HPC attenuated H/R-induced LDH leakage, cytoskeleton destruction, and cell apoptosis, as shown by flow cytometry, Bax/Bcl-2 ratio, caspase-3 activation and terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling. HPC suppressed H/R-induced ERS, as shown by a decrease in expression of GRP78 and CHOP, and caspase-12 activation. HPC enhanced p38 MAPK phosphorylation but decreased that of protein kinase R-like ER kinase (PERK, upstream regulator of CHOP). SB202190 (an inhibitor of p38 MAPK) abolished HPC-induced cytoprotection, downregulation of GRP78 and CHOP, and activation of caspase-12, as well as PERK phosphorylation. HPC may protect MVECs against H/R injury by suppressing CHOP-dependent apoptosis through p38 MAPK mediated downregulation of PERK activation.