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Neurofibromatosis type 1 (NF1) is caused by NF1 gene mutations. Patients with NF1 often have complications with tumors, such as neurofibroma. In order to investigate the pathogenesis of human neurofibroma, a systematic comparison of protein expression levels between Schwann cell-like sNF96.2 cells, which originated from malignant peripheral nerve sheath tumors (MPNST), and normal Schwann cells was performed using 4-D label-free proteomic analysis. In addition, the expression levels and localization of dysregulated proteins were confirmed using a Gene Expression Omnibus (GEO) transcriptomic dataset, Western blot analysis, and immunofluorescence labeling. The effects of SRY-box transcription factor 9 (SOX9) in the neurofibroma and surrounding microenvironment were evaluated in vivo using a tumor transplantation model. The present study observed that SOX9 and procollagen C-endopeptidase enhancer (PCOLCE) were significantly altered. NF1 mutation promoted the nuclear translocation and transcriptional activity of SOX9 in neurofibromas. SOX9 increased collagen VI secretions by enhancing the activation of PCOLCE in neurofibroma cells. These findings might provide new perspectives on the pathophysiological significance of SOX9 in neurofibromas and elucidate a novel molecular mechanism underlying neurofibromas.
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The human intestinal epithelium has an impressive ability to respond to insults and its homeostasis is maintained by well-regulated mechanisms under various pathophysiological conditions. Nonetheless, acute injury and inhibited regeneration of the intestinal epithelium occur commonly in critically ill surgical patients, leading to the translocation of luminal toxic substances and bacteria to the bloodstream. Effective therapies for the preservation of intestinal epithelial integrity and for the prevention of mucosal hemorrhage and gut barrier dysfunction are limited, primarily because of a poor understanding of the mechanisms underlying mucosal disruption. Noncoding RNAs (ncRNAs), which include microRNAs (miRNAs), long ncRNAs (lncRNAs), circular RNAs (circRNAs), and small vault RNAs (vtRNAs), modulate a wide array of biological functions and have been identified as orchestrators of intestinal epithelial homeostasis. Here, we feature the roles of many important ncRNAs in controlling intestinal mucosal growth, barrier function, and repair after injury-particularly in the context of postoperative recovery from bowel surgery. We review recent literature surrounding the relationships between lncRNAs, microRNAs, and RNA-binding proteins and how their interactions impact cell survival, proliferation, migration, and cell-to-cell interactions in the intestinal epithelium. With advancing knowledge of ncRNA biology and growing recognition of the importance of ncRNAs in maintaining the intestinal epithelial integrity, ncRNAs provide novel therapeutic targets for treatments to preserve the gut epithelium in individuals suffering from critical surgical disorders.
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MicroARNs , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , MicroARNs/genética , Mucosa IntestinalRESUMEN
Circular RNAs (circRNAs) are highly expressed in the mammalian intestinal epithelium, but their functions remain largely unknown. Here, we identified the circRNA Cdr1as as a repressor of intestinal epithelial regeneration and defense. Cdr1as levels increased in mouse intestinal mucosa after colitis and septic stress, as well as in human intestinal mucosa from patients with inflammatory bowel disease and sepsis. Ablation of the Cdr1as locus from the mouse genome enhanced renewal of the intestinal mucosa, promoted injury-induced epithelial regeneration, and protected the mucosa against colitis. We found approximately 40 microRNAs, including miR-195, differentially expressed between intestinal mucosa of Cdr1as-knockout (Cdr1as-/-) versus littermate mice. Increasing the levels of Cdr1as inhibited intestinal epithelial repair after wounding in cultured cells and repressed growth of intestinal organoids cultured ex vivo, but this inhibition was abolished by miR-195 silencing. The reduction in miR-195 levels in the Cdr1as-/- intestinal epithelium was the result of reduced stability and processing of the precursor miR-195. These findings indicate that Cdr1as reduces proliferation and repair of the intestinal epithelium at least in part via interaction with miR-195 and highlight a role for induced Cdr1as in the pathogenesis of unhealed wounds and disrupted renewal of the intestinal mucosa.
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Colitis , MicroARNs , Animales , Humanos , Ratones , Proliferación Celular/genética , Colitis/genética , Colitis/patología , Mucosa Intestinal/patología , Mamíferos/genética , MicroARNs/genética , Regeneración/genética , ARN Circular/genéticaRESUMEN
Objective: To investigate the effect of esketamine combined with propofol on patient hemodynamics and its safety in hysteroscopy anesthesia. Methods: A total of 186 hysteroscopic patients admitted to our hospital from January 2021 to January 2022 were selected, and the patients were divided into group K and Group P according to a completely random number table, with 93 cases each. In short, all patients are uniformly numbered and adequately intermixed, according to the prescribed sampling starting point and order, the sample unit numbers were successively drawn from the random number table, until the extraction to the required sample size. Group K was given esketamine combined with propofol intravenously, and group P was given sufentanil combined with propofol intravenously. The changes in respiratory circulation [heart rate (HR), mean arterial pressure (MAP) and oxygen saturation (SpO2)] at the time of entering the operating room (T0), at the beginning of surgery (T1), 10 minutes after surgery(T2), and 10 minutes after the end of surgery (T3) were compared between the two groups, as well as the total time of surgery, the time to wake up after surgery, the amount of propofol used intraoperatively and the proportion of additional propofol were compared. The numerical rating scale (NRS) was used to assess the pain level of patients in both groups at different times after awakening and the occurrence of intraoperative and postoperative adverse reactions such as body movement, respiratory depression, bradycardia, injection site pain, nausea and vomiting, and dizziness were counted in both groups. Results: There were no significant changes in MAP, HR, and SpO2 in Group K at all moments compared with T0 (P > .05), MAP, HR and SpO2 in Group P at T1 and T2 were lower than those at T0 (P < .05). MAP, HR, and SpO2 were significantly lower in Group P at T1 and T2 moments compared with Group K, suggesting that circulatory depression was more pronounced in Group P at T1 and T2 moments (P < .05) and was not conducive to postoperative recovery. Compared with group P, the postoperative recovery time of group K was significantly shorter, and the dosage of propofol and the proportion of additional propofol were significantly lower (P < .05) which was beneficial to the health of patients. The pain level was significantly lower in Group K at 5, 15, and 30 minutes after awakening than in Group P (P < .05). The incidence of adverse reactions such as intraoperative motion, respiratory depression, bradycardia, injection site pain, and dizziness was significantly lower in group K than in group P (P < .05), and there was no significant difference in the incidence of nausea and vomiting between the two groups (P > .05), and prove that esketamine combined with propofol used for anesthesia which have high safety as well as more effective. Conclusion: The use of esketamine compounded with propofol in hysteroscopy anesthesia has less effect on the patient's circulatory and respiratory systems. This protocol can improve the postoperative analgesic effect of anesthesia in patients, reduce the amount of propofol during surgery, have fewer adverse effects and mild symptoms, is safe and effective, and can be used in clinical practice.
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Anestesia , Ketamina , Propofol , Insuficiencia Respiratoria , Femenino , Embarazo , Humanos , Propofol/efectos adversos , Histeroscopía/efectos adversos , Bradicardia , Mareo , Hemodinámica , Dolor , Vómitos , NáuseaRESUMEN
The mammalian intestinal epithelium is a rapidly self-renewing tissue in the body and its homeostasis is tightly controlled by numerous factors at multiple levels. The RNA-binding protein HuR (human antigen R) is intimately involved in many aspects of gut mucosal pathobiology and plays an important role in maintaining integrity of the intestinal epithelium by regulating stability and translation of target mRNAs. Nonetheless, deregulation of HuR expression and altered binding affinity of HuR for target transcripts occur commonly in various gut mucosal disorders. In this review, we highlight the essential role of HuR in the intestinal epithelium homeostasis and discuss recent results that interactions between HuR and noncoding RNAs (ncRNAs), including circular RNAs, long ncRNAs, small vault RNAs, and microRNAs, influence gut mucosal regeneration and regulate barrier function in various pathophysiological conditions. These exciting discoveries advance our knowledge of HuR biological function in the gut mucosa and also create a fundamental basis for developing novel therapies to protect intestinal epithelial integrity in critically ill patients.
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Mucosa Intestinal , ARN Largo no Codificante , Animales , Humanos , Mucosa Intestinal/metabolismo , Epitelio/metabolismo , ARN Largo no Codificante/metabolismo , Homeostasis , Mamíferos/metabolismoRESUMEN
Cardiovascular diseases (CVDs), encompassing ischaemic heart disease, cardiomyopathy, and heart failure, among others, are the most prevalent complications of diabetes and the leading cause of mortality in patients with diabetes. Cell death modalities, including apoptosis, necroptosis, and pyroptosis, have been demonstrated to be involved in the pathogenesis of CVDs. As research progresses, accumulating evidence also suggests the involvement of ferroptosis, a novel form of cell death, in the pathogenesis of CVDs. Ferroptosis, characterised by iron-dependent lipid peroxidation, which culminates in membrane rupture, may present new therapeutic targets for diabetes-related cardiovascular complications. Current treatments for CVDs, such as antihypertensive, anticoagulant, lipid-lowering, and plaque-stabilising drugs, may cause severe side effects with long-term use. Traditional Chinese medicine, with its broad range of activities and minimal side effects, is widely used in China. Numerous studies have shown that active components of Chinese medicine, such as alkaloids, polyphenols, and saponins, can prevent CVDs by regulating ferroptosis. This review summarises the recent findings on the regulatory mechanisms of active components of Chinese medicine against ferroptosis in CVDs, aiming to provide new directions and a scientific basis for targeting ferroptosis for the prevention and treatment of diabetic CVDs.
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A new type of carbon dot (CD)-functionalized solution-gated graphene transistor (SGGT) sensor was designed and fabricated for the highly sensitive and highly selective detection of glutathione (GSH). The CDs were synthesized via a one-step hydrothermal method using DL-thioctic acid and triethylenetetramine (TETA) as sources of S, N, and C. The CDs have abundant amino and carboxyl groups and were used to modify the surface of the gate electrode of SGGT as probes for detecting GSH. Remarkably, the CDs-SGGT sensor exhibited excellent selectivity and ultrahigh sensitivity to GSH, with an ultralow limit of detection (LOD) of up to 10-19 M. To the best of our knowledge, the sensor outperforms previously reported systems. Moreover, the CDs-SGGT sensor shows rapid detection and good stability. More importantly, the detection of GSH in artificial serum samples was successfully demonstrated.
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Grafito , Puntos Cuánticos , Carbono , Límite de Detección , GlutatiónRESUMEN
Gut barrier dysfunction occurs commonly in patients with critical disorders, leading to the translocation of luminal toxic substances and bacteria to the bloodstream. Connexin 43 (Cx43) acts as a gap junction protein and is crucial for intercellular communication and the diffusion of nutrients. The levels of cellular Cx43 are tightly regulated by multiple factors, including polyamines, but the exact mechanism underlying the control of Cx43 expression remains largely unknown. The RNA-binding protein HuR regulates the stability and translation of target mRNAs and is involved in many aspects of intestinal epithelial pathobiology. Here we show that HuR directly bound to Cx43 mRNA via its 3'-untranslated region in intestinal epithelial cells (IECs) and this interaction enhanced Cx43 expression by stabilizing Cx43 mRNA. Depletion of cellular polyamines inhibited the [HuR/Cx43 mRNA] complex and decreased the level of Cx43 protein by destabilizing its mRNA, but these changes were prevented by ectopic overexpression of HuR. Polyamine depletion caused intestinal epithelial barrier dysfunction, which was reversed by ectopic Cx43 overexpression. Moreover, overexpression of checkpoint kinase 2 in polyamine-deficient cells increased the [HuR/Cx43 mRNA] complex, elevated Cx43 levels, and promoted barrier function. These findings indicate that Cx43 mRNA is a novel target of HuR in IECs and that polyamines regulate Cx43 mRNA stability via HuR, thus playing a critical role in the maintenance of intestinal epithelial barrier function.NEW & NOTEWORTHY The current study shows that polyamines stabilize the Cx43 mRNA via HuR, thus enhancing the function of the Cx43-mediated gap junction. These findings suggest that induced Cx43 by HuR plays a critical role in the process by which polyamines regulate intestinal epithelial barrier.
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Conexina 43 , Proteína 1 Similar a ELAV , Poliaminas , ARN Mensajero , Humanos , Conexina 43/genética , Conexina 43/metabolismo , Proteína 1 Similar a ELAV/genética , Proteína 1 Similar a ELAV/metabolismo , Mucosa Intestinal/metabolismo , Poliaminas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Estabilidad del ARNRESUMEN
Rapid self-renewal of the intestinal epithelium requires the activity of intestinal stem cells (ISCs) that are intermingled with Paneth cells (PCs) at the crypt base. PCs provide multiple secreted and surface-bound niche signals and play an important role in the regulation of ISC proliferation. Here, we show that control of PC function by RNA-binding protein HuR via mitochondria affects intestinal mucosal growth by altering ISC activity. Targeted deletion of HuR in mice disrupted PC gene expression profiles, reduced PC-derived niche factors, and impaired ISC function, leading to inhibited renewal of the intestinal epithelium. Human intestinal mucosa from patients with critical surgical disorders exhibited decreased levels of tissue HuR and PC/ISC niche dysfunction, along with disrupted mucosal growth. HuR deletion led to mitochondrial impairment by decreasing the levels of several mitochondrial-associated proteins including prohibitin 1 (PHB1) in the intestinal epithelium, whereas HuR enhanced PHB1 expression by preventing microRNA-195 binding to the Phb1 mRNA. These results indicate that HuR is essential for maintaining the integrity of the PC/ISC niche and highlight a novel role for a defective PC/ISC niche in the pathogenesis of intestinal mucosa atrophy.
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Proteína 1 Similar a ELAV , MicroARNs , Membrana Mucosa , Células de Paneth , Animales , Humanos , Ratones , Transporte Biológico , Fenómenos Fisiológicos Celulares , Mucosa Intestinal , MicroARNs/genética , Proteínas Mitocondriales , Células Madre , Proteína 1 Similar a ELAV/genéticaRESUMEN
AIMS: Cyp2e1 is a crucial CYP450 enzyme participating in diabetes and cardiovascular disorder. However, the role of Cyp2e1 in diabetic cardiomyopathy (DCM) has never been reported. Thus, we intended to identify the effects of Cyp2e1 on cardiomyocytes under high glucose (HG) conditions. METHODS: Identification of differentially expressed genes in DCM and control rats was performed using bioinformatics analysis based on GEO database. The Cyp2e1-knockdown H9c2 and HL-1 cells were established through transfection with si-Cyp2e1. Western blot analysis was performed to determine the expression levels of Cyp2e1, apoptosis-related proteins and PI3K/Akt signaling-associated proteins. TUNEL assay was performed to assess apoptotic rate. Reactive oxygen species (ROS) generation was examined by DCFH2-DA staining assay. RESULTS: From the bioinformatics analysis, Cyp2e1 was confirmed as an upregulated gene in DCM tissues. In vitro assays proved that Cyp2e1 expression was markedly increased in HG-induced H9c2 and HL-1 cells. Cyp2e1 knockdown attenuated HG-induced apoptosis in both H9c2 and HL-1 cells, as proved by deceased apoptotic rate, relative cleaved caspase-3/caspase-3 level, and caspase-3 activity. Cyp2e1 knockdown reduced ROS generation and elevated the expression level of nuclear Nrf2 in HG-induced H9c2 and HL-1 cells. Increased relative levels of p-PI3K/PI3K and p-Akt/Akt were found in Cyp2e1-knockdown H9c2 and HL-1 cells. Inhibition of PI3K/Akt using LY294002 reversed the inhibitory effects of Cyp2e1 knockdown on cell apoptosis and ROS generation on cardiomyocytes. CONCLUSIONS: Cyp2e1 knockdown attenuated HG-induced apoptosis and oxidative stress by activating PI3K/Akt signaling in cardiomyocytes. These findings suggested that Cyp2e1 might be potentially used as an effective therapeutic strategy for DCM.
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Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Animales , Ratas , Apoptosis/genética , Caspasa 3/metabolismo , Citocromo P-450 CYP2E1/metabolismo , Citocromo P-450 CYP2E1/farmacología , Glucosa/farmacología , Glucosa/metabolismo , Miocitos Cardíacos/metabolismo , Estrés Oxidativo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , RatonesRESUMEN
The purpose of this study was to investigate the anti-inflammatory effects of EU-Idd both in vivo and in vitro. In vivo, we used the collagen-induced arthritis (CIA) rat model to investigate the efficacy of EU-Idd on rheumatoid arthritis. Hematoxylin-eosin staining and Safranin O-fast green staining were used to evaluate the pathological status of the ankle joints in CIA rats. Micro-CT scanning was used to investigate bone erosion of the ankle joints. In vitro, the effect of EU-Idd on Th17 cell differentiation was identified by flow cytometry. TRAP staining was used to detect osteoclast cells. HFLS-RA model cells, induced by tumor necrosis factor-α(TNF-α), were used to evaluate the anti-inflammatory effects of EU-Idd while the levels of related inflammatory cytokines and JAK2/STAT3 proteins were detected by RT-qPCR and western blotting. EU-Idd alleviated joint inflammation in CIA rats and exerted protective effects on the ankle joints. EU-Idd also prevented the differentiation of CD4+ T cells into Th17 cells, reduced the number of osteoclasts, and improved the expression levels of bone metabolism-related proteins including OPG and RANKL. Moreover, EU-Idd inhibited the invasion and migration of HFLS-RA cells and downregulated the expression of related inflammatory cytokine genes and the protein expression levels of p-JAK2 and p-STAT3, both in vivo and in vitro. EU-Idd exerts anti-inflammatory and osteoprotective effects by regulating the JAK2/STAT3 pathway in rheumatoid arthritis. These results are beneficial to excavate new pharmaceutical ingredients for rheumatoid arthritis from iridoid.
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Fenton chemistry has been widely studied in a broad range from geochemistry, chemical oxidation to tumor chemodynamic therapy. It was well established that Fe3+/H2O2 resulted in a sluggish initial rate or even inactivity. Herein, we report the homogeneous carbon dot-anchored Fe(III) catalysts (CD-COOFeIII) wherein CD-COOFeIII active center activates H2O2 to produce hydroxyl radicals (â¢OH) reaching 105 times larger than that of the Fe3+/H2O2 system. The key is the â¢OH flux produced from the O-O bond reductive cleavage boosting by the high electron-transfer rate constants of CD defects and its self-regulated proton-transfer behavior probed by operando ATR-FTIR spectroscopy in D2O and kinetic isotope effects, respectively. Organic molecules interact with CD-COOFeIII via hydrogen bonds, promoting the electron-transfer rate constants during the redox reaction of CD defects. The antibiotics removal efficiency in the CD-COOFeIII/H2O2 system is at least 51 times large than the Fe3+/H2O2 system under equivalent conditions. Our findings provide a new pathway for traditional Fenton chemistry.
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The electrochemical upconversion of plastic wastes has been demonstrated as an attractive alternative to the sluggish OER process to simultaneously produce valued chemicals and reduce the energy consumption. Herein, we report a photovoltaic-driven electrocatalytic strategy to upcycle poly(ethylene terephthalate) (PET) into value-added formic acid products and co-produce green hydrogen. The waste PET was dissolved by KOH and then directly pumped into an electrochemical flow reactor (EFR) including CuO nanowires (NWs) anode and Pt/C 20% cathode (PV-EFR) and driven by the commercial silicon photovoltaic (PV) panels. This PV-EFR system exhibits a solar-to-chemical (STC) efficiency of 32.6% under AM 1.5 G simulated sunlight (100 mW cm-2), and high Faradaic efficiencies (FE, â¼ 67% for formic acid, and â¼90% for green hydrogen) with exceptional 120 h long-term stability in the STC mode. Such a photovoltaic-driven electrocatalytic strategy exhibits great potential for the rational utilization of renewable energy sources to produce high-value chemicals and fuels by upconversion of waste plastics.
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Intestinal epithelial barrier defects occur commonly during a variety of pathological conditions, though their underlying mechanisms are not completely understood. Sphingosine-1-phosphate (S1P) has been shown to be a critical regulator of proliferation and of maintenance of an intact intestinal epithelial barrier, as is also sphingosine kinase 1 (SphK1), the rate-limiting enzyme for S1P synthesis. SphK1 has been shown to modulate its effect on intestinal epithelial proliferation through increased levels of c-myc. We conducted genome-wide profile analysis to search for differential microRNA expression related to overexpressed SphK1 demonstrating adjusted expression of microRNA 542-5p (miR-542-5p). Here, we show that miR-542-5p is regulated by SphK1 activity and is an effector of c-myc translation that ultimately serves as a critical regulator of the intestinal epithelial barrier. miR-542-5p directly regulates c-myc translation through direct binding to the c-myc mRNA. Exogenous S1P analogs administered in vivo protect murine intestinal barrier from damage due to mesenteric ischemia reperfusion, and damaged intestinal tissue had increased levels of miR-542-5p. These results indicate that miR-542-5p plays a critical role in the regulation of S1P-mediated intestinal barrier function, and may highlight a novel role in potential therapies.
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Intestinos , MicroARNs , Animales , Ratones , Proliferación Celular/genética , Células Epiteliales/metabolismo , Lisofosfolípidos/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , EsfingosinaRESUMEN
The incidence of prostate cancer (PCa) in men globally increases as the standard of living improves. Blood serum biomarker prostate-specific antigen (PSA) detection is the gold standard assay that do not meet the requirements of early detection. Herein, a solution-gated graphene transistor (SGGT) biosensor for the ultrasensitive and rapid quantification detection of the early prostate cancer-relevant biomarker, miRNA-21 is reported. The designed single-stranded DNA (ssDNA) probes immobilized on the Au gate can hybridize effectively with the miRNA-21 molecules targets and induce the Dirac voltage shifts of SGGT transfer curves. The limit of detection (LOD) of the sensor can reach 10-20 M without amplification and any chemical or biological labeling. The detection linear range is from 10-20 to 10-12 M. The sensor can realize real-time detection of the miRNA-21 molecules in less than 5 min and can well distinguish one-mismatched miRNA-21 molecule. The blood serum samples from the patients without RNA extraction and amplification are measured. The results demonstrated that the biosensor can well distinguish the cancer patients from the control group and has higher sensitivity (100%) than PSA detection (58.3%). Contrastingly, it can be found that the PSA level is not directly related to PCa.
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Grafito , MicroARNs , Neoplasias de la Próstata , Masculino , Humanos , Antígeno Prostático Específico/genética , Grafito/química , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/genética , Biomarcadores de Tumor/genética , ADN de Cadena Simple , MicroARNs/genéticaRESUMEN
The ethyl acetate fraction of ethanol extract of Eucommiae Cortex can effectively inhibit joint inflammation and bone destruction in rats with collagen-induced arthritis(CIA) and has a potential therapeutic effect on rheumatoid arthritis. The triterpenoid(EU-Tid) and iridoid(EU-Idd) of Eucommiae Cortex are derivatives isolated from the ethyl acetate fraction of the ethanol extract of Eucommiae Cortex, and it is not clear whether they have inhibitory effects on joint inflammation and bone erosion in CIA rats. Therefore, based on the CIA model, the effects of EU-Tid, EU-Idd, and their combination(EU-TP) on arthritis in rats were observed, and the material basis of Eucommiae Cortex against arthritis was further clarified. The samples were collected two and four weeks after administration to observe the pathological changes in different stages of arthritis in CIA rats. For the rats in the model control group, with the prolongation of the disease course, the paw volume and arthritis score increased and histopathological lesions aggravated. Compared with the model control group, the drug administration groups showed reduced paw volumes and arthritis scores, and improved joint lesions and cartilage destruction. Additionally, the mRNA expression levels of tumor necrosis factor-α(TNF-α), interleukin-17(IL-17), and interleukin-23(IL-23) in the spleen were down-regulated in the drug administration groups. EU-TP and EU-Tid at concentrations of 160 and 320 µg·mL~(-1) could significantly inhibit the proliferation of human fibroblast-like synoviocytes-RA(HFLS-RA) and nitric oxide(NO) release in the supernatant of RAW264.7 cells induced by lipopolysaccharide(LPS) at the concentration range of 10-80 µg·mL~(-1) in vitro. EU-Idd had no effect on the proliferation of HFLS-RA but could reduce the NO release at concentrations of 40 and 80 µg·mL~(-1). The results indicated that the terpenoids of Eucommiae Cortex had great potential in the treatment of rheumatoid arthritis.
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Artritis Experimental , Artritis Reumatoide , Triterpenos , Ratas , Humanos , Animales , Artritis Experimental/tratamiento farmacológico , Iridoides/farmacología , Triterpenos/farmacología , Triterpenos/uso terapéutico , Artritis Reumatoide/inducido químicamente , Artritis Reumatoide/tratamiento farmacológico , Factor de Necrosis Tumoral alfa , Extractos Vegetales/farmacología , Inflamación/tratamiento farmacológico , Etanol , CitocinasRESUMEN
BACKGROUND: Peritonitis is the most common complication in patients undergoing peritoneal dialysis (PD). Most patients recover with appropriate antibiotic treatment; however, when peritonitis repeatedly relapses, the cause of recurrence must be explored. The relationship between atrial septal defect (ASD), infective endocarditis (IE), and peritonitis is rarely reported. Here, we present a case of recurrent peritonitis due to Staphylococcus aureus in a patient with ASD and IE undergoing PD. CASE PRESENTATION: A 46-year-old woman with chronic renal failure secondary to chronic glomerulonephritis experienced three episodes of peritonitis within 80 days of starting PD. The patient had a history of untreated ASD without symptoms. After undergoing PD for approximately 35 days, the patient was admitted to our hospital on April 5, 2016, due to abdominal pain and fever for 1 week (maximum temperature of 38.5 °C) accompanied by chills and shivering. The PD effluent from the time of her admission was positive for S. aureus. Thereafter, peritonitis recurred each month. When the third episode of peritonitis occurred, transthoracic echocardiography was performed, and a vegetation measuring 9.5 × 6.4 mm attached to the surface of the right ventricle around the ventricular septal membrane was identified. Finally, the patient was diagnosed with IE. Then, ASD repair surgery was successfully performed after the infection was controlled. The patient was followed up for 5 years, with no further episodes of recurrence. CONCLUSIONS: When a patient with ASD undergoing PD develops peritonitis, especially relapsing peritonitis, the possibility of IE is significantly increased. ASD repair surgery may be an important contributing factor to prevent peritonitis recurrence.
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Defectos del Tabique Interatrial , Diálisis Peritoneal , Peritonitis , Humanos , Femenino , Persona de Mediana Edad , Staphylococcus aureus , Recurrencia Local de Neoplasia/complicaciones , Diálisis Peritoneal/efectos adversos , Peritonitis/diagnóstico por imagen , Peritonitis/etiología , Antibacterianos/uso terapéutico , Defectos del Tabique Interatrial/complicaciones , Defectos del Tabique Interatrial/diagnóstico por imagen , Defectos del Tabique Interatrial/cirugíaRESUMEN
Objective: The objective of the study was to explore the CT and ultrasound features and clinical significance of perivascular epithelioid cell tumor (PEComa) of the liver. Methods: Eleven hepatic PEComa patients treated in our hospital were retrospectively analyzed based on the characteristics of the imaging results of the patients, including conventional ultrasound, CDFI, contrast-enhanced ultrasound (CEUS), and contrast-enhanced CT (CECT). Results: CT scans showed that all lesions were hypodense. Ultrasonography showed that lesions were either hyperechoic (4/11, 36.36%), hypoechoic (4/11, 36.36%), isoechoic (1/11, 9.09%), or heterogeneously echoic (2/11, 18.18%). CDFI showed that most of the lesions had an abundant blood supply (9/11, 81.82%). Whether on CT scan or ultrasonography, the margins of the lesions were dominated by clear margins. Ultrasonography revealed more features: hyperechoic patterns around lesions (3/11, 27.27%) and lateral shadow (5/11, 45.45%). The CDFI showed that large blood vessels were observed around the lesions (9/11, 81.82%). CECT shows two enhancement patterns: "fast in and fast out (FIFO)" (8/11, 72.72%) and "fast in and slow out (FISO)" (3/11, 27.27%). CEUS shows that all lesions had the enhancement pattern of "FISO," which was different from CECT. All lesions displayed rapid enhancement during HAP in CEUS during 7-20 s. Four patients (36.36%) washed out at 60-180 s, another four (36.36%) washed out at 180-300 s, and the remaining three patients (27.27%) showed no signs of washout even at 360 s. Conclusion: Some imaging features, such as clear margins, peripheral hyperechoic around the lesion, lateral shadow, the large blood vessels around lesions, and the "FISO" enhancement pattern, may indicate expansive growth of the tumor and be helpful in the diagnosis of PEComa. Ultrasound images may provide more details for clinical reference.
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OBJECTIVE: The aim of this study was to identify potentially important Rheumatoid arthritis (RA) targets related to immune cells based on bioinformatics analysis, and to identify small molecules of traditional Chinese medicine (TCM) associated with these targets that have potential therapeutic effects on RA. METHODS: Gene expression profile data related to RA were downloaded from the Gene Expression Omnibus (GSE55235, GSE55457, and GSE77298), and datasets were merged by the batch effect removal method. The RA key gene set was identified by protein-protein interaction network analysis and machine learning-based feature extraction. Furthermore, immune cell infiltration analysis was carried out on all DEGs to obtain key RA markers related to immune cells. Batch molecular docking of key RA markers was performed on our previously compiled dataset of small molecules in TCM using AutoDock Vina. Moreover, in vitro experiments were performed to examine the inhibitory effect of screened compounds on the synovial cells of an RA rat model. RESULTS: The PPI network and feature extraction with machine learning classifiers identified eight common key RA genes: MYH11, CFP, LY96, IGJ, LPL, CD48, RAC2, and CSK. RAC2 was significantly correlated with the infiltration and expression of five immune cells, with significant differences in these immune cells in the normal and RA samples. Molecular docking and in vitro experiments also showed that sanguinarine, sesamin, and honokiol could effectively inhibit the proliferation of RA rat synovial cells, also could all effectively inhibit the secretion of TNF-α and IL-1ß in synovial cells, and had a certain inhibitory effect on expression of the target protein RAC2. CONCLUSIONS: The core gene set of RA was screened from a new perspective, revealing biomarkers related to immune cell infiltration. Using molecular docking, we screened out TCM small molecules for the treatment of RA, providing methods and technical support for the treatment of RA with TCM.
Asunto(s)
Artritis Reumatoide , Biología Computacional , Animales , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/genética , Biomarcadores , Biología Computacional/métodos , Perfilación de la Expresión Génica/métodos , Redes Reguladoras de Genes , Medicina Tradicional China , Simulación del Acoplamiento Molecular , Ratas , Factor de Necrosis Tumoral alfaRESUMEN
BACKGROUND: Our previous data demonstrated that miR-19b expression was increased in human lung microvascular endothelial cells in-vitro-, in-vivo and in patients with hemorrhagic shock, leading to a decrease in syndecan-1 mRNA and protein and resulting in loss of endothelial barrier function. However, the mechanism underlying increased miR-19b expression remains unclear. The objective of the current study was to determine if c-Jun mediates the early responsive microRNA, miR-19b, to cause endothelial barrier dysfunction. METHOD: Human lung microvascular endothelial cells (HLMEC) or HEK293T cells were transfected with c-Jun overexpressing vector, c-Jun siRNA, miR-19b promoter vector, miR-19b mutated promoter vector, miR-19b oligo inhibitor, then subjected to hypoxia/reoxygenation as in-vitro model of hemorrhagic shock. Levels of protein, miRNA, and luciferase activity were measured. Transwell permeability of endothelial monolayers were also determined. Plasma levels of c-Jun were measured in injured patients with hemorrhagic shock. RESULT: Hypoxia/reoxygenation induced primary (pri-)miR-19b, mature miR-19b, and c-Jun expression over time in a comparable timeframe. c-Jun silencing by transfection with its specific siRNA reduced both pri-miR-19b and mature miR-19b levels. Conversely, c-Jun overexpression enhanced H/R-induced pri-miR-19b. Studies using a luciferase reporter assay revealed that in cells transfected with vectors containing the wild-type miR-19b promoter and luciferase reporter, c-Jun overexpression or hypoxia/ reoxygenation significantly increased luciferase activity. c-Jun knockdown reduced the luciferase activity in these cells, suggesting that the miR-19b promoter is directly activated by c-Jun. Further, chromatin immunoprecipitation assay confirmed that c-Jun directly bound to the promoter DNA of miR-19b and hypoxia/reoxygenation significantly increased this interaction. Additionally, c-Jun silencing prevented cell surface syndecan-1 loss and endothelial barrier dysfunction in HLMECs after hypoxia/reoxygenation. Lastly, c-Jun was significantly elevated in patients with hemorrhagic shock compared to healthy controls. CONCLUSION: Transcription factor c-Jun is inducible by hypoxia/reoxygenation, binds to and activates the miR-19b promoter. Using an in-vitro model of hemorrhagic shock, our findings identified a novel cellular mechanism whereby hypoxia/ reoxygenation increases miR-19b transcription by inducing c-Jun and leads to syndecan-1 decrease and endothelial cell barrier dysfunction. This finding supports that miR-19b could be a potential therapeutic target for hemorrhage shock.