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AIM: To evaluate the performances of the various estimated glomerular filtration rate (eGFR) equations of the Chronic Kidney Disease Epidemiology Collaboration, the Berlin Initiative Study (BIS), and the Full Age Spectrum (FAS) in older Chinese. METHODS: This study enrolled Chinese adults aged ≥ 65 years who underwent GFR measurements (via 99Tcm-DTPA renal dynamic imaging) in our hospital from 2011 to 2022. Using the measured glomerular filtration rate (mGFR) as the reference, we derived the bias, precision, accuracy, and consistency of each equation. RESULTS: We enrolled 519 participants, comprising 155 with mGFR ≥ 60 mL/min/1.73 m2 and 364 with mGFR < 60 mL/min/1.73 m2. In the total patients, the BIS equation based on creatinine and cystatin C (BIScr-cys) exhibited the lowest bias [median (95% confidence interval): 1.61 (0.77-2.18)], highest precision [interquartile range 11.82 (10.32-13.70)], highest accuracy (P30: 81.12%), and best consistency (95% limit of agreement: 101.5 mL/min/1.73 m2). In the mGFR ≥ 60 mL/min/1.73 m2 subgroup, the BIScr-cys and FAS equation based on creatinine and cystatin C (FAScr-cys) performed better than the other equations; in the mGFR < 60 mL/min/1.73 m2 subgroup, all equations exhibited relatively large deviations from the mGFR. Of all eight equations, the BIScr-cys performed the best. CONCLUSIONS: Although no equation was fully accurate in the mGFR < 60 mL/min/1.73 m2 subgroup, the BIScr-cys (of the eight equations) assessed the eGFRs of the entire population best. A new equation is urgently required for older Chinese and even East Asians, especially those with moderate-to-severe renal insufficiency.
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Cistatina C , Taxa de Filtração Glomerular , Idoso , Humanos , China , Creatinina , População do Leste AsiáticoRESUMO
An efficient and convenient method for the synthesis of phenols and aliphatic alcohols is described in this paper. The oxidative hydroxylation reaction of various organoboron compounds proceeded smoothly by employing H2O2 as the oxidant and citric acid as the catalyst in water at room temperature to produce phenols and aliphatic alcohols in satisfactory to excellent yields (up to 99% yield). Various synthetically useful functional groups, such as halogen atom, cyano, and nitro groups, remain intact during the oxidative hydroxylation. The developed catalytic system also could accommodate phenylboronic pinacol ester and potassium phenyltrifluoroborate to give the target product good yields.
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BACKGROUND: Osteosarcoma is a malignancy that normally affects children, adolescents, and young adults. Although accumulating evidence has demonstrated the importance of HULC in osteosarcoma, little is reported about its functional roles and molecular mechanisms. METHODS: The expression of HULC and miR-372-3p in osteosarcoma tissues was quantified by qRT-PCR. The regulatory roles of HULC and miR-372-3p on cell proliferation, apoptosis, migration and invasion were determined by CCK-8, colony formation, flow cytometry, wound healing, and transwell assays, respectively. The bioinformatics prediction software RAID v2.0 was used to predict the putative binding sites. The interactions among HULC, miR-372-3p and HMGB1 were explored by luciferase assay and western blot assay. RESULTS: Our results revealed elevated HULC and decreased miR-372-3p expression in both osteosarcoma tissues and cell lines. Overexpression of HULC or knockdown of miR-372-3p promoted osteosarcoma cell proliferation, migration and invasion and induced cell apoptosis. Bioinformatics and luciferase assays verified that HULC directly interacted with miR-372-3p to attenuate miR-372-3p binding to the HMGB1 3'-UTR. Furthermore, mechanistic investigations confirmed that activation of the miR-372-3p/HMGB1 regulatory loop by knockdown of miR-372-3p or overexpression of HMGB1 reversed the in vitro roles of HULC in promoting osteosarcoma cell proliferation, migration and invasion. CONCLUSION: Our study is the first to demonstrate that HULC may act as a ceRNA to modulate HMGB1 expression by competitively sponging miR-372-3p, leading to the regulation of osteosarcoma progression, which provides new insight into osteosarcoma diagnosis and treatment.
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Neoplasias Ósseas/patologia , Proteína HMGB1/genética , MicroRNAs/genética , Osteossarcoma/patologia , RNA Longo não Codificante/genética , Animais , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Proteína HMGB1/metabolismo , Humanos , Camundongos , Invasividade Neoplásica , Transplante de Neoplasias , Osteossarcoma/genética , Osteossarcoma/metabolismo , Transdução de SinaisRESUMO
In this editorial, we commented on the article by Akers et al published in the recent issue of the World Journal of Clinical Cases. We focused specifically on the role of the transcription factor paired box protein 8 (PAX8) belonging to the family PAX in the carcinogenesis of a gynecologic tumor, endocervical adenocarcinoma, arising from the tissue of mesonephric origin, and the potential diagnostic value for the same type of neoplasms. The global vaccination program of human papillomavirus (HPV) has dramatically reduced the incidence of cervical cancer, including cases of adenocarcinoma. The type of adenoid epithelial origin has a lower frequency of HPV detection but tends to be more aggressive and fatal. Cases of endocervical adenocarcinoma occurring in females of menopause age have been described in the 2023 volume of the World Journal of Clinical Cases and in our study recently published in Oncol Lett. The histopathological findings and immunohistochemical assays showed that the lesions had glandular morphology, and the specimens in these two reports were immunohistochemically positive for the transcription factor PAX8, albeit that they had opposing expression profiles of tumor suppressor p16 and estrogen receptor and the presence of the HPV genome. The presence of a mucin protein, MUC 5AC, as revealed in both studies suggested target molecules for the diagnosis of mucinous adenoid type of uterine tumor and other histological origins. The clinical outcome was unfavorable due to metastasis and recurrence. This prompted the improvement of the antitumor modality, with the introduction of precise targeting therapy. Mucin has now been reported to be the therapeutic target for adenocarcinomas.
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China is the largest mariculture country, and shellfish and algae output ranks first, showing high carbon sink capacity. In recent years, the single cultivation of macroalgae (Pyropia yezoensis) has been changed to macroalgae-shellfish mariculture in Haizhou Bay to increase the yield of P. yezoensis and improve the water environment quality. In this study, four surveys were carried out in July 2022 during the monoculture period of oyster (Magallana gigas), as well as at different stages of P. yezoensis culture (head-crop period, November 2022, peak growing season, January 2023, and end of harvesting, March 2023) in the mariculture and the surrounding waters of Haizhou Bay. The effects of different stages of culture on the seawater environment and seasonal and spatial variations in the carbonate system were analyzed, and the carbon sink capacity was preliminarily estimated. The results showed that in summer, the calcification of M. gigas and the primary production process of phytoplankton effectively reduced the dissolved inorganic carbon (DIC) level in the culture area. The culture area acts as a CO2 sink, with an average air-sea CO2 flux of -4.5 mmol m-2 d-1. During the polyculture period, the P. yezoensis culture activities maintained the stability of the seawater carbonate system, and the culture area shows strong CO2 sinks, with the average air-sea CO2 flux of -24.10 mmol m-2 d-1, -37.68 mmol m-2 d-1, and -38.99 mmol m-2 d-1, respectively. The absorption of CO2 by large-scale cultured P. yezoensis through the "biological pump" effect is the main factor affecting the CO2 exchange process at the air-sea interface, and the absorption rate of CO2 by P. yezoensis at the mature stage is higher than that at the growth stage before harvesting. The study revealed that macroalgae-shellfish mariculture could promote mutual growth, alleviate environmental pressure, and enhance the carbon sink of the culture area. The relationship between mariculture and the carbon cycle of a mariculture ecosystem is very complicated, and its biochemical process should be given great attention for further study.
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BACKGROUND: Hepatic epithelioid angiomyolipoma (HEA) has a low incidence and both clinical manifestations and imaging lack specificity. Thus, it is easy to misdiagnose HEA as other tumors of the liver, especially in the presence of liver diseases such as hepatitis cirrhosis. This article reviewed the diagnosis and treatment of a patient with HEA and alcoholic cirrhosis, and analyzed the literature, in order to improve the understanding of this disease. CASE SUMMARY: A 67-year-old male patient with a history of alcoholic cirrhosis was admitted due to the discovery of a space-occupying lesion in the liver. Based on the patient's history, laboratory examinations, and imaging examinations, a malignant liver tumor was considered and laparoscopic partial hepatectomy was performed. Postoperative pathology showed HEA. During outpatient follow-up, the patient showed no sign of recurrence. CONCLUSION: HEA is difficult to make a definite diagnosis before surgery. HEA has the potential for malignant degeneration. If conditions permit, surgical treatment is recommended.
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Methamphetamine (MA) is one of the most abused drugs globally, but the mechanism of its addiction remains unclear. Several animal studies have shown that the gut microbiota (GM) influences addictive behaviors, but the pattern of GM changes during addiction in animals of different species remains unclear. The aim of this study was to explore the association between dynamic changes in GM and MA self-administration acquisition among two classical mammals, rhesus monkeys (Macaca mulatta) and rats, MA self-administration models. Male Sprague-Dawley rats and male rhesus monkeys were subjected to classical MA self-administration training, and fecal samples were collected before and after MA self-administration training, respectively. 16S rRNA sequencing was used for GM analyses. We found that GM changes were more pronounced in rats than in rhesus monkeys, as evidenced by more GM taxa producing significant differences before and after MA self-administration training in rats than in monkeys. We also found that the expression of the genus Clostridia_vadinBB60_group significantly decreased after MA self-administration training in both rats and rhesus monkeys. Lactobacillus changes were significantly negatively correlated with total MA uptake in rats (Pearson R = - 0.666, p = 0.035; Spearman R = - 0.721, p = 0.023), whereas its change was also highly negatively correlated with total MA uptake in rhesus monkeys (Pearson R = - 0.882, p = 0.118; Spearman R = - 1.000, p = 0.083), although this was not significant. These findings suggest that MA causes significant alterations in GM in both rhesus monkeys and rats and that the genus Lactobacillus might be a common therapeutic target for MA uptake prevention across the species.
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OBJECTIVES: Metabolic-associated fatty liver disease (MAFLD) has clinical relevance in patients with acute-on-chronic liver failure (ACLF). We investigated the association between MAFLD and prognosis in patients with ACLF. METHODS: We included patients with ACLF with available clinical data who visited our hospital for nearly 9 years. We compared the prognosis of patients in the different subgroups of ACLF and predicted the incidence of adverse outcomes. Moreover, a new model based on MAFLD was established. RESULTS: Among 339 participants, 75 had MAFLD. The prognosis of patients with ACLF was significantly correlated with MAFLD. Patients with ACLF with concomitant MAFLD tended to have a lower cumulative survival rate (p = 0.026) and a higher incidence of hepatorenal syndrome (9.33% versus 3.40%, p = 0.033) than those without MAFLD. We developed an TIM2 model and the area under the ROC curve of the new model for 30-day and 60-day mortality (0.759 and 0.748) was higher than other predictive methods. CONCLUSION: The presence of MAFLD in patients with HBV-related ACLF was associated with an increased risk of in-hospital mortality. Moreover, The TIM2 model is a high-performance prognostic score for HBV-related ACLF.
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Insuficiência Hepática Crônica Agudizada , Hepatopatia Gordurosa não Alcoólica , Humanos , Insuficiência Hepática Crônica Agudizada/diagnóstico , Insuficiência Hepática Crônica Agudizada/etiologia , Vírus da Hepatite B , Prognóstico , Curva ROC , Hepatopatia Gordurosa não Alcoólica/complicações , Estudos RetrospectivosRESUMO
BACKGROUND: Tenofovir alafenamide (TAF) has a serum lipid-raising effect in patients with HIV; however, its effect on serum lipids and nonalcoholic fatty liver disease (NAFLD) risk in patients with chronic hepatitis B (CHB) is unclear. AIM: To compare the effects of TAF and entecavir (ETV) on serum lipid levels in patients with CHB. METHODS: In this retrospective cohort study, the data including the clinical features, serum lipids, and metabolic factors of patients with CHB at baseline and approximately 1 year after TAF or ETV treatment were collected and analyzed. We used propensity score-matched models to assess the effects on high-density lipoprotein, low-density lipoprotein, triglycerides, and total cholesterol (TCHO). RESULTS: A total of 336 patients (75.60% male) were included; 63.69% received TAF and 36.31% received ETV. Compared with the ETV group, the TAF group had significantly higher TCHO levels after treatment (4.67 ± 0.90 vs 4.36 ± 1.05, P = 0.006). In a propensity score-matched model for body mass index, age, sex, smoking, drinking, presence of comorbidities such as NAFLD, cirrhosis, diabetes mellitus, and hypertension, TAF-treated patients had significantly increased TCHO levels compared to that at baseline (P = 0.019). There was no difference for the ETV group. Body mass index, sex, hypertension, baseline TCHO, and creatine kinase-MB isoenzyme levels were significantly associated with elevated TCHO levels in logistic regression analysis. However, 1-year TAF treatment did not increase the incidence of NAFLD. CONCLUSION: A greater increase in TCHO was observed in patients with CHB receiving TAF compared to those receiving ETV. However, TAF-induced dyslipidemia did not increase the incidence of NAFLD.
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PURPOSE: The aim of this study was to investigate the genetic polymorphisms of UGT1A3, UGT1A6, and UGT2B7 in Chinese epilepsy patients and their potential influence on the pharmacokinetics of valproic acid (VPA). METHODS: The genetic architectures of UGT1A3, UGT1A6, and UGT2B7 in 242 epilepsy patients were detected by DNA sequencing and PCR-restriction fragment length polymorphism. Steady-state plasma concentrations of VPA in 225 patients who had received VPA (approx. 250-1,000 mg/day) for at least 2 weeks were determined and associated with UGT polymorphisms. RESULTS: The allelic distribution of UGT1A3 in our Chinese epilepsy patients was significantly different from that in healthy subjects based on reference data. The standardized trough plasma concentration (C(S)) of VPA was much lower in our patients with the UGT1A3*5 variant than in the wild type carriers (3.24 ± 1.05 vs. 4.68 ± 1.24 µg·kg·mL(-1)·mg(-1), P < 0.01). UGT polymorphisms had no influence on the pharmacokinetic interactions between carbamazepine and VPA. CONCLUSION: Our results suggest that UGT1A3*5 may be an important determinant of individual variability in the pharmacokinetics of VPA and that it may be necessary to increase VPA dose for UGT1A3*5 carriers to ensure its therapeutic range of 50-100 µg/mL.
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Epilepsia/tratamento farmacológico , Epilepsia/genética , Glucuronosiltransferase/genética , Glucuronosiltransferase/metabolismo , Ácido Valproico/farmacocinética , Adulto , Alelos , Anticonvulsivantes/sangue , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/uso terapêutico , Povo Asiático , Carbamazepina/uso terapêutico , Epilepsia/enzimologia , Feminino , Haplótipos , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA/métodos , Ácido Valproico/sangue , Ácido Valproico/uso terapêuticoRESUMO
Microglia is activated and polarized to proinflammatory M1 phenotype or antiinflammatory M2 phenotype in neuroinflammation. Apelin13 exerts protective properties against neuroinflammation in several neurological disorders. We aimed to investigate whether apelin13 played a protective role on BV2 microglia and explore its underlying mechanisms. Lipopolysaccharide (LPS)stimulated BV2 microglia cells were treated with apelin13. Microglia activation was evaluated by immunofluorescence with Factin. Western blot was performed to measure the expression of autophagy associated proteins. CD16/32 and CD206 were detected to assess microglia polarization by western blot and flow cytometry. qRTPCR was utilized to measure inducible nitric oxide synthase (iNOS), arginase1 (Arg1), interleukin10 (IL10), interleukin6 (IL6) and tumor necrosis factoralpha (TNFα). Histone H3 acetyl lysine 9 (H3K9ac) enrichment of TNFα and IL6 promoter was detected by ChIP. We discovered that apelin13 impacted the actin cytoskeleton, recovering the control phenotype following LPS exposure. Apelin13 improved autophagymediated microglia polarization towards M2 phenotype to alleviate inflammatory response in LPSstimulated cells. Autophagy flux inhibitor chloroquine antagonized these effects of apelin13 on LPSstimulated cells. Besides, apelin13 decreased the enrichment of H3K9ac at the promoter region of TNFα and IL6 to inhibit inflammatory response, which was reversed by histone deacetylase antagonist valproate. Taken together, apelin13 alleviated inflammation via facilitating microglia M2 polarization due to autophagy promotion, and inhibiting H3K9ac enrichment on promoter regions of TNFα and IL6.
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Lipopolissacarídeos , Microglia , Autofagia , Peptídeos e Proteínas de Sinalização Intercelular , Interleucina-6/metabolismo , Lipopolissacarídeos/efeitos adversos , Microglia/metabolismo , Regiões Promotoras Genéticas , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
Three novel fluoranthene dyes were obtained by cycloaddition reactions using acrylonitrile and dialkyl acetylenedicarboxylates. Their fluorescence properties in different polar-organic solvents were investigated systematically. Meanwhile, spectral changes induced by the addition of water in methanol were observed, indicating that these fluoranthenes dyes can be efficiently used to detect the water content in methanol as probes. Significantly, the practical test measurements for the water contents in methanol illustrated the measured results with the three fluorescent probes were basically consistent with the water content added artificially. This demonstrated the potential of these fluoranthene dyes as probes in measuring the water content in methanol.
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OBJECTIVE: To study the condylar position of post-orthodontic patients with class II malocclusion. METHODS: Forty four patients with class II malocclusion were recruited, among whom 22 were given orthodontic treatment and 22 without any treatment as controls. The condylar distractions between centric relation (CR) and centric occlusion (CO) were measured by an Panadent articulator with Measurement of Condylar Displacement (MCD). RESULTS: There was no significant difference in condylar position between the two groups. Most condylar distractions happened to the posterior-inferior direction and were clinically acceptable. The amount of distractions was not correlated with Class II elastics. CONCLUSION: There is no enough evidence to show that traditional orthodontic treatment impacts the condylar position in patients with Class II malocclusion. However, attention still needs to be paid to condylar position in order to achieve a functional occlusion.
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Má Oclusão Classe II de Angle/patologia , Côndilo Mandibular/anatomia & histologia , Ortodontia Corretiva , Adolescente , Criança , Feminino , Humanos , Masculino , Má Oclusão Classe II de Angle/terapia , Côndilo Mandibular/patologia , Côndilo Mandibular/fisiologiaRESUMO
Calenduloside E (CE) is a natural triterpenoid saponin isolated from Aralia elata (Miq.) Seem., a well-known traditional Chinese medicine. Our previous studies have shown that CE exerts cardiovascular protective effects both in vivo and in vitro. However, its role in myocardial ischemia/reperfusion injury (MIRI) and the mechanism involved are currently unknown. Mitochondrial dynamics play a key role in MIRI. This study investigated the effects of CE on mitochondrial dynamics and the signaling pathways involved in myocardial ischemia/reperfusion (MI/R). The MI/R rat model and the hypoxia/reoxygenation (H/R) cardiomyocyte model were established in this study. CE exerted significant cardioprotective effects in vivo and in vitro by improving cardiac function, decreasing myocardial infarct size, increasing cardiomyocyte viability, and inhibiting cardiomyocyte apoptosis associated with MI/R. Mechanistically, CE restored mitochondrial homeostasis against MI/R injury through improved mitochondrial ultrastructure, enhanced ATP content and mitochondrial membrane potential, and reduced mitochondrial permeability transition pore (MPTP) opening, while promoting mitochondrial fusion and preventing mitochondrial fission. However, genetic silencing of OPA1 by siRNA abolished the beneficial effects of CE on cardiomyocyte survival and mitochondrial dynamics. Moreover, we demonstrated that CE activated AMP-activated protein kinase (AMPK) and treatment with the AMPK inhibitor, compound C, abolished the protective effects of CE on OPA1 expression and mitochondrial function. Overall, this study demonstrates that CE is effective in mitigating MIRI by modulating AMPK activation-mediated OPA1-related mitochondrial fusion.
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Proteínas Quinases Ativadas por AMP/metabolismo , GTP Fosfo-Hidrolases/metabolismo , Mitocôndrias Cardíacas/metabolismo , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/enzimologia , Ácido Oleanólico/análogos & derivados , Saponinas/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Cardiotônicos/farmacologia , Cardiotônicos/uso terapêutico , Linhagem Celular , Inativação Gênica/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Masculino , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/ultraestrutura , Dinâmica Mitocondrial/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Ácido Oleanólico/farmacologia , Ácido Oleanólico/uso terapêutico , Ratos Sprague-Dawley , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: To explore the effect and mechanism of miR-16-5p on neuron apoptosis and inflammatory response induced by spinal cord injury (SCI). METHODS: Allen's weight-drop method and Basso Bcattie Bresnahan (BBB) rating scale were used to establish SCI rat model and assess locomotor function, respectively. Histopathology of SCI rats and Sham-operated rats was validated by hematoxylin and eosin (H&E) staining. After intravenous injection of miR-16-5p agomir, miR-16-5p antagomir, pcDNA3.1-Apelin-13 or negative controls into SCI rat tails, neuron apoptosis and the expression of miR-16-5p, Apelin-13, apoptotic proteins, inflammatory response-related proteins and ERK1/2 pathway-related protein were detected. Dual luciferase reporter gene assay was applied for identifying the binding between miR-16-5p and Apelin-13. RESULTS: SCI rats had locomotor impairment with markedly edema and hemorrhage. Upregulated miR-16-5p expression and downregulated Apelin-13 expression were presented in SCI rats. Intravenous injection of miR-16-5p antagomir or/and pcDNA3.1-Apelin-13 could increase the expression of anti-apoptotic proteins (Bcl-2 and Mcl-1) and p-ERK1/2 expression while decrease the expression of pro-apoptotic proteins (cleaved caspase-3 and Bax) and inflammatory response-related proteins (TNF-α, IL-1ß and IL-6). The reverse pattern was shown in rats injected with miR-16-5p agomir. MiR-16-5p targeted Apelin-13. Promotion of miR-16-5p agomir on SCI was attenuated by injection of agomir + pcDNA3.1-Apelin-13. CONCLUSIONS: Downregulation of miR-16-5p could upregulate Apelin-13 expression to activate ERK1/2 pathway, thus alleviating SCI-induced neuron apoptosis and inflammatory response.
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AIMS: Hyperbilirubinemia is associated with postoperative acute kidney injury in patients undergoing cardiac surgeries. A high concentration of bilirubin could induce oxidative stress and cell apoptosis. The aim of this study was to investigate whether hyperbilirubinemia aggravated the renal tubule cells injury and the pro-apoptotic potential of bilirubin on renal ischemia reperfusion injury (RIRI). METHODS: The human proximal tubular epithelial cell line HK-2 cells were challenged with a gradient concentration of bilirubin for 24 h. Cell injury was assessed by flow cytometry and MTT assay. Bilirubin was injected intraperitoneally into male Sprague-Dawley rats once every 12 h (100 mg/kg), 3 times in total. The same solvent volume without bilirubin powder was used as vehicle in non-bilirubin injection groups. The RIRI surgical procedure was a bilateral renal pedicles clamping (45 min) followed by 30 h reperfusion. The rats were divided into 4 groups: negative control (NC), similar surgical procedures without clamping; Bil, bilirubin injection for 36 h, then rats were sacrificed; RIRI, RIRI surgical procedures; Bil + RIRI, RIRI applied 6 h later than the first bilirubin injection, rats were sacrificed after another 30 h. RESULTS: In vitro, bilirubin induced cell apoptosis and significantly decreased the cell viability of HK-2 cells. Bilirubin induced the active caspase 3 and phosphorylation of p38 in HK-2 cells. In vivo, serum creatinine was higher in Bil + RIRI compared with RIRI (p < 0.01). The tubular injury scores of hematoxylin and eosin and tubular necrosis scores of periodic acid-Schiff were higher in Bil + RIRI than these in RIRI (All p < 0.05). The number of Tunel-positive nuclei was higher in Bil + RIRI compared to RIRI (p < 0.001). The active caspase 3 and phosphorylation of p38 were higher and the Bcl2 was lower in Bil + RIRI compared to RIRI. Moreover, the apoptosis level was higher in Bil compared to NC. CONCLUSIONS: Our results reveal that the hyperbilirubinemia induces pro-apoptotic effects and aggravates RIRI.
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Apoptose , Hiperbilirrubinemia/patologia , Traumatismo por Reperfusão/patologia , Animais , Bilirrubina/sangue , Linhagem Celular , Creatinina/sangue , Humanos , Túbulos Renais/patologia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
We have previously reported that the 3p21 tumor suppressor BLU regulates cell cycle by blocking JNK/MAPK signaling. Another member of the MAPK family, extracellular signal response kinase (ERK), is induced by the RAS-RAF-MEK-ERK pathway and is targeted in anticancer therapy. The effects of BLU on tumor growth were evaluated by measuring the size of nasopharyngeal carcinoma (NPC) xenografted tumors intra-tumorally injected with BLU adenovirus 5 (BLU Ad5) and the viability of NPC cells transferred with BLU. Tumor size was correlated with downregulation of the ERK pathway by BLU. Phosphorylation of ERK and Elk reporter activities were assayed. The regulated cyclins D1 and B1 were measured by CCND1 and CCNB1 gene promoter activity by co-transfection of BLU, RAS V12G, together with BLU+RAS V12G, pCD316+RAS V12G. The cell cycle phase distribution was determined by FACS-based DNA content assay. The data showed that growth of the xenografted tumor was inhibited and viability of HONE-1 cells was reduced by recombinant BLU. BLU down-regulated ERK signaling by reducing protein substrate phosphorylation, inhibiting Elk reporter activity, and blocking promoter activities of the CCND1 gene and reduced cyclins D1 expression to arrest the cell cycle at the G1 phase. The population of G2/M cells was also remarkably decreased. HRAS V12G activated ERK and cyclin D1 and B1 promoters, and the effects were antagonized by BLU. Taken together, our results suggested that BLU inhibited ERK signaling, downregulated cyclins D1 and B1, and prevented cell cycle progression through interfering with HRAS V12G signaling to exert tumor suppression.
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Polymeric materials have been widely used in the fabrication of data-storage devices, owing to their unique advantages and defined conduction mechanisms. To date, the most-functional polymers that have been reported for memory devices were synthesized through random copolymerization, whilst there have been no reports regarding the memory effect of block polymers. Herein, we synthesized a random copolymer (PMCz8 -co-PMBNa2 ) and its corresponding block copolymer (PMCz8 -b-PMBNa2 ) to study the effect of the method of polymerization on the memory properties of the corresponding devices. Interestingly, both devices (ITO/PMCz8 -co-PMBNa2 /Al and ITO/PMCz8 -b-PMBNa2 /Al) exhibited ternary memory performance, with threshold voltages of -1.7â V/-3.3â V and -2.7â V/-3.8â V, respectively. However, based on comprehensive measurements, the memory properties of PMCz8 -co-PMBNa2 and PMCz8 -b-PMBNa2 were found to be owing to the operation of different conduction mechanisms, which resulted from different molecular stacking in the film state. Therefore, we expect that this work will be helpful for improving our understanding of the conduction mechanisms in polymer-based data-storage devices.
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A Lewis-acid catalyzed intermolecular Diels-Alder reaction between multisubstituted acyclic dienes and the E and Z isomers of α,ß-enals was studied. It was found that the diene reacted selectively with the Z-isomer of the α,ß-enal.
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OBJECTIVE: To improve Luo-Ye pump-based stress-forming system and optimize the stimulating effect on smooth muscle cells during cultivation of tissue-engineered blood vessels (TEBV). METHODS: A new Luo-Ye pump-based TEBV 3D culture system was developed by adding an air pump to the output of the bioreactor. A pressure guide wire was used to measure the stress at different points of the silicone tube inside the TEBV bio-reactor, and fitting curves of the stress changes over time was created using Origin 8.0 software. The TEBVs were constructed by seeding vascular smooth muscle cells (VSMCs) isolated from human umbilical artery on polyglycolic acid (PGA) and cultured under dynamic conditions with 40 mmHg resistance (improved group), dynamic conditions without resistance (control group) or static condition (static group) for 4 weeks. The harvested TEBVs were then examined with HE staining, masson staining, α-SMA immunohistochemical staining, and scanning and transmission electron microscopy with semi-quantitative analysis of collagen content and α-SMA expression. RESULTS: The measured stress values and the fitting curves showed that the stress stimuli from the Luo-Ye pump were enhanced by adding an air pump to the output of the bioreactor. Histological analysis revealed improved VSMC density, collagen content and α-SMA expression in the TEBVs constructed with the improved method as compared with those in the control and static groups. CONCLUSION: Adding an air pump to the Luo-Ye pump significantly enhances the stress stimulation in the TEBV 3-D culture system to promote the secretion function of VSMCs.