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1.
Ann Med ; 56(1): 2389470, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39126262

RESUMEN

BACKGROUND: Previous meta-analyses have investigated the efficacy of lipid-lowering therapies for atherosclerotic cardiovascular disease; however, few have focused on patients with acute coronary syndrome (ACS). This meta-analysis aimed to compare the benefits of intensive lipid-lowering therapy with those of background statin therapy in patients with ACS. METHODS: Searches were performed on PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases for articles published until April 13, 2023. Randomized controlled trials that compared intensive lipid-lowering therapies and background statin therapies in patients with prior ACS and recorded the outcome of three-point major cardiovascular events (MACE) were included. The risk ratio (RR) with 95% confidence interval (CI) was used as a measure of primary and secondary outcomes. RESULTS: Nine trials involving 38,640 patients with ACS were identified. Pooled results suggested that intensive lipid-lowering therapies are associated with a reduction in the risk of three-point MACE (RR, 0.88; 95% CI, 0.83-0.94; p < 0.001), recurrent ACS (RR, 0.82; 95% CI, 0.71-0.96; p = 0.013), nonfatal myocardial infarction (MI) (RR, 0.87; 95% CI, 0.81-0.93; p < 0.001), stroke (RR, 0.83; 95% CI, 0.73-0.94; p = 0.003), and unstable angina-related hospitalization (RR, 0.57; 95% CI, 0.33-0.99; p = 0.046), but not all-cause mortality (RR, 0.94; 95% CI, 0.82-1.07; p = 0.329), cardiovascular disease-related mortality (RR, 0.96; 95% CI, 0.88-1.06; p = 0.457) or coronary revascularization (RR, 0.89; 95% CI, 0.79-1.00; p = 0.057). CONCLUSIONS: Intensive lipid-lowering therapies may reduce the risk of three-point MACE, recurrent ACS, nonfatal MI, stroke, and hospitalization for unstable angina in patients with ACS undergoing background statin therapy. These results may assist in clinical decision-making for the secondary prevention of cardiovascular events to initiate intensive lipid-lowering therapies immediately after ACS.


Asunto(s)
Síndrome Coronario Agudo , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/mortalidad , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Hipolipemiantes/uso terapéutico , Hipolipemiantes/administración & dosificación , Infarto del Miocardio/epidemiología , Infarto del Miocardio/prevención & control , Resultado del Tratamiento , Hospitalización/estadística & datos numéricos , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/epidemiología
2.
Int J Mol Sci ; 25(10)2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38791176

RESUMEN

Extensive microbial interactions occur within insect hosts. However, the interactions between the Huanglongbing (HLB) pathogen and endosymbiotic bacteria within the Asian citrus psyllid (ACP, Diaphorina citri Kuwayama) in wild populations remain elusive. Thus, this study aimed to detect the infection rates of HLB in the ACP across five localities in China, with a widespread prevalence in Ruijin (RJ, 58%), Huidong (HD, 28%), and Lingui (LG, 15%) populations. Next, microbial communities of RJ and LG populations collected from citrus were analyzed via 16S rRNA amplicon sequencing. The results revealed a markedly higher microbial diversity in the RJ population compared to the LG population. Moreover, the PCoA analysis identified significant differences in microbial communities between the two populations. Considering that the inter-population differences of Bray-Curtis dissimilarity in the RJ population exceeded those between populations, separate analyses were performed. Our findings indicated an increased abundance of Enterobacteriaceae in individuals infected with HLB in both populations. Random forest analysis also identified Enterobacteriaceae as a crucial indicator of HLB infection. Furthermore, the phylogenetic analysis suggested a potential regulatory role of ASV4017 in Enterobacteriaceae for ACP, suggesting its possible attractant activity. This research contributes to expanding the understanding of microbial communities associated with HLB infection, holding significant implications for HLB prevention and treatment.


Asunto(s)
Enterobacteriaceae , Hemípteros , Filogenia , Enfermedades de las Plantas , ARN Ribosómico 16S , Animales , Hemípteros/microbiología , Enterobacteriaceae/genética , Enterobacteriaceae/clasificación , Enterobacteriaceae/patogenicidad , ARN Ribosómico 16S/genética , Enfermedades de las Plantas/microbiología , China/epidemiología , Citrus/microbiología , Microbiota
3.
J Colloid Interface Sci ; 662: 786-795, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38382363

RESUMEN

Copper-based tandem catalysts are effective candidates for yielding multi-carbon (C2+) products in electrochemical reduction of carbon dioxide (CO2RR). However, these catalysts still face a significant challenge regarding in the low selectivity for the production of a specific product. In this study, we report a high selectivity of 77.8 %±2 % at -1.0 V (vs RHE) for the production of C2H4 by using a Cu88Ag12NW catalyst which is primarily prepared through a combined Cu-Ag co-deposition and wet chemical method, employing an attractive strategy focused on regulating the microenvironment over Cu-Ag nanowires. The experimental and computational studies show that the higher *CO coverage and lower intermediate adsorption energy are important reasons for achieving the high C2H4 selectivity of Cu88Ag12NW catalyst. Comsol simulation results indicate that dense nanowires exhibit a nano-limiting effect on OH- ions, thereby leading to an increase in local pH and promoting coupling reactions. The catalyst demonstrates no noticeable decrease in current density or selectivity even after 12 h of continuous operation. The Cu-Ag nanowire composite exhibits remarkable catalytic activity, superior faradaic efficiency, excellent stability, and easy synthesis, which highlights its significant potential for electro-reducing carbon dioxide into valuable products.

4.
J Neurosci Methods ; 403: 110049, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38151187

RESUMEN

BACKGROUND: Dynamic spatial functional network connectivity (dsFNC) has shown advantages in detecting functional alterations impacted by mental disorders using magnitude-only fMRI data. However, complete fMRI data are complex-valued with unique and useful phase information. METHODS: We propose dsFNC of spatial source phase (SSP) maps, derived from complex-valued fMRI data (named SSP-dsFNC), to capture the dynamics elicited by the phase. We compute mutual information for connectivity quantification, employ statistical analysis and Markov chains to assess dynamics, ultimately classifying schizophrenia patients (SZs) and healthy controls (HCs) based on connectivity variance and Markov chain state transitions across windows. RESULTS: SSP-dsFNC yielded greater dynamics and more significant HC-SZ differences, due to the use of complete brain information from complex-valued fMRI data. COMPARISON WITH EXISTING METHODS: Compared with magnitude-dsFNC, SSP-dsFNC detected additional and meaningful connections across windows (e.g., for right frontal parietal) and achieved 14.6% higher accuracy for classifying HCs and SZs. CONCLUSIONS: This work provides new evidence about how SSP-dsFNC could be impacted by schizophrenia, and this information could be used to identify potential imaging biomarkers for psychotic diagnosis.


Asunto(s)
Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Mapeo Encefálico/métodos , Encéfalo/diagnóstico por imagen , Cadenas de Markov
5.
Funct Integr Genomics ; 23(2): 170, 2023 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-37209314

RESUMEN

As a toxic heavy metal, cadmium (Cd) is one of the principal pollutants influencing rice productivity and food security. Despite several studies, the underlying mechanism of Cd response in plants remains largely unclear. Dehydrins are part of the late embryogenesis abundant (LEA) family which protect plants against abiotic stresses. In this study, a Cd-responsive LEA gene, OsDHN2, was functionally characterized. The chromosome localization results indicated that OsDHN2 was located on chromosome 2 of rice. Meanwhile, cis-acting elements, such as MBS (MYB binding site involved in drought-inducibility), ARE (anaerobic induction), and ABRE (abscisic acid), were present in the OsDHN2 promoter region. Expression pattern analysis also showed that OsDHN2 expression was induced in both roots and shoots under Cd stress. Overexpression of OsDHN2 improved Cd tolerance and reduced Cd concentration in yeast. Moreover, increased expression levels of SOD1, CTA1, GSH1, or CTT1 were found in transgenic yeast under Cd stress, suggesting the increased antioxidant enzymatic activities. These results suggested that OsDHN2 is a Cd-responsive gene that has the potential to improve resistance to Cd in rice.


Asunto(s)
Cadmio , Oryza , Cadmio/toxicidad , Cadmio/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Oryza/genética , Oryza/metabolismo , Biología Computacional , Regulación de la Expresión Génica de las Plantas
6.
Chinese Journal of Surgery ; (12): 100-106, 2023.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-970192

RESUMEN

Objectives: To establish a newly-designed scoring system for breast imaging-reporting and data system (BI-RADS) 4 and 5 breast lesions only visible on MRI, and to examine their clinical pathway of biopsy. Methods: The BI-RADS 4 and 5 breast lesions only visible on MRI but not suspected on mammograms or ultrasound between June 2007 and December 2021 at Beijing Hospital were evaluated retrospectively. A total of 209 lesions from 184 patients were finally included. All patients were female, aged (50±11) years (range: 27 to 76 years). All lesions were confirmed by pathology and divided into malignancy and non-malignancy. The lesions were divided into mass and non-mass type using BI-RADS. The receiver operator characteristic (ROC) curve was used to evaluate the diagnostic performance of the new scoring system. Four types of pathology-obtaining pathway were used: biopsy guided by second-look ultrasound, local excision guided by lesion position information on MRI, intraductal lesion excision guided by methylene blue stain and mastectomy. The data between mass and non-mass lesions were compared by Mann-Whitney U test, χ2 test or Fisher exact test,respectively. Results: There were 124 malignant and 85 non-malignant lesions, while 100 mass and 109 non-mass lessions. The sizes between mass and non-mass lesions showed significant difference(M(IQR)) (7.0 (3.0) mm vs. 25.0 (25.0) mm, U=568.000, P<0.01) and their BI-RADS diagnostic accuracy had no significant difference (53.0% (53/100) vs. 65.1% (71/109), χ2=3.184, P=0.074). The areas under ROC curve of the new scoring system for evaluating mass and non-mass were 0.841 and 0.802, respectively. When taking Score 3 as threshold, it can potentially avoid 14.0% (14/100) and 4.6% (5/109) of biopsies in mass and non-mass, respectively. As to pathway of obtaining pathology, second-look ultrasound succeeded more easily in mass than non-mass (41.0% (41/100) vs.26.6% (29/109), χ2=4.851, P=0.028). More MRI-guided local excisions were performed in non-mass than mass (52.3% (57/109) vs. 34.0% (34/100), χ2=7.100, P=0.008). Conclusions: For suspicious breast lesions detected by MRI but not suspected on X-ray or ultrasound, the new scoring system can further increase diagnostic accuracy. The second-look ultrasound plays an important role for obtaining pathology, especially for mass-type lesion.


Asunto(s)
Humanos , Femenino , Masculino , Estudios Retrospectivos , Neoplasias de la Mama/diagnóstico por imagen , Mastectomía , Radiografía , Imagen por Resonancia Magnética
7.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1019815

RESUMEN

Objective To observe the expression of tyrosine kinase 2(JAK2)and signal transducer and activator of transcription 3(STAT3)in myocardial tissue of rats with myocardial ischemia-reperfusion injury(MIRI)by electroacupuncture at"Neiguan"point,and explore the mechanism of electroacupuncture in up regulating JAK2/STAT3 signal pathway,promoting the expression of anti-inflammatory factors,and reducing MIRI injury.Methods Thirty male SD rats with normal echocardiography were randomly divided into sham operation group,model group and electroacupuncture group,with 10 rats in each group.MIRI models were prepared by ligation of left anterior descending coronary artery(LAD)in model group and electroacupuncture group,while in sham operation group,only threading was performed without ligation.In the electroacupuncture group,electroacupuncture(density wave,2 Hz/100 Hz,2 mA)at bilateral"Neiguan"points was performed on the 1st,3rd and 5th days after the modeling operation,once a day,20 minutes each time.The left ventricular ejection fraction(LVEF)of rats on the 1st,3rd and 5th day after operation was observed by echocardiography to evaluate cardiac function;HE staining was used to observe the pathological changes of rat myocardium;The myocardial fibrosis was observed by Masson staining;The expression of IL-4 and IL-6 in myocardium was detected by ELISA;The expressions of IL-1β and IL-10 in myocardial tissue were detected by immunohistochemistry;The expression of JAK2,p-JAK2,STAT3,p-STAT3 protein in myocardial infarction area was measured by Western blot.Results Compared with sham operation group,EF in model group decreased significantly(P<0.05),fibrosis area increased(P<0.05),IL-4,IL-6,IL-10,IL-1β The content of JAK2,p-JAK2,STAT3,p-STAT3 protein increased(P<0.05);Compared with the model group,the EF of rats in the electroacupuncture group increased(P<0.05),the fibrotic area of rats in the electroacupuncture group decreased(P<0.05),the content of IL-4 and IL-10 increased,and IL-6 and IL-1β The expression of JAK2,p-JAK2,STAT3,p-STAT3 protein increased(P<0.05).Conclusion Electroacupuncture at Neiguan point can significantly up regulate JAK2/STAT3 signal pathway,reduce the secretion of proinflammatory factors,increase the expression of anti-inflammatory factors,and alleviate myocardial ischemia reperfusion injury in rats.

8.
BMC Cancer ; 22(1): 1222, 2022 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-36443693

RESUMEN

INTRODUCTION: Clinicians increasingly perform laparoscopic surgery for intrahepatic cholangiocarcinoma (ICC). However, this surgery can be difficult in patients with advanced-stage ICC because of the complicated procedures and difficulty in achieving high-quality results. We compared the effects of a three-step optimized procedure with a traditional procedure for patients with advanced-stage ICC. METHODS: Forty-two patients with advanced-stage ICC who received optimized laparoscopic hemihepatectomy with lymph node dissection (LND, optimized group) and 84 propensity score-matched patients who received traditional laparoscopic hemihepatectomy plus LND (traditional group) were analyzed. Surgical quality, disease-free survival (DFS), and overall survival (OS) were compared. RESULTS: The optimized group had a lower surgical bleeding score (P = 0.038) and a higher surgeon satisfaction score (P = 0.001). Blood loss during hepatectomy was less in the optimized group (190 vs. 295 mL, P < 0.001). The optimized group had more harvested LNs (12.0 vs. 8.0, P < 0.001) and more positive LNs (8.0 vs. 5.0, P < 0.001), and a similar rate of adequate LND (88.1% vs. 77.4%, P = 0.149). The optimized group had longer median DFS (9.0 vs. 7.0 months, P = 0.018) and median OS (15.0 vs. 13.0 months, P = 0.046). In addition, the optimized group also had a shorter total operation time (P = 0.001), shorter liver resection time (P = 0.001), shorter LND time (P < 0.001), shorter hospital stay (P < 0.001), and lower incidence of total morbidities (14.3% vs. 36.9%, P = 0.009). CONCLUSIONS: Our optimization of a three-step laparoscopic procedure for advanced ICC was feasible, improved the quality of liver resection and LND, prolonged survival, and led to better intraoperative and postoperative outcomes.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Laparoscopía , Humanos , Laparoscopía/efectos adversos , Colangiocarcinoma/cirugía , Hepatectomía/efectos adversos , Neoplasias de los Conductos Biliares/cirugía , Conductos Biliares Intrahepáticos
9.
J Plant Physiol ; 273: 153697, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35487008

RESUMEN

Alternaria blotch disease, caused by Alternaria alternata apple pathotype (AAAP), is one of the most prevalent diseases in apple production. To identify AAAP resistance-related genes and provide a theoretical basis for Alternaria blotch disease resistance breeding, we used two apple cultivars, 'Jonathan', a variety resistant to AAAP infection, and 'Starking Delicious', a variety susceptible to AAAP infection, as materials to perform transcriptome sequencing of apple leaves 72 h after AAAP infection. A Venn diagram showed that a total of 5229 DEGs of 'Jonathan' and 4326 DEGs of 'Starking Delicious' were identified. GO analysis showed that these DEGs were clustered into 25 GO terms, primarily "metabolic process" and "catalytic activity." Functional classification analyses of the DEGs indicated that "MAPK signaling pathway-plant pathway" is the most significant metabolic pathway among the top 15 KEGG pathways, followed by the "plant hormone signal transduction" pathway. There are more DEGs in 'Jonathan' that are significantly classified GO terms and KEGG pathways than in 'Starking Delicious'. Specifically, 13 DEGs were identified as involved in the GA-GID1-DELLA module, and the expression of MdGRAS53, a homologous gene of DELLA, was significantly upregulated in 'Jonathan' compared with 'Starking Delicious'. Phenotype analysis revealed that exogenous hormone GA3 suppressed apple resistance to AAAP infection and reduced the expression of MdGRAS53. The opposite result was observed for exogenous spraying of paclobutrazol (PAC), an inhibitor of gibberellin synthesis. Overexpression of MdGRAS53 in apple leaves by transient transformation decreased lesion area and the number of spores in leaves infected with AAAP, while silencing MdGRAS53 showed the opposite result. Meanwhile, SA/JA signaling pathway-related genes were upregulated significantly in MdGRAS53-overexpressed leaves and downregulated significantly in MdGRAS53-silenced leaves. The findings suggest that the GA-GID1-DELLA module is involved in apple resistance to AAAP, and MdGRAS53, a DELLA homologous gene, may play a positive role in this resistance by modulating cooperative JA- and SA-dependent pathways.


Asunto(s)
Resistencia a la Enfermedad , Malus , Alternaria , Resistencia a la Enfermedad/genética , Regulación de la Expresión Génica de las Plantas , Malus/genética , Malus/metabolismo , Fitomejoramiento , Enfermedades de las Plantas/genética , Transcriptoma
10.
Plant Cell Environ ; 45(5): 1520-1536, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35150141

RESUMEN

Nitrogen (N) is an essential macronutrient for crop growth and yield. Improving the N use efficiency (NUE) of crops is important to agriculture. However, the molecular mechanisms underlying NUE regulation remain largely elusive. Here we report that the OsNLP3 (NIN-like protein 3) regulates NUE and grain yield in rice under N sufficient conditions. OsNLP3 transcript level is significantly induced by N starvation and its protein nucleocytosolic shuttling is specifically regulated by nitrate. Loss-of-function of OsNLP3 reduces plant growth, grain yield, and NUE under sufficient nitrate conditions, whereas under low nitrate or different ammonium conditions, osnlp3 mutants show no clear difference from the wild type. Importantly, under sufficient N conditions in the field, OsNLP3 overexpression lines display improved grain yield and NUE compared with the wild type. OsNLP3 orchestrates the expression of multiple N uptake and assimilation genes by directly binding to the nitrate-responsive cis-elements in their promoters. Overall, our study demonstrates that OsNLP3, together with OsNLP1 and OsNLP4, plays overlapping and differential roles in N acquisition and NUE, and modulates NUE and the grain yield increase promoted by N fertilizer. Therefore, OsNLP3 is a promising candidate gene for the genetic improvement of grain yield and NUE in rice.


Asunto(s)
Oryza , Grano Comestible/metabolismo , Fertilizantes , Nitratos/metabolismo , Nitrógeno/metabolismo , Oryza/genética , Oryza/metabolismo
11.
Acta Pharmacol Sin ; 42(5): 744-754, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-32753731

RESUMEN

Currently, dendritic cell-specific transmembrane protein (DC-STAMP), a multipass transmembrane protein, is considered as the master regulator of cell-cell fusion, which underlies the formation of functional multinucleated osteoclasts. Thus, DC-STAMP has become a promising target for osteoclast-associated osteolytic diseases. In this study, we investigated the effects of oridonin (ORI), a natural tetracyclic diterpenoid compound isolated from the traditional Chinese herb Rabdosia  rubescens, on osteoclastogenesis in vivo and ex vivo. ICR mice were injected with LPS (5 mg/kg, ip, on day 0 and day 4) to induce inflammatory bone destruction. Administration of ORI (2, 10 mg·kg-1·d-1, ig, for 8 days) dose dependently ameliorated inflammatory bone destruction and dramatically decreased DC-STAMP protein expression in BMMs isolated from LPS-treated mice. Treatment of preosteoclast RAW264.7 cells with ORI (0.78-3.125 µM) dose dependently inhibited both mRNA and protein levels of DC-STAMP, and suppressed the following activation of NFATc1 during osteoclastogenesis. Knockdown of DC-STAMP in RAW264.7 cells abolished the inhibitory effects of ORI on RANKL-induced NFATc1 activity and osteoclast formation. In conclusion, we show for the first time that ORI effectively attenuates inflammation-induced bone loss by suppressing DC-STAMP expression, suggesting that ORI is a potential agent against inflammatory bone diseases.


Asunto(s)
Conservadores de la Densidad Ósea/uso terapéutico , Diterpenos de Tipo Kaurano/uso terapéutico , Proteínas de la Membrana/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Osteólisis/tratamiento farmacológico , Animales , Regulación hacia Abajo/efectos de los fármacos , Femenino , Lipopolisacáridos , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Factores de Transcripción NFATC/metabolismo , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteogénesis/efectos de los fármacos , Osteólisis/inducido químicamente , Osteólisis/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Células RAW 264.7 , Transducción de Señal/efectos de los fármacos
12.
Dig Dis Sci ; 66(4): 1063-1071, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-32462510

RESUMEN

BACKGROUND: Interferon regulatory factor 9 (IRF9) acts as a negative regulator of sirtuin-1 (SIRT1) to participate in many diseases. However, the role of SIRT1 and IRF9 in hyperlipidemia acute pancreatitis associated with kidney injury is unclear. AIMS: To explore the function of SIRT1 and IRF9 in hyperlipidemia acute pancreatitis associated with kidney injury and provide theoretical guidance for disease diagnosis and treatment. METHODS: Model rats were established by intraperitoneal injection of 20% L-arginine. Apoptosis of kidney tissue was determined by TUNEL staining. Expressions of IRF9, SIRT1, p53, and acetylated p53 were detected by qRT-PCR and Western blot. Dual-Luciferase Reporter Assay was carried out to validate the regulation of IRF9 on SIRT1. RESULTS: Pancreatic and renal injury was more serious, and apoptosis of kidney epithelial cells increased in acute pancreatitis (AP) and hyperlipidemia acute pancreatitis (HLAP) group. IRF9, p53, and acetylated p53 were up-regulated, and SIRT1 was down-regulated in AP and HLAP group (p < 0.05). Down-regulation of SIRT1 was negatively correlated with up-regulation of IRF9 in AP and HLAP group (p < 0.05). Pancreatic and renal injury and kidney epithelial cells apoptosis in HLAP group were more obvious than AP group (p < 0.05). The up-regulation of IRF9 and down-regulation of SIRT1 in HLAP group were more than AP group (p < 0.05). The promoter activity of SIRT1 was repressed by IRF9. CONCLUSION: In pancreatitis associated with kidney injury, IRF9 was a negative regulator of SIRT1, down-regulated the expression of SIRT1, increased acetylated p53, and promoted renal cell apoptosis. Hyperlipidemia further aggravated pancreatic and renal injury and renal cell apoptosis.


Asunto(s)
Hiperlipidemias , Subunidad gamma del Factor 3 de Genes Estimulados por el Interferón/metabolismo , Enfermedades Renales , Pancreatitis , Sirtuina 1/metabolismo , Animales , Apoptosis , Proteínas Reguladoras de la Apoptosis/metabolismo , Regulación hacia Abajo , Regulación de la Expresión Génica , Hiperlipidemias/complicaciones , Hiperlipidemias/metabolismo , Enfermedades Renales/complicaciones , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Pancreatitis/etiología , Pancreatitis/metabolismo , Ratas , Índice de Severidad de la Enfermedad , Transducción de Señal , Proteína p53 Supresora de Tumor/metabolismo
13.
Mol Cell Biochem ; 472(1-2): 125-134, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32577948

RESUMEN

Acute pancreatitis (AP) is an inflammatory disease caused by the abnormal activation of pancreatic enzymes in the pancreas, with a considerably high morbidity and mortality. However, the etiological factor and pathogenesis of AP are still unclear. This study was aimed to explore the role and mechanism of interferon regulatory factor 9 (IRF9) in the occurrence of AP and to provide experimental and theoretical foundation for AP diagnosis and treatment. AP model in vitro was established by caerulein-induced group. Small interfering RNA (siRNA) was designed and constructed to silence IRF9 gene. After siRNA transfected and caerulein treated successfully, the expression levels of IRF9, SIRT1, and acetylated p53 (Ac-p53) were determined by qRT-PCR and Western blot. The apoptosis, proliferation, and migration of AR42J cells were checked by flow cytometry, MTT, and transwell assay. Dual-luciferase reporter assay was implemented to validate the regulatory effect of IRF9 on SIRT1. Here, our study showed that the expression of IRF9 and Ac-p53 was increased, SIRT1 was decreased, and cell apoptosis, proliferation, and migration of AR42J cells were increased after caerulein induced. IRF9 gene silencing upregulated SIRT1, downregulated Ac-p53, and inhibited cell apoptosis, proliferation, and migration. Dual-Luciferase reporter assay showed that IRF9 could negatively regulate SIRT1. The potential mechanism was that IRF9 could modulate cell apoptosis, proliferation, migration, and bind the promoter of SIRT1 to repress SIRT1-p53. It hinted that IRF9 showed a novel function in AP by modulating cell apoptosis, proliferation, migration, and suppressing SIRT1-p53. IRF9 might be a good potential treatment target for AP.


Asunto(s)
Apoptosis , Movimiento Celular , Proliferación Celular , Subunidad gamma del Factor 3 de Genes Estimulados por el Interferón/metabolismo , Pancreatitis/patología , Sirtuina 1/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Animales , Biomarcadores/metabolismo , Células Cultivadas , Regulación de la Expresión Génica , Subunidad gamma del Factor 3 de Genes Estimulados por el Interferón/genética , Pancreatitis/genética , Pancreatitis/metabolismo , Ratas , Sirtuina 1/genética , Proteína p53 Supresora de Tumor/genética
14.
Acta Pharmacol Sin ; 41(2): 229-236, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31431733

RESUMEN

In chronic infectious diseases caused by gram-negative bacteria, such as osteomyelitis, septic arthritis, and periodontitis, osteoclastic activity is enhanced with elevated inflammation, which disturbs the bone homeostasis and results in osteolysis. Lipopolysaccharide (LPS), as a bacteria product, plays an important role in this process. Recent evidence shows that an antimalarial drug artesunate attenuates LPS-induced osteolysis independent of RANKL. In this study we evaluated the effects of artesunate on LPS-induced osteoclastogenesis in vitro and femur osteolysis in vivo, and explored the mechanisms underlying the effects of artesunate on LPS-induced osteoclast differentiation independent of RANKL. In preosteoclastic RAW264.7 cells, we found that artesunate (1.56-12.5 µM) dose dependently inhibited LPS-induced osteoclast formation accompanied by suppressing LPS-stimulated osteoclast-related gene expression (Fra-2, TRAP, Cathepsin K, ß3-integrin, DC-STAMP, and Atp6v0d2). We showed that artesunate (3.125-12.5 µM) inhibited LPS-stimulated nuclear factor of activated T cells c1 (NFATc1) but not NF-κB transcriptional activity; artesunate (6.25, 12.5 µM) significantly inhibited LPS-stimulated NFATc1 protein expression. Furthermore, artesunate treatment markedly suppressed LPS-induced Ca2+ influx, and decreased the expression of PP2B-Aα (calcineurin) and pPLCγ1 in the cells. In addition, artesunate treatment significantly decreased the expression of upstream signals TLR4 and TRAF6 during LPS-induced osteoclastogenesis. Administration of artesunate (10 mg/kg, ip) for 8 days effectively inhibited serum TNF-α levels and ameliorated LPS (5 mg/kg, ip)-induced inflammatory bone loss in vivo. Taken together, artesunate attenuates LPS-induced inflammatory osteoclastogenesis by inhibiting the expression of TLR4/TRAF6 and the downstream PLCγ1-Ca2+-NFATc1 signaling pathway. Artesunate is a valuable choice to treat bone loss induced by gram-negative bacteria infection or inflammation in RANKL-independent pathway.


Asunto(s)
Antimaláricos/farmacología , Artesunato/farmacología , Inflamación/tratamiento farmacológico , Osteoclastos/efectos de los fármacos , Animales , Antimaláricos/administración & dosificación , Artesunato/administración & dosificación , Calcio/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Inflamación/patología , Lipopolisacáridos , Ratones , Ratones Endogámicos ICR , Factores de Transcripción NFATC/metabolismo , Osteoclastos/citología , Osteogénesis/efectos de los fármacos , Fosfolipasa C gamma/metabolismo , Células RAW 264.7 , Transducción de Señal/efectos de los fármacos , Factor 6 Asociado a Receptor de TNF/metabolismo , Receptor Toll-Like 4/metabolismo
15.
Huan Jing Ke Xue ; 40(7): 3030-3038, 2019 Jul 08.
Artículo en Chino | MEDLINE | ID: mdl-31854700

RESUMEN

Studying the isotope characteristics and water body transformation relationships among different water bodies in the hilly and gully region of the Loess Plateau can provide a theoretical foundation for evaluating regional climate, ecology, and water resources. In this study, daily and monthly averaged δD and δ18O in precipitation, river water, and shallow groundwater were measured in 2017 in the Jiuyuangou watershed, which has a good ecological condition. The compositional relationship between the stable hydrogen and oxygen isotopes in difference water bodies was explored, the influence factors and spatio-temporal variation of δ18O in precipitation and river water were analyzed, and the stable isotope conversion ratios between different water bodies in the study area were calculated using the two-terminal mixed model. The main conclusions of the study are as follows:the d-excess of river water showed an increasing trend with elevation during the observation period; the δ18O of river water was enriched with increasing distance from the river source and decreased with increasing altitude; temperature, wind speed, and relative humidity had significant effects on the hydrogen and oxygen isotopes of precipitation; precipitation and shallow groundwater replenish the river during the non-flood period, the proportions of which were 46% and 54%, respectively; and during the flood season, the shallow groundwater is replenished by river water and precipitation, the proportions were 60% and 40%, respectively. These results indicate that there is a good conversion relationship between "precipitation-river-shallow groundwater" in the study area. The implementation of soil and water conservation measures has had some influence on the conversion of different water bodies in small watersheds. The results provide a basis for the establishment of water cycle models for hilly and gully regions of the Loess Plateau.

16.
Artículo en Inglés | MEDLINE | ID: mdl-31871480

RESUMEN

OBJECTIVE: The aim of this study was to evaluate the effectiveness of traditional Chinese medicine- (TCM-) guided dietary interventions in improving yang-qi deficiency and yin-blood deficiency TCM syndromes according to the principles of TCM syndrome differentiation theory in male youths undergoing drug detoxification during the rehabilitation period who stayed in a compulsory isolation detoxification center. METHODS: Male youths undergoing drug detoxification who met the criteria to be included in the study were randomly divided into the intervention group (n = 62) and the control group (n = 61) according to a random number table in a 1 : 1 ratio. The intervention group received a TCM-guided diet, and the control group received routine food support. Over an intervention period of 3 months, we observed changes in the TCM syndrome element scores in the two groups before and after intervention. RESULTS: After 3 months, the qi deficiency, yin deficiency, blood deficiency, and yin-blood deficiency syndrome in the intervention group improved significantly (P values 0.009, 0.000, 0.005, and 0.001, respectively). In the control group, yang deficiency, qi deficiency, and yang-qi deficiency syndromes worsened significantly (P values 0.003, 0.032, and 0.009, respectively). The differences (post-pre) in yang deficiency, qi deficiency, yang-qi deficiency, yin deficiency, blood deficiency, and yin-blood deficiency syndromes between the two groups were statistically significant (P values 0.003, 0.003, 0.003, 0.001, 0.005, and 0.002, respectively). CONCLUSION: A TCM-guided diet can delay the worsening of yang-qi deficiency syndrome symptoms and improve yin-blood deficiency syndrome and the prognosis of male youth undergoing drug detoxification during the rehabilitation period.

17.
Clin Lab ; 65(8)2019 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-31414744

RESUMEN

BACKGROUND: Recently, long non-coding RNAs (lncRNAs) have attracted substantial attention owing to their unforeseen critical roles in a wide range of biological processes. The aim of our study was to provide an overview of lncRNA expression profiles in plasma of RA patients. METHODS: The Agilent LncRNA + mRNA Human Gene Expression Microarray V4.0 was employed to determine differentially expressed (DE) lncRNAs and mRNAs in plasma of four female newly diagnosed and DMARD-naïve RA patients and four female age-matched healthy controls. The KOBAS (KEGG Orthology Based Annotation System) software was applied to determine the gene ontology (GO) terms and pathway in which the DE mRNAs were enriched. Furthermore, a lncRNA-mRNA co-expression network was constructed according to the correlation between DE lncRNAs and mRNAs. RESULTS: Compared with healthy controls, a total of 289 DE lncRNAs (169 up-regulated and 120 down-regulated) and 468 DE mRNAs (280 up-regulated and 188 down-regulated) were found in the plasma of patients with RA. Bioinformatics analysis indicated that the DE mRNAs might be involved in the pathogenesis of RA mainly through platelets. In addition, a co-expression network composed of 229 network nodes and 340 connections between 116 lncRNAs and 113 mRNAs was constructed. CONCLUSIONS: We characterized the plasma lncRNA expression profiles in RA patients for the first time. Our results could shed new light on the pathogenesis of RA and help identify lncRNAs as novel diagnostic biomarkers and therapeutic targets for RA.


Asunto(s)
Artritis Reumatoide/genética , Biomarcadores/metabolismo , Perfilación de la Expresión Génica/métodos , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , ARN Largo no Codificante/genética , Adulto , Artritis Reumatoide/sangre , Artritis Reumatoide/diagnóstico , Biomarcadores/sangre , Biología Computacional , Femenino , Ontología de Genes , Redes Reguladoras de Genes/genética , Humanos , Persona de Mediana Edad , ARN Largo no Codificante/sangre , ARN Mensajero/sangre , ARN Mensajero/genética , Transducción de Señal/genética
18.
J Clin Lab Anal ; 33(5): e22862, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30779461

RESUMEN

BACKGROUND: Emerging evidence indicates that some hematological markers have critical value in evaluating treatment response. This study was performed to determine the clinical value of hemoglobin (Hb), platelet (Plt), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in rheumatoid arthritis (RA) patients treated with tocilizumab (TCZ). METHODS: Fifty-two RA patients receiving TCZ were recruited and followed for 6 months. The values of abovementioned hematological markers were collected. Clinical disease activity index (CDAI) and disease activity score based on 28 joints (DAS28)-ESR were calculated. Correlation analysis was conducted by calculating Pearson's correlation coefficient. The change in disease activity between groups according to the baseline level of hematological markers was compared by t test. RESULTS: Significant correlation between change in NLR (△NLR), change in PLR (△PLR), and change in CDAI (△CDAI) was found (△NLR: r = 0.30, P = 0.03; △PLR: r = 0.31, P = 0.03). The change in Plt (△Plt) was correlated with change in DAS28-ESR (△DAS28-ESR) (r = 0.36, P = 8.24 × 10-3 ). Greater improvement in CDAI was seen in patients categorized into Plt high group (t = 2.06, P = 0.04), NLR high group (t = 2.15, P = 0.04), and PLR high group (t = 2.41, P = 0.02) compared with the contrast group. CONCLUSION: Our study demonstrated that △Plt, △NLR, and △PLR could be used to monitor the clinical response to TCZ. RA patients with high baseline levels of Plt, NLR, and PLR achieved more improvement, indicating these hematological markers might be utilized to guide TCZ treatment.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Artritis Reumatoide/sangre , Artritis Reumatoide/tratamiento farmacológico , Biomarcadores/sangre , Adulto , Artritis Reumatoide/etiología , Femenino , Hemoglobinas/análisis , Humanos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Neutrófilos/efectos de los fármacos , Recuento de Plaquetas , Estudios Prospectivos , Resultado del Tratamiento
19.
Fitoterapia ; 133: 159-170, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30654127

RESUMEN

Eleven undescribed ent-kauranes, named agallochanins A-K, were isolated from the stems and twigs of the Chinese semi-mangrove plant, Excoecaria agallocha L.. The absolute configurations of these diterpenoid compounds, except for the chirality of C-4 in agallochanin H, were unequivocally determined by HR-ESIMS, extensive NMR investigations, single-crystal X-ray diffraction analyses with Cu Kα radiation, quantum-chemical electronic circular dichroism (ECD) calculations, the comparison of experimental ECD spectra, and the modified Mosher's α-methoxy-α-(trifluoromethyl)phenylacetyl (MTPA) ester method. Agallochanins A-I are 3,4-seco-ent-kauranes. Agallochanin D represents the first example of 3,4-seco-17-nor-ent-kaurane. Agallochanin K exhibited NF-κB inhibitory activity with the inhibition rate of 79.6% at the concentration of 100.0 µM.


Asunto(s)
Diterpenos de Tipo Kaurano/farmacología , Euphorbiaceae/química , FN-kappa B/antagonistas & inhibidores , Animales , Línea Celular Tumoral , Diterpenos de Tipo Kaurano/aislamiento & purificación , Humanos , Ratones , Estructura Molecular , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Células RAW 264.7
20.
Arch Rheumatol ; 34(4): 406-413, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32010889

RESUMEN

OBJECTIVES: This study aims to determine whether baseline body mass index (BMI) affects clinical response to tocilizumab (TCZ) after six months of treatment in rheumatoid arthritis (RA) patients. PATIENTS AND METHODS: In this prospective study, a total of 52 RA patients (10 males, 42 females; mean age 50.6±12.2 years; range, 23 to 73 years) receiving intravenous TCZ were consecutively recruited and followed-up for six months. BMI was calculated before initiation of TCZ treatment. The primary clinical response criterion was clinical disease activity index (CDAI) low disease activity (LDA) and the secondary clinical response criteria included CDAI remission, disease activity score based on 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) LDA, DAS28-ESR remission, European League Against Rheumatism (EULAR) good response, and decreased DAS28-ESR (ΔDAS28-ESR)≥1.2. RESULTS: The number of RA patients classified as normal weight, overweight, and obese according to baseline BMI was 38 (73.1%), eight (15.4%), and six (11.5%), respectively. Similar baseline BMI median levels were found between RA patients reaching CDAI LDA and non-LDA: 21.11 (18.94-23.72) versus 20.78 (20.03-22.29) (p=0.98), and non-significant difference in the proportion of responders between normal weight and overweight/obese RA patients was found (p=0.47). No significant difference was found when the secondary clinical response criteria were applied. CONCLUSION: Our study demonstrates that BMI is not associated with clinical response to TCZ among RA patients and TCZ may be used to treat RA patients regardless of BMI levels.

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