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1.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(8): 814-820, 2021 Aug 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34511171

RESUMO

OBJECTIVES: To study the survival rate and the incidence of complications of very preterm infants and the factors influencing the survival rate and the incidence of complications. METHODS: The medical data of the very preterm infants with a gestational age of <32 weeks and who were admitted to the Department of Neonatology in 11 hospitals of Jiangsu Province in China from January 2018 to December 2019 were retrospectively reviewed. Their survival rate and the incidence of serious complications were analyzed. A multivariate logistic regression analysis was used to evaluate the risk factors for death and serious complications in very preterm infants. RESULTS: A total of 2 339 very preterm infants were enrolled, among whom 2 010 (85.93%) survived and 1 507 (64.43%) survived without serious complications. The groups with a gestational age of 22-25+6 weeks, 26-26+6 weeks, 27-27+6 weeks, 28-28+6 weeks, 29-29+6 weeks, 30-30+6 weeks, and 31-31+6 weeks had a survival rate of 32.5%, 60.6%, 68.0%, 82.9%, 90.1%, 92.3%, and 94.8% respectively. The survival rate tended to increase with the gestational age (P<0.05) and the survival rate without serious complications in each gestational age group was 7.5%, 18.1%, 34.5%, 52.2%, 66.7%, 75.7%, and 81.8% respectively, suggesting that the survival rate without serious complications increased with the gestational age (P<0.05). The multivariate logistic regression analysis showed that high gestational age, high birth weight, and prenatal use of glucocorticoids were protective factors against death in very preterm infants (P<0.05), and 1-minute Apgar score ≤3 was a risk factor for death in very preterm infants (P<0.05); high gestational age and high birth weight were protective factors against serious complications in very preterm infants who survived (P<0.05), while 5-minute Apgar score ≤3 and maternal chorioamnionitis were risk factors for serious complications in very preterm infants who survived (P<0.05). CONCLUSIONS: The survival rate is closely associated with gestational age in very preterm infants. A low 1-minute Apgar score (≤3) may increase the risk of death in very preterm infants, while high gestational age, high birth weight, and prenatal use of glucocorticoids are associated with the reduced risk of death. A low 5-minute Apgar score (≤3) and maternal chorioamnionitis may increase the risk of serious complications in these infants, while high gestational age and high birth weight may reduce the risk of serious complications.


Assuntos
Doenças do Prematuro , Recém-Nascido Prematuro , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Gravidez , Estudos Retrospectivos , Taxa de Sobrevida
2.
Seizure ; 92: 189-194, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34551365

RESUMO

PURPOSE: This study aimed to investigate the incidence and predictors of epilepsy after anti-neuronal antibody-positive autoimmune encephalitis (AIE). The clinical outcomes of patients with epilepsy after AIE were also explored. METHODS: A total of 111 AIE patients were retrospectively evaluated. Post-AIE epilepsy (PAEE) was defined as at least one unprovoked seizure occurring six or more months after discharge from hospital. RESULTS: The incidence of acute symptomatic seizures was 80.2% (89/111) in our AIE patients. Furthermore, of the 89 AIE patients with seizures, 29 (32.6%) presented with seizures as the initial symptom. Overall, 44 out of 111 AIE patients (39.6%) had unprovoked seizures after six months, meeting our definition of PAEE. The independent risk factors for PAEE incidence included an initial presentation with new-onset refractory status epilepticus (NORSE), delayed immunotherapy treatment, the complication of a lung infection during admission, the requirement for mechanical ventilation during hospitalization, parietal lesions observed in magnetic resonance imaging (MRI), and focal slow waves on electroencephalographic (EEG) monitoring. CONCLUSIONS: Early initiation of immunotherapy and lung infection treatment may reduce the risk of conversion of symptomatic seizures to chronic epilepsy in the acute phase of AIE. In general, PAEE patients could have a good prognosis if treated properly and in a timely fashion.

3.
J Ethnopharmacol ; 281: 114542, 2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34428525

RESUMO

ETHNOPHARMACOLOGY RELEVANCE: The root bark of Morus alba Linn. (M. alba), a traditional folk medicine, has been documented in the Chinese Pharmacopoeia, which has been widely used for asthma, fever, pneumonia, edema, vomit, colitis, bronchitis and keratitis diseases. Some of the diseases may be related to respiratory, digestive, urinary tract infections. Although Diels-Alder adducts (DAAs), flavonoids, 2-arylbenzofurans and stilbene compounds have been isolated from the root bark of M. alba, few compounds are reported for their antimicrobial efficacy in vivo and the mechanism. AIM OF THE STUDY: The aim of the study was to isolate and identify compounds of the root bark of M. alba in view of their anti-MRSA bioactivity, evaluate the anti-MRSA bioactivity of compounds and 60% ethanol elution (MA-6) in vitro and in vivo, and explore preliminary antibacterial mechanism in order to provide natural resources against MRSA infection. MATERIALS AND METHODS: Systematic phytochemical investigations were carried out according to the thin layer chromatography (TLC) of the active fraction MA-6 to find more anti-MRSA ingredients. The compounds of the root bark of M. alba were separated by column chromatography and identified by LC-MS/MS and NMR spectroscopy. The anti-MRSA efficacy of the active ingredients were evaluated by broth microdilution method and a murine infection model. The mode of action of compounds was explored by time-kill curve and post-contact effect. The preliminary mechanism of compounds against MRSA was explored by drug efflux pumps and bacterial biofilms. RESULTS: Chemical isolation resulted in twenty-nine known compounds, most with one or more geranyl and prenyl units exhibited superior anti-MRSA bioactivity, with MIC values of 2-16 µg/mL. In addition, the mode of action indicated that compounds presented persistent antimicrobial effect, which also produced concentration-dependent and time-dependent killing activity or property. Preliminary mechanism showed that the compound kuwanon O (29) damaged the bacterial cell membranes, leading to the accumulation of antibiotics inside bacterial cells, moreover, MA-6 and kuwanon O (29) inhibited the efflux of drugs by combining with methicillin or ethidium bromide (EtBr), resulting in the MICs of EtBr and methicillin were obviously decreased three-fold. The anti-MRSA efficacy in vivo indicated that the active fraction MA-6 could reduce bacteria in spleen, liver, kidney and mortality of acutely infectious mice, which was better than the positive drug berberine chloride. CONCLUSION: Experimental investigation showed that the MA-6 and compound 29 have promising bioactivity against MRSA in vitro and in vivo, which might be used as a potential source of new antibacterial medicine or a potential efflux pump inhibitor against MRSA infection.

4.
Zhongguo Zhong Yao Za Zhi ; 46(14): 3687-3693, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34402293

RESUMO

A LC-MS/MS method was developed for the rapid and simultaneous determination of genipin-1-ß-D-gentiobioside,geniposide,naringin,hesperidin and neohesperidin in SD rat plasma.The linear relationships of these five constituents in rats were validated,and the specificity,accuracy,precision and stability met the requirements.Their pharmacokinetic parameters were calculated by DAS 3.2.2,and the results showed that the metabolic process in vivo of the five constituents accorded with the characteristics of noncompartmental model.Their main pharmacokinetic parameters were listed as follows:(1) genipin-1-ß-D-gentiobioside:t_(1/2)(3.20±0.51)h,C_(max)(403.15±96.93)µg·L~(-1)and AUC_(0-t)(612.56±148.50)µg·L~(-1)·h for the model group,while t_(1/2)(3.07±0.75) h,C_(max)(229.50±60.63)µg·L~(-1)and AUC_(0-t)(413.14±76.37)µg·L~(-1)·h for the normal group;(2) geniposide:t_(1/2)(3.24±0.68) h,C_(max)(2 961.40±688.02)µg·L~(-1),and AUC_(0-t)(10 972.87±1 992.96)µg·L~(-1)·h for the model group,while t_(1/2)(4.56±0.96) h,C_(max)(1 833.27±558.13)µg·L~(-1),and AUC_(0-t)(8 996.27±3 053.48)µg·L~(-1)·h for the normal group;(3) naringin:t_(1/2)(1.64±0.59) h,C_(max)(415.13±259.54)µg·L~(-1),and AUC_(0-t)(608.62±289.05)µg·L~(-1)·h for the model group,while t_(1/2)(1.02±0.25) h,C_(max)(355.08±180.00)µg·L~(-1),and AUC_(0-t)(501.07±242.68)µg·L~(-1)·h for the normal group;(4) hesperidin:t_(1/2)(0.86±0.29) h,C_(max)(95.17±22.80)µg·L~(-1)and AUC_(0-t)(141.19±54.63)µg·L~(-1)·h for the model group,while t_(1/2)(0.95±0.31) h,C_(max)(46.48±18.33)µg·L~(-1)and AUC_(0-t)(69.51±14.73)µg·L~(-1)·h for the normal group;(5) neohesperidin:t_(1/2)(0.89±0.29) h,C_(max)(828.78±361.56)µg·L~(-1)and AUC_(0-t)(1 292.29±553.73)µg·L~(-1)·h for the model group,while t_(1/2)(0.90±0.31) h,C_(max)(314.68±172.45)µg·L~(-1)and AUC_(0-t)(385.99±138.55)µg·L~(-1)·h for the normal group.


Assuntos
Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Ratos , Ratos Sprague-Dawley
5.
BMC Psychiatry ; 21(1): 326, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34210279

RESUMO

BACKGROUND: Although childhood abuse is considered to be related to borderline personality disorder (BPD), few studies have elaborated on the mediating role of self-esteem and resilience in it. Thus, the present study aimed to explore the potential mediating role of resilience and self-esteem between childhood abuse and BPD. METHODS: This cross-sectional study was conducted with 4034 college students in Anhui Province, China. Participants were asked to complete Chinese versions of the following instruments: Childhood Trauma Questionnaire-Short Form (CTQ-SF), Mclean Screening Instrument for Borderline Personality Disorder (MSI-BPD), Connor-Davidson Resilience Scale (CD-RISC), and Rosenberg Self-Esteem Scale (RSES). Structural equation modeling (SEM) was used to test the mediation effects. RESULTS: Resilience and self-esteem were found to be mediators of all three types of childhood abuse (emotional abuse, physical abuse and sexual abuse) when the types were examined separately; however, when all three types of childhood abuse were entered into the model simultaneously, neither the indirect effects nor direct effects of physical abuse or sexual abuse were found to be significant, only the association between emotional abuse and BPD features was partially mediated by resilience and self-esteem. CONCLUSIONS: Self-esteem and resilience mediate the links between childhood abuse and BPD features, and emotional abuse is uniquely associated with BPD features.


Assuntos
Transtorno da Personalidade Borderline , Maus-Tratos Infantis , Transtorno da Personalidade Borderline/etiologia , Criança , China , Estudos Transversais , Humanos , Estudantes
6.
Drug Deliv ; 28(1): 1419-1431, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34223777

RESUMO

Glucocorticoid (GC) hormone has been commonly used to treat systemic inflammation and immune disorders. However, the side effects associated with long-term use of high-dose GC hormone limit its clinical application seriously. GC hormone that can specifically target the lung might decrease the effective dosage and thus reduce GC-associated side effects. In this study, we successfully prepared human lung-targeting liposomal methylprednisolone crosslinked with nanobody (MPS-NSSLs-SPANb). Our findings indicate that MPS-NSSLs-SPANb may reduce the effective therapeutic dosage of MPS, achieve better efficacy, and reduce GC-associated side effects. In addition, MPS-NSSLs-SPANb showed higher efficacy and lower toxicity than conventional MPS.

7.
Bioorg Med Chem ; 29: 115849, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33221063

RESUMO

Neothalfine is a natural bisbenzylisoquinoline alkaloid with the abundant resource in medicinal plants and has not been reported its anti-tumor efficacy. In the present study, the anti-tumor efficacy was investigated and it showed broad-spectrum activity against several cancer cell lines, especially metastatic colorectal cancer (HCT116, SW620, T84) with the IC50 values of 7.2, 5.9, 8.2 nM, respectively, roughly equal to well-known anti-tumor agent docetaxel (4.0, 4.7, 2.7 nM) and nearly 1000 folds than CPT-11 (4.4, 5.1, 6.9 µM). Furthermore, neothalfine inhibited colorectal cell proliferation by resulting in cell cycle arrest at the G2/M phase and induced apoptosis through the dysfunction of mitochondria to trigger intrinsic apoptotic pathway by untargeted metabolomic method, mitochondrial membrane potential, and caspase-3/7 activity assay. Moreover, neothalfine damaged colorectal cancer clonal spheres expansion significantly at the concentration of 3.5 nM with nearly 1000 folds efficacy than CPT-11 (3.0 µM). The results supported that neothalfine might be an anti-tumor lead for further investigation.

8.
J Affect Disord ; 280(Pt B): 30-38, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33221605

RESUMO

BACKGROUND: A certain link between sexual abuse (SA) victimization and suicidal behaviors has been confirmed, but it remains unclear whether this association varies with regard to SA characteristics and gender. METHODS: Participants were 4034 college students drawn from a cross-sectional study conducted in Hefei, China. Gender-stratified latent class analysis (LCA) and logistic regression models were used to examine the relationships between timing, duration, types and patterns of SA victimization and suicidal behaviors. RESULTS: For the males, SA in the elementary school or earlier period was associated with suicidal ideation (OR: 3.29, 95%CI: 2.20-5.38), plans (OR: 3.44, 95% CI: 1.54-7.77) and preparations (OR:3.05, 95% CI: 1.19-7.74). All types of SA were significantly associated with the four types of suicidal behaviors. Dose-response relationship and cumulative effect were found between duration, types of SA victimization and suicidal behaviors. Three latent classes of SA victimization were identified for males and females, respectively. For males, the "moderate SA" class and "persistent SA" class were associated with the four types of suicidal behaviors. For the females, SA during the university period was associated with suicidal ideation (OR: 2.47, 95% CI: 1.24-4.93). Only suicidal ideation was associated with the "moderate SA" class. LIMITATIONS: The cross-sectional survey design did not allow to conclude any causality. CONCLUSIONS: The relationship between SA victimization and suicidal behaviors varies in terms of SA victimization characteristics and the relationships were stronger in males than in females.


Assuntos
Vítimas de Crime , Delitos Sexuais , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Estudantes , Ideação Suicida , Inquéritos e Questionários
9.
J Integr Plant Biol ; 63(4): 755-771, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33325122

RESUMO

In eukaryotes, MEDIATOR is a conserved multi-subunit complex that links transcription factors and RNA polymerase II and that thereby facilitates transcriptional initiation. Although the composition of MEDIATOR has been well studied in yeast and mammals, relatively little is known about the composition of MEDIATOR in plants. By affinity purification followed by mass spectrometry, we identified 28 conserved MEDIATOR subunits in Arabidopsis thaliana, including putative MEDIATOR subunits that were not previously validated. Our results indicated that MED34, MED35, MED36, and MED37 are not Arabidopsis MEDIATOR subunits, as previously proposed. Our results also revealed that two homologous CBP/p300 histone acetyltransferases, HAC1 and HAC5 (HAC1/5) are in fact plant-specific MEDIATOR subunits. The MEDIATOR subunits MED8 and MED25 (MED8/25) are partially responsible for the association of MEDIATOR with HAC1/5, MED8/25 and HAC1/5 co-regulate gene expression and thereby affect flowering time and floral development. Our in vitro observations indicated that MED8 and HAC1 form liquid-like droplets by phase separation, and our in vivo observations indicated that these droplets co-localize in the nuclear bodies at a subset of nuclei. The formation of liquid-like droplets is required for MED8 to interact with RNA polymerase II. In summary, we have identified all of the components of Arabidopsis MEDIATOR and revealed the mechanism underlying the link of histone acetylation and transcriptional regulation.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Flores/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Arseniato Redutases/genética , Arseniato Redutases/metabolismo , Flores/genética , Regulação da Expressão Gênica de Plantas , Histonas/genética , Histonas/metabolismo , Complexo Mediador/genética , Complexo Mediador/metabolismo , Plantas Geneticamente Modificadas/genética , RNA Polimerase II/genética , RNA Polimerase II/metabolismo
10.
J Interpers Violence ; : 886260520963709, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33001763

RESUMO

Little is known about the life course prevalence of bullying among university students. The current study examined the prevalence of bullying in different life periods among multi-university students. Our study included 4,034 university students from four types of universities. Participants self-reported four types of bullying (i.e., physical, verbal, relational, and cyber) with bullies and victims, and four periods (i.e., primary school or earlier, middle school, high school, and postsecondary education). Overall, the percentage of university students experiencing at least one type of bullying victimization (BV) and bullying perpetration (BP) during their lifetime was 59.7% and 31.6%, respectively; the percentage of the university students experiencing more than two types of BV and BP was 16.3% and 7.4%, respectively. The prevalence rates of each type of BV and BP were the highest in elementary school or earlier, and these rates decreased from elementary school or earlier to postsecondary education period. Four latent classes were identified for BV: low BV (73.8%), moderate BV (18.6%), secondary school BV (4.4%), and persistent BV (3.2%). Similarly, four classes for BP were identified: low BP (86.6%), primary school BP (8.1%), high school BP (1.5%), and persistent BP (3.8%). These findings may inform school health practice of bullying prevention by taking prevention programs, especially during elementary school or earlier period.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32595744

RESUMO

Radiation enteritis is a common side effect of radiotherapy for abdominal and pelvic malignancies, which can lead to a decrease in patients' tolerance to radiotherapy and the quality of life. It has been demonstrated that glycyrrhizin (GL) possesses significant anti-inflammatory activity. However, little is known about its anti-inflammatory effect in radiation enteritis. In the present study, we aimed to investigate the potential anti-inflammatory effects of GL on radiation enteritis and elucidate the possible underlying molecular mechanisms involved. The C57BL/6 mice were subjected to 6.5 Gy abdominal X-ray irradiation to establish a model of radiation enteritis. Hematoxylin and eosin staining was performed to analyze the pathological changes in the jejunum. The expression of TNF-α in the jejunum was analyzed by immunochemistry. The levels of inflammatory cytokines, such as TNF-α, IL-6, IL-1ß, and HMGB1 in the serum were determined by enzyme-linked immunosorbent assay. The intestinal absorption capacity was tested using the D-xylose absorption assay. The levels of HMGB1 and TLR4 were analyzed by western blotting and immunofluorescence staining. We found that GL significantly alleviated the intestinal damage and reduced the levels of inflammatory cytokines, such as TNF-α, IL-6, IL-1ß, and HMGB1 levels. Furthermore, the HMGB1/TLR4 signaling pathway was significantly downregulated by GL treatment. In conclusion, these findings indicate that GL has a protective effect against radiation enteritis through the inhibition of the intestinal damage and the inflammatory responses, as well as the HMGB1/TLR4 signaling pathway. Thereby, GL might be a potential therapeutic agent for the treatment of radiation enteritis.

12.
Sci Rep ; 10(1): 3094, 2020 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-32080227

RESUMO

Involvement of long non-coding RNAs (lncRNAs) in the regulation of gene expression in cis has been well studied in eukaryotes but relatively little is known whether and how lncRNAs affect gene expression in tans. In Arabidopsis thaliana, COLDAIR, a previously reported lncRNA, is produced from the first intron of FLOWERING LOCUS C (FLC), which encodes a repressor of flowering time. Our results indicated that the exogenously overexpressed COLDAIR enhances the expression of FLC in trans, resulting in a late-flowering phenotype. In 35S-COLDAIR lines, the enhanced expression of FLC is correlated with the down-regulation of the repressive histone mark H3K27me3 and with the up-regulation of the active histone mark H3K4me3 at the FLC chromatin. Furthermore, we demonstrated that overexpression of intronic lncRNAs from several other H3K27me3-enriched MADS-box genes also activates the expression of their host genes. This study suggests that the involvement of overexpressed intronic lncRNAs in gene activation may be conserved in H3K27me3-enriched genes in eukaryotes.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Código das Histonas , Histonas/química , RNA Longo não Codificante/genética , Arabidopsis/fisiologia , Regulação para Baixo , Flores/fisiologia , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Histonas/genética , Íntrons , Proteínas de Domínio MADS/genética , Peptídeos/química , Fenótipo , RNA de Plantas/genética , Transcriptoma
13.
Biochem Biophys Res Commun ; 524(1): 77-82, 2020 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-31980179

RESUMO

OBJECTIVES: Protein arginine methyltransferase 2 (PRMT2) is closely related to the occurrence and development of atherosclerosis. However, its underlying mechanisms remain to be elucidated. The purpose of this study is to observe the effect of overexpression of PRMT2 on the formation of foam cells and to explore its possible mechanism in RAW 264.7 macrophage. METHODS: Lentivirus vector of overexpression PRMT2 (LV-PRMT2) was constructed. LV-PRMT2 and lentivirus vector GV492 were transfected into RAW 264.7 macrophages, positive clone cells were screened by treatment with 4.0 µg/mL puromycin for 4 weeks. The macrophages were treated with ox-LDL (50 µg/mL) for 48 h to induce foaming. The lipid accumulation of macrophages was observed by oil red O staining. The levels of cellular total cholesterol (TC), free cholesterol (FC) and cholesteryl ester (CE) were measured by high performance liquid chromatography (HPLC) assays. The cholesterol efflux of macrophages was tested by the [3H] labeled cholesterol. The expressions of ATP binding cassette transporter A1 (ABCA1), ATP binding cassette transporter G1 (ABCG1), CD36 and scavenger receptor A1 (SR-A1) in macrophages were measured by Western Blot. RESULTS: The results showed that LV-PRMT2 and lentivirus vector has been successfully transfected into RAW 264.7 macrophage. Compared with the Vector group, the mRNA and protein expressions of PRMT2 were significantly up-regulated (P < 0.05). Compared with Control group, the expression of PRMT2 was significantly down-regulated in ox-LDL group (P < 0.05). A large number of red lipid droplets appeared in the cells in Vector group. Compared with Vector group, lipid droplets, the levels of TC, FC and CE and CE/TC, cholesterol efflux rate and expression of ABCA1 in RAW 264.7 macrophage was significantly decreased in LV-PRMT2 group (all P < 0.05). There was no significant difference about the expressions of ABCG1, CD36 and SR-A1 between LV-PRMT2 group and Vector group (all P > 0.05). CONCLUSIONS: Overexpression of PRMT2 inhibits the formation of foam cell induced by ox-LDL in RAW 264.7 macrophage, and the mechanism may be related to the increase of ABCA1 expression and ABCA1 mediated cholesterol efflux.


Assuntos
Transportador 1 de Cassete de Ligação de ATP/metabolismo , Células Espumosas/metabolismo , Lipoproteínas LDL/metabolismo , Proteína-Arginina N-Metiltransferases/metabolismo , Transportador 1 de Cassete de Ligação de ATP/genética , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Arginina/metabolismo , Aterosclerose/metabolismo , Transporte Biológico , Antígenos CD36/metabolismo , Regulação da Expressão Gênica , Lentivirus/genética , Metilação , Camundongos , Células RAW 264.7 , RNA Mensageiro/metabolismo , Receptores Depuradores/metabolismo , Transfecção
14.
Transplant Proc ; 52(1): 54-60, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31901324

RESUMO

BACKGROUND: Kidneys at higher risk for allograft failure are defined by the Kidney Donor Profile Index (KDPI) > 85% in the current kidney allocation system (KAS), replacing the historical concept of expanded criteria donor (ECD) kidneys in the previous KAS. Discrepancies exist in the classification of "high-risk kidneys" between the 2 KAS. In the current KAS, only recipients of KDPI > 85% kidneys are counseled about the high risk of allograft failure and are required to sign a consent. In this study, we evaluated the outcomes and allocation of kidneys with discordant classification. METHODS: Using the Scientific Registry of Transplant Recipients, kidneys transplanted between 01/2002 and 09/2016 were classified according to the old (standard criteria donor [SCD]/ECD) and current (KDPI) KAS. We then grouped them as concordant (KDPI ≤ 85% + SCD or KDPI > 85% + ECD) and discordant (KDPI ≤ 85% + ECD or KDPI > 85% + SCD) kidneys. RESULTS: Approximately 11% of transplanted kidneys were discordant in classification. Among kidneys with KDPI ≤ 85%, ECD status conferred a 64% (95% CI: 56%-73%) higher risk of allograft failure compared to SCD status. However, SCD/ECD status was not associated with differential outcomes in KDPI > 85% kidneys. These ECD kidneys have KDPIs > 50% and have been transplanted across all estimated post-transplant survival (EPTS) deciles. CONCLUSION: Adequate counseling about the risk and benefit of accepting ECD kidneys with KDPI ≤ 85% versus waiting on dialysis should be explored with the patients, especially those with lower EPTS.


Assuntos
Transplante de Rim , Seleção de Pacientes , Doadores de Tecidos/provisão & distribuição , Transplantes/classificação , Transplantes/provisão & distribuição , Adulto , Feminino , Sobrevivência de Enxerto , Humanos , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Transplantados/classificação
15.
Pest Manag Sci ; 76(3): 1071-1077, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31515949

RESUMO

BACKGROUND: Discovery of novel insecticides and targets has received global attention in recent years. Ten genes coding for enzymes involved in the juvenile hormone biosynthetic pathway of Manduca sexta were studied as potential insecticide targets. RESULTS: We determined the expression of genes encoding some critical enzymes in the JH biosynthetic pathway. Farnesol dehydrogenase (FOLD), Juvenile hormone acid O-methyltransferase (JHAMT) and Juvenile hormone epoxidase (CYP15C1) were selected as the candidate targets based on gene expression results. RNAi silencing and enzyme inhibitor tests were performed to validate whether these candidate genes could be the potential insecticide targets. The down-regulation of FOLD, JHAMT and CYP15C1 resulted in a 68%, 82% and 79% reduction in the rates of JH biosynthesis in vitro, respectively. In addition, RNA interference and inhibitor studies of these enzymes following oral administration demonstrated the potential application in pest management, with respect to high mortality and effects on growth. CONCLUSION: Based on our study, FOLD, JHAMT and CYP15C1 could be potential targets for pest control as a consequence of their important roles in insect development. © 2019 Society of Chemical Industry.


Assuntos
Vias Biossintéticas , Hormônios Juvenis , Metiltransferases , Controle de Pragas , Interferência de RNA
16.
Psychiatr Q ; 90(3): 471-480, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31079346

RESUMO

Cognitive deficits are a core feature of major depressive disorder (MDD). However, there are no previous studies that directly compare cognitive performance between first-episode drug-naive depressive patients (FDDP) and medicated depressive patients (MDP). Therefore, the aim of this study was to investigate whether there were the differences in cognitive functions between FDDP and MDP. Sixty-two FDDP, 111 MDP and 90 healthy controls were enrolled in a Chinese population. Cognitive functions were assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). There were the differences in the RBANS total score (F = 26.55, p < 0.001), subscales of immediate memory (F = 3.95, p = 0.02), language (F = 54.11, p < 0.001) and delayed memory (F = 11.19, p = 0.001) among the three groups after controlling for gender, education, smoking and body mass index (BMI). These differences in the RBANS total score, subscales of language and delayed memory passed the Bonferroni corrections (all, p < 0.05). Compared to healthy controls, FDDP and MDP had poorer cognitive performance including the RBANS total score, and subscales of language and delayed memory (all, p < 0.05) after controlling for the variables. FDDP experienced greater language deficits than MDP (p < 0.05) after controlling for the variables. Education was correlated with the language score in FDDP (r = 0.61, p < 0.001). Multivariate regression analysis indicated that education was an independent contributor to the language score in FDDP (ß = 3.11, t = 5.48, p < 0.001). Our findings indicated that FDDP had poorer language performance than MDP. Moreover, education could influence the language performance in FDDP.


Assuntos
Cognição , Disfunção Cognitiva/complicações , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/psicologia , Adolescente , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/psicologia , Estudos de Casos e Controles , Disfunção Cognitiva/psicologia , Transtorno Depressivo Maior/tratamento farmacológico , Escolaridade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Adulto Jovem
17.
Environ Toxicol Pharmacol ; 68: 13-18, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30852303

RESUMO

Alternate forms of drug crystals display different physicochemical properties. These include stability, dissolution rate, bioavailability and solubility, which can affect pharmacokinetics and pharmacodynamics. It is therefore important to compare the crystal forms of cedrol to obtain optimal anti-inflammatory and analgesic effects. This study, for the first time, obtained and reports three novel forms (I-III) of cedrol polymorphs. The three forms of cedrol were recrystallized from seven organic solvents by slow cooling or volatilization and identified by thermal analysis, fourier transform infrared spectroscopy, scanning electron microscopy and powder X-ray diffraction analysis. Form I originated from acetone and cyclohexane. Form II was obtained from ethanol, ethyl acetate, acetonitrile and n-hexane. Form III was recrystallized from methanol. The anti-inflammatory and analgesic activities of the three crystalline forms were evaluated by acetic acid induced writhing in mice, the hot plate method, carrageenan induced mouse paw edema models, Xylene-induced mouse ear edema models and cotton pellet-induced mouse granuloma models. Experimental results revealed that the highest performance was achieved from Form I. These findings are of great significance during the early research study of cedrol polymorphs.


Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Edema/tratamento farmacológico , Granuloma/tratamento farmacológico , Dor/tratamento farmacológico , Terpenos/uso terapêutico , Ácido Acético , Animais , Carragenina , Fibra de Algodão , Edema/induzido quimicamente , Feminino , Temperatura Alta , Camundongos , Dor/induzido quimicamente , Sesquiterpenos Policíclicos , Xilenos
18.
Mediators Inflamm ; 2019: 5160694, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30718973

RESUMO

Background: Acute exacerbation of IPF (AE-IPF) is associated with high mortality. We studied changes in pathogen involvement during AE-IPF and explored a possible role of infection in AE-IPF. Objectives: Our purpose is to investigate the role of infection in AE-IPF. Methods: Overall, we recruited 170 IPF patients (48 AE-IPF, 122 stable) and 70 controls at Shanghai Pulmonary Hospital. Specific IgM against microbial pathogens and pathogens in sputum were assessed. RNA sequences of pathogens in nasopharyngeal swab of IPF patients were detected by PathChip. A panel of serum parameters reflecting immune function were assessed. Results: Antiviral/bacterial IgM was higher in IPF vs. controls and in AE-IPF vs. stable IPF. Thirty-eight different bacterial strains were detected in IPF patient sputum. Bacteria-positive results were found in 9/48 (18.8%) of AE-IPF and in 26/122 (21.3%) stable IPF. Fifty-seven different viruses were detected in nasopharyngeal swabs of IPF patients. Virus-positive nasopharyngeal swabs were found in 18/30 (60%) of tested AE-IPF and in 13/30 (43.3%) of stable IPF. AE-IPF showed increased inflammatory cytokines (IL-6, IFN-γ, MIG, IL-17, and IL-9) vs. stable IPF and controls. Mortality of AE-IPF in one year (39.5%) was higher compared to stable IPF (28.7%).Conclusions. IPF patients had different colonization with pathogens in sputum and nasopharyngeal swabs; they also displayed abnormally activated immune response, which was exacerbated during AE-IPF.


Assuntos
Fibrose Pulmonar Idiopática/sangue , Fibrose Pulmonar Idiopática/complicações , Infecções/sangue , Infecções/complicações , Idoso , China , Citocinas/sangue , Feminino , Humanos , Imunoglobulina M/imunologia , Imunossupressão , Inflamação , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , RNA Viral/isolamento & purificação , Análise de Sequência de RNA , Escarro/microbiologia , Escarro/virologia
19.
J Cell Mol Med ; 23(2): 908-919, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30378252

RESUMO

BACKGROUND: Patients with idiopathic pulmonary fibrosis (IPF) often experience acute exacerbation (AE) after an episode of common cold. AIMS: To establish a mouse model of virus infection-induced AE-IPF and investigate the mechanism underlying the AE-IPF. METHODS: Herpes simplex virus 1 (HSV1) was inoculated intranasally to wild-type (WT) and IL-17A gene knockout (IL-17A-/- ) mice 21 days after intratracheal administration of bleomycin (BLM). RESULTS: HSV1 infection caused acute exacerbation in mice with BLM-induced fibrosis. Compared with the BLM+Saline mice, the mice with BLM+HSV1 showed significantly higher acute lung injury (ALI) score (P < 0.0001), lower survival rate (100% vs 21.4%, P < 0.0001), poorer lung function and higher inflammatory response representing by increased total inflammatory cells in bronchoalveolar lavage fluid (BALF) (P = 0.0323), increased proportion of Th17 cells in peripheral blood (P = 0.0004) and higher inflammatory factors in BALF. In addition, HSV1 infection increased the expression of endoplasmic reticulum stress (ERS)-related proteins in mice with BLM-induced fibrosis. The inhibition of ERS by tauroursodeoxycholic acid (TUDCA, an ERS inhibitor) significantly reduced the IL-17A levels in BALF (P = 0.0140) and TH17 cells in the peripheral blood (P = 0.0084) of mice with BLM+HSV1, suggesting that suppression of ERS may reduce TH17 response in mice with AE-IPF. Compared with WT mice with BLM+HSV1, IL-17A-/- mice with BLM+HSV1 had lower ALI score (P = 0.0119), higher survival rate (78.6% vs 21.4%, P = 0.004), improved lung function, and milder inflammatory response. CONCLUSIONS: HSV1 infection in addition to BLM-induced IPF can successfully establish AE-IPF in mice. IL-17A and ERS promote lung inflammation in AE-IPF development.


Assuntos
Lesão Pulmonar Aguda/virologia , Estresse do Retículo Endoplasmático/imunologia , Herpes Simples/virologia , Fibrose Pulmonar Idiopática/virologia , Interleucina-17/genética , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/mortalidade , Animais , Anti-Inflamatórios/farmacologia , Antivirais/farmacologia , Bleomicina , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/imunologia , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Estresse do Retículo Endoplasmático/genética , Expressão Gênica , Herpes Simples/induzido quimicamente , Herpes Simples/tratamento farmacológico , Herpes Simples/mortalidade , Herpesvirus Humano 1 , Humanos , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/mortalidade , Interleucina-17/deficiência , Interleucina-17/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Testes de Função Respiratória , Análise de Sobrevida , Ácido Tauroquenodesoxicólico/farmacologia , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Células Th17/virologia
20.
Am J Physiol Cell Physiol ; 316(6): C782-C791, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30540496

RESUMO

Cell permeability and epithelial-mesenchymal transition (EMT) were found to be enhanced in diabetic retinopathy, and the aim of this study was to investigate the underlying mechanism. ARPE-19 cell line or primary retinal pigment epithelial (RPE) cells were cultured under high or normal glucose conditions. Specific shRNAs were employed to knock down ADP-ribosylation factor 6 (ARF6), GEP100, or VEGF receptor 2 (VEGFR2) in ARPE-19 or primary RPE cells. Cell migration ability was measured using Transwell assay. Western blotting was used to measure indicated protein levels. RPE cells treated with high glucose showed increased cell migration, paracellular permeability, EMT, and expression of VEGF. Knockdown of VEGFR2 inhibited the high-glucose-induced effects on RPE cells via inactivation of ARF6 and MAPK pathways. Knockdown ARF6 or GEP100 led to inhibition of high-glucose-induced effects via inactivation of VEGFR2 pathway. Knockdown of ARF6, but not GEP100, decreased high-glucose-induced internalization of VEGFR2. High-glucose enhances EMT and cell permeability of RPE cells through activation of VEGFR2 and ARF6/GEP100 pathways, which form a positive feedback loop to maximize the activation of VEGF/VEGFR2 signaling.


Assuntos
Fatores de Ribosilação do ADP/metabolismo , Transição Epitelial-Mesenquimal/fisiologia , Glucose/administração & dosagem , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Animais , Permeabilidade da Membrana Celular/efeitos dos fármacos , Permeabilidade da Membrana Celular/fisiologia , Células Cultivadas , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Glucose/toxicidade , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Epitélio Pigmentado da Retina/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
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