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Context: Hydrocephalus refers to excessive secretion of cerebrospinal fluid, its insufficient absorption, or its blocked circulation and frequently occurs after a cerebral hemorrhage. The mortality and disability rates for cerebral hemorrhage are high. Objective: The study intended to evaluate the clinical efficacy of integrated traditional Chinese and Western medicine in the treatment of hydrocephalus after a cerebral hemorrhage, using systematic screening and analysis of published literature. Design: The research team performed a meta-analysis by searching databases-PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang database, and Chinese Biomedical Literature-and collected Chinese and English publications from the establishment of each database until December 2022 discussing studies that used a TCM treatment that promoted blood circulation and removed blood stasis, combined with conventional western medicine, for hydrocephalus after cerebral hemorrhage. The keywords were promoting blood circulation and removing blood stasis, cerebral hemorrhage, and hydrocephalus. The team performed the meta-analysis using RevMan 5.3. Results: The research team found five relevant studies, all of which were randomized controlled trials. The clinical efficacy TCM combined with conventional Western medicine was significantly better than that of other treatments [MD = 1.77, 95% CI (0.23, 3.31), Z = 12.18, P < .001]. The NIHSS score after the integrated treatments also improved significantly more than those of other treatments [MD = -2.54, 95% CI (-4.07, -1.01), Z = 5.16, P < .00001]. Conclusions: Activating blood circulation and removing blood stasis using TCM, combined with conventional Western medicine, can achieve ideal therapeutic effects for patients with hydrocephalus after a cerebral hemorrhage, which can have a positive influence on clinical efficacy and reduce the NIHSS score, and the combined treatments have a clinical value.
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Medicamentos Herbarios Chinos , Hidrocefalia , Humanos , Medicamentos Herbarios Chinos/uso terapéutico , Medicina Tradicional China/métodos , Resultado del Tratamiento , Hidrocefalia/etiología , Hidrocefalia/inducido químicamente , Hemorragia Cerebral/inducido químicamente , Hemorragia Cerebral/tratamiento farmacológicoRESUMEN
BACKGROUND: Although many studies showed that the risk of congenital heart disease (CHD) was closely related to genetic factors, the exact pathogenesis is still unknown. Our study aimed to comprehensively assess the association of single nucleotide polymorphisms (SNPs) of maternal MTHFR gene with risk of CHD and its three subtypes in offspring. METHODS: A case-control study involving 569 mothers of CHD cases and 652 health controls was conducted. Thirteen SNPs were detected and analyzed. RESULTS: Our study showed that genetic polymorphisms of maternal MTHFR gene at rs4846052 and rs1801131 were significantly associated with risk of CHD in the homozygote comparisons (TT vs. CC at rs4846052: OR = 7.62 [95%CI 2.95-19.65]; GG vs. TT at rs1801131: OR = 5.18 [95%CI 2.77-9.71]). And six haplotypes of G-C (involving rs4846048 and rs2274976), A-C (involving rs1801133 and rs4846052), G-T (involving rs1801133 and rs4846052), G-T-G (involving rs2066470, rs3737964 and rs535107), A-C-G (involving rs2066470, rs3737964 and rs535107) and G-C-G (involving rs2066470, rs3737964 and rs535107) were identified to be significantly associated with risk of CHD. Additionally, we observed that a two-locus model involving rs2066470 and rs1801131 as well as a three-locus model involving rs227497, rs1801133 and rs1801131 were significantly associated with risk of CHD in the gene-gene interaction analyses. For three subtypes including atrial septal defect, ventricular septal defect and patent ductus arteriosus, similar results were observed. CONCLUSIONS: Our study indicated genetic polymorphisms of maternal MTHFR gene were significantly associated with risk of fetal CHD in the Chinese population. Additionally, there were significantly interactions among different SNPs on risk of CHD. However, how these SNPs affect the development of fetal heart remains unknown, and more studies in different ethnic populations and with a larger sample are required to confirm these findings.
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Cardiopatías Congénitas/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Polimorfismo de Nucleótido Simple , Adulto , Estudios de Casos y Controles , China , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Haplotipos , Cardiopatías Congénitas/diagnóstico , Heterocigoto , Homocigoto , Humanos , Desequilibrio de Ligamiento , Fenotipo , Embarazo , Medición de Riesgo , Factores de RiesgoRESUMEN
Although it is generally recognized that genetic and environmental factors are associated with the risk of congenital heart disease (CHD), the mechanism remains largely uncertain. This study aimed to investigate the association of maternal folate use, the time when folate use was started, and polymorphisms of the reduced folate carrier (RFC1) gene with the risk of CHD in offspring of Chinese descent, which can help provide new insight into the etiology of folate-related birth defects. A case-control study of 683 mothers of CHD patients and 740 mothers of healthy children was performed. The present study showed that mothers who did not use folate were at a significantly increased risk of CHD (OR=2.04; 95% CI: 1.42-2.93). When compared with those who started using folate prior to conception, mothers who started using folate from the first trimester of pregnancy (OR=1.90; 95% CI: 1.43-2.54) or from the second trimester of pregnancy (OR=8.92; 95% CI: 4.20-18.97) had a significantly higher risk of CHD. Maternal RFC1 gene polymorphisms at rs2236484 (AG vs AA: OR=1.79 [95% CI: 1.33-2.39]; GG vs AA: OR=1.64 [95% CI: 1.15-2.35]) and rs2330183 (CT vs CC: OR=1.54 [95% CI: 1.14-2.09]) were also significantly associated with CHD risk. Additionally, the risk of CHD was significantly decreased among mothers who had variant genotypes but used folate when compared with those who had variant genotypes and did not use folate.Conclusion: In those of Chinese descent, maternal folate use and the time when use started are significantly associated with the risk of CHD in offspring. Furthermore, maternal folate supplementation may help to offset some of the risks of CHD in offspring due to maternal RFC1 genetic variants. What is Known: ⢠Folate use could help prevent CHD, but the relationship between the time when folate use is started and CHD has not received sufficient attention. ⢠Studies have assessed the associations of folate metabolism-related genes with CHD, but genes involved in cellular transportation of folate, such as the RFC1 gene, have not garnered enough attention. What is New: ⢠In those of Chinese descents, the time when folate use is started is significantly associated with the risk of CHD in offspring. ⢠Maternal RFC1 polymorphisms were significantly associated with the risk of CHD. ⢠Folate supplementation may help to offset some risks of CHD due to RFC1 genetic variants.
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Ácido Fólico , Cardiopatías Congénitas , Proteína Portadora de Folato Reducido/genética , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Cardiopatías Congénitas/genética , Humanos , Madres , Polimorfismo Genético , Factores de RiesgoRESUMEN
Objective To evaluate the effects of antiretroviral therapy(ART)for the prevention of mother-to-child transmission(PMTCT)of acquired immune deficiency syndrome(AIDS)on the growth and development of 18-month-old children born by human immunodeficiency virus(HIV)-positive pregnant women in Lingshan County,Guangxi Zhuang Autonomous Region,and provide scientific evidence for improving the ART medication plan for PMTCT.Methods Lingshan County,ranking the first in the HIV-epidemic counties of Guangxi,was selected as the research site.According to the design of retrospective case-control study,we assigned all the subjects into the case group and the control group:(1)The case group included the HIV-positive pregnant women who had received ART for PMTCT and their HIV-negative infants in Lingshan County from 2010 to 2017.The historical cards and PMTCT data of them were collected from the national PMTCT database.(2)The control group included the healthy pregnant women and their healthy babies born in the Lingshan Maternity and Infant Hospital in 2017,and the children's growth and development data were collected.The stunted growth in children was defined as at least one of the three main indicators of body height,body weight,and head circumference below the normal range.Results The number of HIV-positive mothers and their infants in the case group was 391 and 368,respectively,and 87.21%(341/391)and 95.38%(351/368)of mothers and infants respectively received ART medication.The HIV positive rate,mortality rate,and mother-to-child transmission rate of 18-month-old children were 1.36%(5/368),4.35%(16/368),and 2.01%(5/249),respectively.The incidence of stunted growth of 18-month-old children in the case group and the control group was 42.12%(155/368)and 23.06%(101/438),respectively,with significant difference(χ2=33.520,P<0.001).Conclusion After HIV-positive mothers in Lingshan County of Guangxi received ART for PMTCT,the incidence of growth stunting in 18-month-old children increased.
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Infecciones por VIH , Complicaciones Infecciosas del Embarazo , Estudios de Casos y Controles , China/epidemiología , Femenino , Crecimiento y Desarrollo , VIH , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Humanos , Lactante , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Madres , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
OBJECTIVE: To study the association between maternal reduced folate carrier (RFC) gene polymorphisms and congenital heart disease (CHD) in offspring. METHODS: A hospital-based case-control study was conducted. The mothers of 683 infants with CHD who attended the Department of Cardiothoracic Surgery, Hunan Children's Hospital, from November 2017 to March 2020 were enrolled as the case group. The mothers of 740 healthy infants without any deformity who attended the hospital during the same period of time were enrolled as the control group. A questionnaire survey was performed to collect the exposure data of subjects. Venous blood samples of 5 mL were collected from the mothers for genetic polymorphism detection. A multivariate logistic regression analysis was used to evaluate the association of RFC gene polymorphisms and their haplotypes with CHD. A generalized multifactor dimensionality reduction method was used to analyze gene-gene interactions. RESULTS: After control for confounding factors, the multivariate logistic regression analysis showed that maternal RFC gene polymorphisms at rs2236484 (AG vs AA:OR=1.91, 95%CI:1.45-2.51; GG vs AA: OR=1.96, 95%CI:1.40-2.75) and rs2330183 (CT vs CC:OR=1.39, 95%CI:1.06-1.83) were significantly associated with the risk of CHD in offspring. The haplotypes of G-G (OR=1.21, 95%CI:1.03-1.41) and T-G (OR=1.25, 95%CI:1.07-1.46) in mothers significantly increased the risk of CHD in offspring. The interaction analysis showed significant gene-gene interactions between different SNPs of the RFC gene in CHD (P < 0.05). CONCLUSIONS: Maternal RFC gene polymorphisms and interactions between different SNPs are significantly associated with the risk of CHD in offspring.
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Cardiopatías Congénitas , Polimorfismo de Nucleótido Simple , Estudios de Casos y Controles , Niño , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Cardiopatías Congénitas/genética , Humanos , Lactante , Proteína Portadora de Folato Reducido/genética , Factores de RiesgoRESUMEN
OBJECTIVE: The relationship between NF-κB Interacting lncRNA (NKILA) and angiogenesis in breast cancer has never been studied. Our study aimed to investigate effect of NKILA on proliferation, migration, apoptosis, as well as angiogenesis in breast cancer. METHODS: NKILA was over-expressed in MDA-MB-231 cells by transfection of pcDNA3.1-NKILA vector. Cell viability, apoptosis and migration were measured by MTT, flow cytometry and wound healing assays, respectively. Angiogenesis of human umbilical vein endothelial cells (HUVEC) was measured using tube formation assay. The expression levels of NKILA, IL-6, VEGFA, VEGFR, apoptosis and epithelial-mesenchymal transition (EMT) and NF-κB/IL-6 signaling-related markers were determined using qRT-PCR or Western blotting. RESULTS: Cell viability and migration of MDA-MB-231 cells were significantly inhibited, while cell apoptosis was obviously promoted by overexpression of NKILA. Overexpression of NKILA could also inhibit the phosphorylation of IκBα and the nuclear transposition of p65, as well as induce cell apoptosis-related proteins and inhibit epithelial-mesenchymal transition-related proteins. Cell viability and migration of HUVEC were also significantly inhibited when treated with supernatant of cells overexpressed NKILA or treated with BAY11-7028. Exogenous IL-6 significantly increased the cell viability and migration of HUVEC, and overexpression of NKILA could reverse these effects induced by IL-6. Overexpression of NKILA significantly inhibited the protein levels of IL-6 and VEGFA in supernatant, as well as VEGFR in HUVEC, thus inhibited the angiogenesis of HUVEC. NKILA also reversed the above effects on protein levels of IL-6 and VEGFA in supernatant and angiogenesis induced by exogenous IL-6. CONCLUSION: Overexpression of NKILA could inhibit cell proliferation, migration and promote apoptosis of breast cancer cells. It could also inhibit cell proliferation, migration and angiogenesis of HUVEC through inhibiting IL-6 secretion via NF-κB signaling pathway.
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Neoplasias de la Mama/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Interleucina-6/metabolismo , FN-kappa B/metabolismo , Neovascularización Patológica , Neovascularización Fisiológica , ARN Largo no Codificante/metabolismo , Apoptosis , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Línea Celular Tumoral , Movimiento Celular , Transición Epitelial-Mesenquimal , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , ARN Largo no Codificante/genética , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
To assess the birth prevalence and spatial distribution of congenital heart disease (CHD) in China by conducting a complete overview and using spatial epidemiological methods. Unrestricted searches were conducted on seven electronic databases, with an end-date parameter of May 2019. Data on the birth prevalence of CHD and its subtypes were collected and combined using either the random-effect model or fixed-effect model. Subgroup sensitivity analyses were performed to explore potential heterogeneity moderators. The three-dimensional trend analysis and a visualization of CHD birth prevalence among different provinces were performed to describe the spatial distribution characteristics. Total 617 studies involving 76,961,354 births and 201,934 CHD individuals were included. Overall, total CHD birth prevalence increased continuously over time, from 0.201 in 1980-1984 to 4.905 in 2015-2019. The study on the high-income provinces, population-based monitoring model, male births, and urban regions reported a significantly higher prevalence of total CHD compared with upper-middle-income provinces, hospital-based monitoring model, female births, and rural regions, respectively. National CHD birth prevalence increased gradually from western region to eastern region, but decreased gradually from southern to northern region. Relevant heterogeneity moderators including gender, geographic region, income levels, and monitoring models have been identified by subgroup analyses. Sensitivity analysis yielded consistent results. Total CHD birth prevalence in China increases continuously in the past 40 years. Significant differences in gender, geographical regions, income levels, and monitoring models were found. In the future, population wide prospective birth defect registries covering the entire Chinese population need to determine the exact birth prevalence.
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Pueblo Asiatico/estadística & datos numéricos , Cardiopatías Congénitas/epidemiología , China/epidemiología , Femenino , Cardiopatías Congénitas/etnología , Humanos , Lactante , Recién Nacido , Masculino , Embarazo , PrevalenciaRESUMEN
AIM: The aim of the study was to review and summarize the epidemiologic evidence on the associations of homocysteine (HCY) and folate with the risk of recurrent spontaneous abortion (RSA). METHODS: This review was performed following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. PubMed, Google Scholar, Cochrane Libraries and Chinese databases were searched through May 2019 to identify studies that met prestated inclusion criteria. Either a fixed- or a random-effects model was used to calculate the combined standardized mean difference (SMD) and 95% confidence intervals (CI). RESULTS: Twenty-three studies involving 2052 RSA cases and 1476 healthy controls were included. Overall, women with RSA compared with those without RSA were at a significantly higher level of HCY both in plasma (SMD = 1.34; 95% CI: 0.76-1.93) and in serum (SMD = 1.46; 95% CI: 1.02-1.91), but lower level of folate both in serum (SMD = -1.63; 95% CI: -2.51 to -0.75) and in red blood cells (SMD = -1.30; 95% CI: -1.76 to -0.85). However, a statistically significant association between plasma folate and risk of RSA was not been observed (SMD = -0.82; 95% CI: -1.73 to 0.09). These findings have to be viewed with caution for the significant heterogeneity (I2 : from 88 to 98%). CONCLUSION: High HCY levels in both plasma and serum as well as low folate levels in serum and red blood cells are significantly associated with risk of RSA, which indicates that measures to reduce HCY levels or folate supplementation may help to reduce the risk of RSA. However, prospective studies are needed to confirm our findings.
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(-)-5-Epieremophilene, an epimer of the versatile sesquiterpene (+)-valencene, is an inaccessible natural product catalyzed by three sesquiterpene synthases (SmSTPSs1-3) of the Chinese medicinal herb Salvia miltiorrhiza, and its biological activity remains less explored. In this study, three metabolically engineered Escherichia coli strains were constructed for (-)-5-epieremophilene production with yields of 42.4-76.0â mg/L in shake-flask culture. Introducing an additional copy of farnesyl diphosphate synthase (FDPS) gene through fusion expression of SmSTPS1-FDPS or dividing the FDP synthetic pathway into two modules resulted in significantly improved production, and ultimately 250â mg of (-)-5-epieremophilene were achieved. Biological assay indicated that (-)-5-epieremophilene showed significant antifeedant activity against Helicoverpa armigera (EC50 =1.25â µg/cm2 ), a common pest of S. miltiorrhiza, implying its potential defensive role in the plant. The results provided an ideal material supply for studying other potential biological activities of (-)-5-epieremophilene, and also a strategy for manipulating terpene production in engineered E. coli using synthetic biology.
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Escherichia coli/metabolismo , Insecticidas/metabolismo , Ingeniería Metabólica , Sesquiterpenos/metabolismo , Transferasas Alquil y Aril/genética , Transferasas Alquil y Aril/metabolismo , Animales , Escherichia coli/química , Conducta Alimentaria/efectos de los fármacos , Insecticidas/química , Insecticidas/farmacología , Lepidópteros/efectos de los fármacos , Estructura Molecular , Salvia miltiorrhiza/enzimología , Sesquiterpenos/química , Sesquiterpenos/farmacologíaRESUMEN
OBJECTIVE: To study the association of maternal diabetes mellitus (DM), uncoupling protein 2 (UCP2) gene polymorphisms, and their interaction with the risk of congenital heart disease (CHD) in offspring. METHODS: A hospital-based case-control study was conducted. A total of 464 mothers of children with CHD alone who were diagnosed in Hunan Children's Hospital from March 2018 to August 2019 were enrolled as the case group. A total of 504 mothers of healthy children who were hospitalized during the same period and did not have any deformity were enrolled as the control group. A questionnaire survey was performed to collect the information on exposure. Venous blood samples (5â mL) were collected from the mothers to detect UCP2 gene polymorphisms. A multivariate logistic regression analysis was used to investigate the association of maternal DM, UCP2 gene polymorphisms, and their interaction with CHD in offspring. RESULTS: After control for confounding factors, the multivariate logistic regression analysis showed that mothers with gestational DM (OR=2.96, 95%CI: 1.57-5.59), a history of gestational DM (OR=3.16, 95%CI: 1.59-6.28), and pregestational DM (OR=4.52, 95%CI: 2.41-8.50) significantly increased the risk of CHD in offspring (P<0.05). The polymorphisms of the UCP2 gene at rs659366 (T/C vs C/C: OR=1.49, 95%CI: 1.02-2.16; T/T vs C/C: OR=2.77, 95%CI: 1.67-4.62) and rs660339 (A/A vs G/G: OR=2.19, 95%CI: 1.34-3.58) were significantly associated with risk of CHD in offspring (P<0.05). The interaction analysis showed an interaction between the polymorphisms of the UCP2 gene at rs659366 and rs660339 and maternal DM in the development of CHD (P<0.05). CONCLUSIONS: Maternal DM, UCP2 gene polymorphisms, and their interaction are associated with the development of CHD in offspring.
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Diabetes Gestacional , Cardiopatías Congénitas , Proteína Desacopladora 2/genética , Estudios de Casos y Controles , Niño , Femenino , Cardiopatías Congénitas/genética , Humanos , Polimorfismo Genético , EmbarazoRESUMEN
BACKGROUND: Host genetic factors affect the immune response to Mycobacterium tuberculosis (Mtb) infection as well as the progression of the disease. Epiregulin (EREG) belongs to the epidermal growth factor (EGF) family, which binds to the epidermal growth factor receptor (EGFR) to regulate the immune response of the host during infections. Our study aimed to compare EREG levels in tuberculosis (TB) patients and healthy controls and assess whether polymorphisms in EREG increase the risk of TB. METHODS: We used ELISA to determine the plasma EREG level from 30 healthy controls and 50 tuberculosis patients. By evaluating the EREG gene from 624 TB patients and 600 healthy controls, we determined the allelic and genotypic frequencies for association with susceptibility to TB infections in this group. RESULTS: This paper shows that the pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) groups showed a significantly higher plasma EREG level (1014 ± 733.9 pg/ml, 700.2 ± 676.6 pg/ml, respectively) than the healthy controls (277 ± 105.4 pg/ml). The rs2367707 polymorphism was associated with a higher risk of PTB and EPTB (P = 0.00051, P = 0.0012). Analyses of haplotype frequencies found that people with the haplotype CACAT had a higher risk of PTB and EPTB (P = 0.00031, OR = 1.43; P = 0.000053, OR = 1.65). Moreover, the rs6446993 polymorphism of the EREG gene was found to be associated with EPTB (P = 0.00087, OR = 1.54; 95% CI = 1.23-1.94). CONCLUSIONS: Compared to that of healthy controls, the level of EREG in the plasma of TB patients increased significantly. Based on these data, we demonstrated that EREG polymorphisms are genetic factors for susceptibility to TB and various forms of TB.
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Epirregulina/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Tuberculosis/genética , Adolescente , Adulto , Alelos , Estudios de Casos y Controles , Niño , China , Progresión de la Enfermedad , Epirregulina/sangre , Epirregulina/inmunología , Femenino , Genotipo , Haplotipos , Humanos , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/inmunología , Tuberculosis Pulmonar/genética , Adulto JovenRESUMEN
PURPOSE: A systematic review and meta-analysis was performed to assess the risk of congenital heart defects (CHDs) and its specific phenotypes associated with maternal diabetes mellitus (DM) including pregestational diabetes mellitus (PGDM) and gestational diabetes mellitus (GDM). METHODS: PubMed, Embase, Medline, Google Scholar, Cochrane Libraries, China National Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journals Fulltext Database and China Biology Medicine disc were searched from the inception dates to 15 December 2018, to identify case-control or cohort studies assessing the association between maternal DM and risk of CHDs. The exposure of interest was maternal DM; the outcomes of interest were CHDs and its specific phenotypes. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. Subgroup analyses were performed to explore potential heterogeneity moderators. RESULTS: Total 52 studies, which involved 259,917 patients with CHDs among 16,929,835 participants, were included for analysis. Overall, mothers with DM compared with those without DM had a significantly higher risk of CHDs in offspring [odds ratios (OR) = 2.71, 95% confidence intervals (CI) 2.28-3.23]. When data were restricted to different types of DM, a significantly increased risk of CHDs was observed among mothers with PGDM (OR = 3.18, 95% CI 2.77-3.65) and GDM (OR = 1.98, 95% CI 1.66-2.36). Our study suggested the risk of CHDs was significantly higher among mothers with PGDM than those with GDM. Additionally, this study suggested maternal DM was significantly associated with most phenotypes of CHDs; of these, double outlet of the right ventricle (OR = 10.89; 95% CI 8.77-13.53), atrioventricular septal defect (OR = 5.74; 95% CI 3.20-10.27) and truncus arteriosus (OR = 5.06; 95% CI 2.65-9.65) were identified as the first three of the most common phenotypes of CHDs associated with maternal DM. CONCLUSIONS: The maternal DM including PGDM and GDM are significantly associated with risk of CHDs and its most phenotypes. The PGDM seems to be more likely to cause CHDs in offspring than GDM. Further studies are needed to clarify the underlying mechanisms.
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Complicaciones de la Diabetes , Cardiopatías Congénitas/epidemiología , Adulto , Estudios de Casos y Controles , China , Estudios de Cohortes , Diabetes Gestacional , Femenino , Cardiopatías Congénitas/complicaciones , Humanos , Oportunidad Relativa , Embarazo , Medición de Riesgo , Factores de RiesgoRESUMEN
Interstitial leukocyte migration plays a critical role in inflammation and offers a therapeutic target for treating inflammation-associated diseases such as multiple sclerosis. Identifying small molecules to inhibit undesired leukocyte migration provides promise for the treatment of these disorders. In this study, we identified vibsanin B, a novel macrocyclic diterpenoid isolated from Viburnum odoratissimum Ker-Gawl, that inhibited zebrafish interstitial leukocyte migration using a transgenic zebrafish line (TG:zlyz-enhanced GFP). We found that vibsanin B preferentially binds to heat shock protein (HSP)90ß. At the molecular level, inactivation of HSP90 can mimic vibsanin B's effect of inhibiting interstitial leukocyte migration. Furthermore, we demonstrated that vibsanin B ameliorates experimental autoimmune encephalomyelitis in mice with pathological manifestation of decreased leukocyte infiltration into their CNS. In summary, vibsanin B is a novel lead compound that preferentially targets HSP90ß and inhibits interstitial leukocyte migration, offering a promising drug lead for treating inflammation-associated diseases.
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Movimiento Celular/efectos de los fármacos , Diterpenos/farmacología , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/metabolismo , Proteínas HSP90 de Choque Térmico/metabolismo , Leucocitos/efectos de los fármacos , Leucocitos/inmunología , Animales , Línea Celular , Sistema Nervioso Central/efectos de los fármacos , Sistema Nervioso Central/inmunología , Sistema Nervioso Central/metabolismo , Sistema Nervioso Central/patología , Diterpenos/administración & dosificación , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/patología , Femenino , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Humanos , Leucocitos/metabolismo , Ratones , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Médula Espinal/efectos de los fármacos , Médula Espinal/inmunología , Médula Espinal/metabolismo , Médula Espinal/patología , Pez CebraRESUMEN
Chitin is an important structural polysaccharide of fungal cell wall. In this paper, aerial hyphae of Colletotrichum camelliae Massee was first studied by confocal Raman microscopy in vivo. Firstly, the optimal experimental parameters of hyphae for collecting the Raman spectra were determined, and the typical Raman spectra of hyphae, chitin standard and background were acquired. By comparing analysis, characteristic peaks of chitin were found in hyphae. Then, a region of interesting on hyphae was selected for Raman scanning. Through principal component analysis, the Raman signal of hyphae and background in the scanning area can be separated clearly. Combined with loading weight plot, two main characteristic peaks of hyphae were obtained, 1 622 cm(-1) was belong to chitin and 1 368 cm(-1) was assigned to pectic polysaccharide. Finally, two and three dimension chemical images of fungal hyphae were realized based on Raman fingerprint spectra of chitin in a nondestructive way.
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Quitina/análisis , Colletotrichum/química , Hifa/química , Microscopía ConfocalRESUMEN
BACKGROUND: Leptin has been identified as an important protein involved in obesity. As a chronic metabolic disorder, obesity is associated with a high risk of developing cardiovascular and metabolic diseases, including heart failure. The aim of this paper was to investigate the effects and the mechanism of leptin on the contractile function of cardiomyocytes in the adult rat. METHODS: Isolated adult rat cardiomyocytes were exposed to leptin (1, 10, and 100 nmol/L) for 1 hour. The calcium transients and the contraction of adult rat cardiomyocytes were recorded with SoftEdge MyoCam system. Apocynin, tempol and rapamycin were added respectively, and Western blotting was employed to evaluate the expression of LC3B and Beclin-1. RESULTS: The peak shortening and maximal velocity of shortening/relengthening (± dL/dtmax) of cell shortening were significantly decreased, and the time to 50% relengthening was prolonged with leptin perfusion. Leptin also significantly reduced the baseline, peak and time to 50% baseline of calcium transient. Leptin attenuated autophagy as indicated by decreased LC3-II and Beclin-1. All of the abnormalities were significantly attenuated by apocynin, tempol or rapamycin. CONCLUSIONS: Our results indicated that leptin depressed the intracellular free calcium and myocardial systolic function via increasing oxidative stress and inhibiting autophagy.
RESUMEN
Syzygium aromaticum has been widely used in traditional medicine. Our study investigated the safety and antidepressant-like effects of the essential oil of S. aromaticum after acute or long-term treatment. Using GC-MS, a total of eight volatile constituents were identified in the essential oil of S. aromaticum. The single LD50 was approximately 4500 mg/kg based on a 24-h acute oral toxicity study. In a long-term repeated toxicity study of this essential oil (100, 200, and 400 mg/kg, p.âo.), only 400 mg/kg induced a significant decrease in body weight. In addition, no significant changes in relative organ weights and histopathological analysis were observed in all doses of essential oil-treated mice compared with the control group. Furthermore, acute S. aromaticum essential oil administration by gavage exerted antidepressant-like effects in the forced swimming test (200 mg/kg, p < 0.05) and tail suspension test (100 and 200 mg/kg, p < 0.05). Long-term S. aromaticum essential oil treatment via gavage significantly increased sucrose preference (50 mg/kg, p < 0.05; 100 and 200 mg/kg, p < 0.01) as well as elevated the protein levels of hippocampal p-ERK, p-CREB, and brain-derived neurotrophic factor in mice exposed to chronic unpredictable mild stress. These results confirmed the safety of the essential oil of S. aromaticum and suggested that its potent antidepressant-like property might be attributed to the improvement in the hippocampal pERK1/2-pCREB-BDNF pathway in rats exposed to chronic unpredictable mild stress.
Asunto(s)
Antidepresivos/uso terapéutico , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Hipocampo/metabolismo , Aceites Volátiles/uso terapéutico , Fitoterapia , Estrés Psicológico/tratamiento farmacológico , Syzygium/química , Animales , Antidepresivos/farmacología , Proteína de Unión a CREB , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Preferencias Alimentarias , Suspensión Trasera , Masculino , Ratones Endogámicos ICR , Aceites Volátiles/química , Aceites Volátiles/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratas Sprague-Dawley , Sacarosa/administración & dosificación , NataciónRESUMEN
Neurotrophic factors are well-known to be involved in the pathophysiology of depression and treatment of antidepressants. Brain-derived neurotrophic factor (BDNF), one of the most widely distributed and the most highly studied neurotrophic factors, has been demonstrated to play an important role in the pathophysiology of depression and the mechanism of antidepressants. According to the previous studies, we found that animal tissues were dissected for BDNF measurement mainly in daytime. Considering the circadian rhythm of BDNF expression, our present study evaluated the circadian variations in behaviors, serum corticosterone concentrations, hippocampal BDNF expression and neuronal cell proliferation in mice exposed to chronic mild stress (CMS), one of the most widely used depression-like animal models. Our results provided the first evidence that the difference of BDNF expression and neuronal cell proliferation between CMS and control mice underwent an oscillation related to the circadian variations (maximum at 20:00 h, minimum at 12:00 h or 16:00 h), while the difference of sucrose preference and first feeding latency was not affected by circadian rhythm. This oscillation difference was attributed to the relative constant BDNF expression and cell proliferation in CMS mice and the fluctuating BDNF expression and cell proliferation in control mice. CMS exposure might destroy the circadian rhythm of BDNF expression and cell proliferation in hippocampus of normal individual. Our present study suggests that animal decapitation at 20:00 h is the best time for BDNF-related measurement in CMS experiment, since the difference reaches the maximum.
Asunto(s)
Conducta Animal , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Proliferación Celular , Ritmo Circadiano , Depresión/metabolismo , Depresión/psicología , Anhedonia , Animales , Peso Corporal , Corticosterona/sangre , Hipocampo/metabolismo , Masculino , Ratones , Ratones Endogámicos ICR , Neuronas , Estrés Psicológico/metabolismo , Estrés Psicológico/psicología , SacarosaRESUMEN
NaOH pretreatment is a convenient and effective method which is widely used in rice straw anaerobic digestion. But the mechanism of the alkaline (NaOH) hydrolysis of biopolymers compositions and polymeric cross-linked network structures of rice straw cell wall need further study. This paper firstly studied the effect and mechanism of alkali pretreatment on anaerobic digestion and biogas production of rice straw by using a combination of confocal Raman microscopy and transmission electron microscope. First, the original rice straw and the rice straw pretreated by NaOH were taken for mapping scanning by confocal Raman microscopy with micron-scale spatial resolution. Then principal component analysis was adopted to extract main information of Raman spectra, it could be found that the two types of samples were respectively presented with ray-like distribution in the first two principal component space, which were with cumulative contribution of 99%. And there was a clear boundary between the two types of samples without any overlapping, indicating that there was a significant difference of Raman spectral characteristic between original rice leaf and rice leaf pretreated by NaOH. Further analysis of the loading weights of the first two principal components showed that the Raman peaks at 1 739, 1 508 and 1 094 cm(-1) were the important bands, and these three Raman peaks were attributed to the scattering of hemicellulose, cellulose and lignin respectively. Following, chemical imaging analysis of hemicellulose, cellulose and lignin were achieved by combining these Raman peaks and microscopic image information. It could be found that the NaOH pretreatment resulted in a loss of dense spatial uniformity structure of tissue and great decreases of the contents of these three ingredients, particularly lignin. It can be concluded that it is feasible to non-destructively measure hemicellulose, lignin and cellulose in rice straw tissue by confocal Raman microscopy, and to achieve chemical imaging analysis of the three ingredients in tissue, and this research will be much help for revealing the promotion mechanism of NaOH pretreatment for the rice straw fermentation and biogas production.
Asunto(s)
Álcalis , Oryza , Tallos de la Planta , Pared Celular/química , Celulosa , Fermentación , Hidrólisis , Lignina , Microscopía Confocal , Microscopía Electrónica de Transmisión , PolisacáridosRESUMEN
BACKGROUND: Although previous study has demonstrated that brain-derived neurotrophic factor (BDNF) is involved in the antidepressant-like effect of oleanolic acid, there is little information regarding the details of the molecular mechanism involved in this effect. METHODS: We used a chronic unpredictable mild stress (CUMS) model to test the antidepressant-like effect of oleanolic acid on depressant-like behaviour, miR-132 expression and synaptic protein expression in the male mouse hippocampus. Furthermore, we explored the possible signalling pathways associated with miR-132 expression that mediate the effect of oleanolic acid on neuronal proliferation. RESULTS: The results demonstrated that a 3-week treatment with oleanolic acid ameliorated CUMS-induced anhedonic and anxiogenic behaviours. Furthermore, we found that oleanolic acid led to the BDNF-related phosphorylation and activation of extracellular signal-regulated kinases (ERK) and cyclic adenosine monophosphate response element binding protein (CREB), which was associated with the upregulation of miR-132 and hippocampal neuronal proliferation. Moreover, experiments with an miR-132 antagomir revealed that targeting miR-132 led to inhibition of neuronal proliferation and the postsynaptic density protein 95, but did not affect presynaptic protein synapsin I. LIMITATIONS: Several other stimuli can also induce CREB phosphorylation in the hippocampus. Thus, regulation of miR-132 may not be restricted to neurotrophic signalling. CONCLUSION: Our results show that oleanolic acid induces the upregulation of miR-132, which serves as an important regulator of neurotrophic actions, mainly through the activation of the hippocampal BDNF-ERK-CREB signalling pathways.
Asunto(s)
Antidepresivos/farmacología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , MicroARNs/metabolismo , Ácido Oleanólico/farmacología , Animales , Enfermedad Crónica , Trastorno Depresivo/tratamiento farmacológico , Trastorno Depresivo/fisiopatología , Modelos Animales de Enfermedad , Homólogo 4 de la Proteína Discs Large , Guanilato-Quinasas/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/fisiopatología , Masculino , Proteínas de la Membrana/metabolismo , Ratones Endogámicos ICR , Neurogénesis/efectos de los fármacos , Neurogénesis/fisiología , Neuronas/efectos de los fármacos , Neuronas/fisiología , Distribución Aleatoria , Transducción de Señal/efectos de los fármacos , Estrés Psicológico , Incertidumbre , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Healthy tea and tea infected by anthracnose were first studied by confocal Raman microscopy to illustrate chemical changes of cell wall in the present paper. Firstly, Raman spectra of both healthy and infected sample tissues were collected with spatial resolution at micron-level, and ultrastructure of healthy and infected tea cells was got from scanning electron microscope. These results showed that there were significant changes in Raman shift and Raman intensity between healthy and infected cell walls, indicating that great differences occurred in chemical compositions of cell walls between healthy and infected samples. In details, intensities at many Raman bands which were closely associated with cellulose, pectin, esters were reduced after infection, revealing that the content of chemical compounds such as cellulose, pectin, esters was decreased after infection. Subsequently, chemical imaging of both healthy and infected tea cell walls were realized based on Raman fingerprint spectra of cellulose and microscopic spatial structure. It was found that not only the content of cellulose was reduced greatly after infection, but also the ordered structure of cellulose was destroyed by anthracnose infection. Thus, confocal Raman microscopy was shown to be a powerful tool to detect the chemical changes in cell wall of tea caused by anthracnose without any chemical treatment or staining. This research firstly applied confocal Raman microscopy in phytopathology for the study of interactive relationship between host and pathogen, and it will also open a new way for intensive study of host-pathogen at cellular level.