RESUMEN
An investigation of the chemical composition of a Formosan soft coral Cespitularia sp. led to the discovery of one new verticillene-type diterpenoid, cespitulactam M (1); one new eudesmane sesquiterpenoid, cespilamide F (2); and three new hydroperoxysteroids (3-5) along with twelve known analogous metabolites (6-17). In addition, one new derivative, cespitulactam M-6,2'-diacetate (1a), was prepared from compound 1. The structures were determined by detailed spectroscopic analyses, particularly HRESIMS and NMR techniques. Moreover, the in vitro cytotoxicity, anti-inflammatory, and antibacterial activity of 1-17 and 1a were evaluated.
Asunto(s)
Antozoos , Diterpenos , Sesquiterpenos de Eudesmano , Sesquiterpenos , Animales , Antozoos/química , Sesquiterpenos de Eudesmano/química , Espectroscopía de Resonancia Magnética , Diterpenos/química , Sesquiterpenos/química , Estructura MolecularRESUMEN
OBJECTIVE: The purpose of this study was to explore the effect of WeChat-based remote follow-up management on reducing the home care burden and anxiety of parents of premature infants. METHODS: A randomized controlled study was conducted in our hospital, with 150 premature infants enrolled in this study, each with 75 cases in the intervention group and the control group. WeChat-based remote follow-up management was performed in the intervention group after discharge, while traditional outpatient follow-up management was performed in the control group. Zarit Burden Interview (ZBI) scale as the primary outcome was used to compare the parental care burden between the two groups. RESULTS: At the 1-month follow-up, the ZBI (37.1 ± 8.3 vs. 54.2 ± 10.5 [mean ± SD], mean difference: 17.1, the 95% confidence interval for the mean difference: [14.07, 20.13], P = 0.016), Family Caregiver Task Inventory (FCTI) scale (23.1 ± 5.2 vs. 33.4 ± 6.7 [mean ± SD], mean difference: 10.3, the 95% confidence interval for the mean difference: [8.38, 12.22], P = 0.023), Self-Rating Anxiety Scale (SAS) (49.6 ± 8.5 vs. 60.2 ± 10.8 [mean ± SD], mean difference: 10.6, the 95% confidence interval for the mean difference: [7.49,13.71], P = 0.021) and Self-Rating Depression Scale (SDS) (48.2 ± 9.5 vs. 58.8 ± 11.2 [mean ± SD], mean difference: 10.6, the 95% confidence interval for the mean difference: [7.28, 13.92], P = 0.019) scores of the intervention group were lower than those of the control group, and the lower scores indicate better outcomes. CONCLUSION: WeChat-based remote follow-up management of premature infants after discharge can effectively improve parents' ability to care and their psychological state and reduce burden of care.
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Ansiedad , Carga del Cuidador , Ansiedad/psicología , Ansiedad/terapia , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Padres/psicologíaRESUMEN
MAIN CONCLUSION: We discovered and identified a series of characteristic substances, including one new polyketide, epicorepoxydon B, of the important pathogenic fungus, Epicoccum sorghinum, of sorghum. The fungal extract and some isolated polyketides are sensitive to a malignant triple-negative breast cancer cell line, MDA-MB-231. Sorghum (Kaoliang) grain is an important crop with high economic value and several applications. In Taiwan, sorghum has been used in the wine industry, and "Kinmen Kaoliang Liquor" is a well-known Asian brand. Fungal contamination is one of the major threats affecting the production of sorghum grain resulting in economic losses as well as human and animal health problems. Several fungal species can infect sorghum grain and generate some toxic secondary metabolites. Epicoccum sorghinum is one of the major fungal contaminants of sorghum grains and a potent producer of mycotoxins such as tenuazonic acid (TeA). However, except for TeA, few studies focused on chemical compounds produced by this fungus. To explore the potential biological and toxic effects of E. sorghinum, a chemical investigation was carried out on the ethyl acetate extract of the fungus because it showed cytotoxic activity against a triple-negative breast cancer cell line, MDA-MB-231 (54.82% inhibition at 20 µg/mL). One new polyketide, epicorepoxydon B (1), along with six known compounds including 4,5-dihydroxy-6-(6'-methylsalicyloxy)-2-hydroxymethyl-2-cyclohexenl-one (2), epicorepoxydon A (3), 3-hydroxybenzyl alcohol (4), 6-methylsalicylic acid (5), gentisyl alcohol (6), and 6-(hydroxymethyl)benzene-1,2,4-triol (7) were obtained, and their structures were established by the interpretation of their MS and NMR spectroscopic data. The cytotoxic activity of all isolated polyketides 1-7 was evaluated, and compounds 2, 6, and 7 exhibited potent activities against A549, HepG2, and MDA-MB-231 human cancer cell lines with IC50 value ranging from 1.86 to 18.31 µM. The structure-activity relationship of the isolated compounds was proposed.
Asunto(s)
Ascomicetos , Policétidos , Sorghum , Grano Comestible , Estructura MolecularRESUMEN
Cupressus macrocarpa is a windbreak tree and is reported to have various cytotoxic effects. A natural product study on the leaves of C. macrocarpa has yielded ten secondary metabolites, including three new diterpenoids (1-3), four known diterpenoids (4-7), and three known lignans (8-10). The structures of all isolated compounds were elucidated via the interpretation of spectroscopic methods, especially 2D NMR and mass analyses. In the cytotoxic assays, compounds 1-3 and 7-10 showed inhibition effect against HepG2, MDA-MB-231, and A549 cells with IC50 values ranging from 0.004 to 19.9 µg/mL. Moreover, the anti-inflammatory assays revealed that (-)-matairesinol (8) had significant inhibitory activities on superoxide anion generation (IC50 = 2.7 ± 0.3 µM) and elastase release (IC50 = 6.6 ± 0.7 µM).
Asunto(s)
Antiinflamatorios/química , Cupressus/química , Diterpenos/química , Lignanos/química , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Cupressus/metabolismo , Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Humanos , Lignanos/aislamiento & purificación , Lignanos/farmacología , Espectroscopía de Resonancia Magnética , Conformación Molecular , Neutrófilos/citología , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Elastasa Pancreática/metabolismo , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Superóxidos/metabolismoRESUMEN
Lysinuric protein intolerance (LPI) is an autosomal recessive disorder caused by SLC7A7 gene mutation and often involves severe lesions in multiple systems. Lung involvement is frequently seen in children with LPI and such children tend to have a poor prognosis. This article summarizes the clinical manifestations and gene mutation characteristics of three children diagnosed with LPI by SLC7A7 gene analysis. All three children had the manifestations of aversion to protein-rich food after weaning, delayed development, anemia, hepatosplenomegaly, and osteoporosis, as well as an increase in orotic acid in urine. In addition, interstitial pneumonia and diffuse pulmonary interstitial lesions were observed in two children. SLC7A7 gene detection showed three pathogenic mutations in these children, namely c.1387delG(p.V463CfsX56), c.1215G>A(p.W405X) and homozygous c.625+1G>A. After a definite diagnosis was made, all three children were given a low-protein diet and oral administration of citrulline [100 mg/(kg.d)], iron protein succinylate [4 mg/(kg.d)], calcium and zinc gluconates oral solution (10â mL/day) and vitamin D (400â IU/day). In addition, patient 3 was given prednisone acetate (5â mg/day). The children had varying degrees of improvement in symptoms and signs. It is hard to distinguish LPI from urea cycle disorder due to the features of amino acid and organic acid metabolism in LPI, and SLC7A7 gene analysis is the basis for a definite diagnosis of LPI.
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Errores Innatos del Metabolismo de los Aminoácidos , Cadenas Ligeras de la Proteína-1 Reguladora de Fusión/genética , Errores Innatos del Metabolismo de los Aminoácidos/genética , Sistema de Transporte de Aminoácidos y+L , Niño , Citrulina , Humanos , Lisina , MutaciónRESUMEN
Five new compounds named buxifoximes A-C (1-3), buxifobenzoate (4), and 7- O-(7'-peroxygeranyl) coumarin (5), together with 25 known compounds, were identified from the twigs of Atalantia buxifolia. Compounds 1-3 are unique secondary metabolites with the aldoxime functionality. The structures of the isolates were determined on the basis of spectroscopic data analyses, and the structure of 1 was confirmed by an X-ray single-crystallographic analysis. With respect to bioactivity, antidengue virus, anti-inflammatory, and cytotoxic activities of all purified compounds were tested and evaluated. Compound 1 showed a significant anti-inflammatory effect by inhibiting superoxide anion generation with an IC50 value of 4.8 ± 0.7 µM. Among the acridone alkaloids, 5-hydroxy- N-methylseverifoline (23) exhibited antidengue activity (IC50 = 5.3 ± 0.4 µM), and atalaphyllinine (20) demonstrated cytotoxicity (IC50 = 6.5 ± 0.0 µM) against the human liver cancer cell line, HepG2.
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Fenoles/aislamiento & purificación , Rutaceae/química , Antiinflamatorios no Esteroideos/aislamiento & purificación , Antiinflamatorios no Esteroideos/farmacología , Antivirales/aislamiento & purificación , Antivirales/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Células Hep G2 , Humanos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Fenoles/química , Fenoles/farmacologíaRESUMEN
The tree Aquilaria malaccensis is a valuable source of agarwood, which is used in herbal medicinal preparations. Phytochemical research on A. malaccensis seeds has led to the isolation of four new phorbol esters (1-4), two known phorbol esters (5, isolated from Nature for the first time, and 6), and two known glycerides (7 and 8). The structures of these isolates were elucidated by means of spectroscopic data interpretation. The inflammation-modulatory activities of the isolates on elastase release and superoxide anion generation in human neutrophils were evaluated. Interestingly, phorbol esters 1, 5, and 6 showed potent inhibitory activity on elastase release in human neutrophils, with IC50 values of 2.7, 0.8, and 2.1 µM, respectively. All isolated phorbol esters exerted enhancing activity on superoxide anion generation. The results indicated that phorbol esters may play a bilateral modulatory role in the processes of inflammation. In addition, the compounds were evaluated for their cytotoxic properties against HepG2 (hepatoma), MDA-MB-231 (breast), and A549 (lung) cancer cells, but all compounds were inactive for all cell lines used (IC50 > 10 µM).
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Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Glicéridos/aislamiento & purificación , Glicéridos/farmacología , Neutrófilos/efectos de los fármacos , Ésteres del Forbol/aislamiento & purificación , Ésteres del Forbol/farmacología , Semillas/química , Thymelaeaceae/química , Antiinflamatorios/química , Glicéridos/química , Humanos , Estructura Molecular , Neutrófilos/química , Ésteres del Forbol/químicaRESUMEN
OBJECTIVE: To investigate the value of combined determination of neutrophil CD64 and procalcitonin (PCT) in the early diagnosis of neonatal bacterial infection. METHODS: According to discharge diagnosis, 37 neonates with bacterial infection were divided into sepsis (n=15) and ordinary infection (non-sepsis) groups (n=22). Twenty-one neonates without infection who were hospitalized during the same period of time were enrolled as the control group. Venous blood samples were collected immediately after admission. Flow cytometry was used to measure the serum level of neutrophil CD64. Chemiluminescence and immune transmission turbidimetry were used to measure the serum levels of PCT and CRP respectively. RESULTS: The sepsis group had higher serum levels of neutrophil CD64, PCT, and CRP than the control group (P<0.01), the ordinary infection group had a higher serum level of neutrophil CD64 than the control group (P<0.01), and the sepsis group had higher serum levels of PCT and CRP than the ordinary infection group (P<0.01). The areas under the ROC curve (AUC) of neutrophil CD64, PCT, and CRP in diagnosing bacterial infection were 0.818, 0.818, and 0.704 respectively, and the AUC of combined neutrophil CD64 and PCT was 0.926. A combination of neutrophil CD64 and PCT had a sensitivity of 97.29% and an accuracy of 89.65% in the early diagnosis of neonatal bacterial infection.The sensitivity and accuracy were higher than those of a combination of CRP and neutrophil CD64 or PCT as well as neutrophil CD64, PCT, or CRP alone for the early diagnosis of neonatal bacterial infection. CONCLUSIONS: The combined determination of neutrophil CD64 and PCT can improve the sensitivity and accuracy in the diagnosis of neonatal bacterial infection, which helps with early identification of bacterial infection.
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Infecciones Bacterianas/diagnóstico , Calcitonina/sangre , Neutrófilos/química , Receptores de IgG/sangre , Infecciones Bacterianas/sangre , Proteína C-Reactiva/análisis , Diagnóstico Precoz , Femenino , Humanos , Recién Nacido , Masculino , Curva ROCRESUMEN
Parvistones A-E (1-5), five new styryllactones possessing a rare α,ß-lactone moiety and a 6S configuration, were isolated from a methanolic extract of Polyalthia parviflora leaves. The structures and the absolute configuration of the isolates were elucidated using NMR spectroscopy, specific rotation, circular dichroism, and X-ray single-crystal analysis. Compounds 8, 9, 11, and 12 were isolated for the first time. The results were supported by comparing the data measured to those of 6R-styryllactones. Moreover, a plausible biogenetic pathway of the isolated compounds was proposed. The structure-activity relationship of the compounds in an in vitro anti-inflammatory assay revealed the 6S-styryllactones to be more potent than the 6R derivatives. However, the effect was opposite regarding their cytotoxic activity. In addition, 6S-styrylpyrones isolated showed more potent anti-inflammatory and cytotoxic activity when compared to the 1S-phenylpyranopyrones obtained.
Asunto(s)
Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Lactonas/aislamiento & purificación , Lactonas/farmacología , Polyalthia/química , Antiinflamatorios/química , Dicroismo Circular , Cristalografía por Rayos X , Lactonas/química , Conformación Molecular , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Hojas de la Planta/química , Estereoisomerismo , Relación Estructura-Actividad , VietnamRESUMEN
A new chromene derivative, 2-(4',8'-dimethylnona-3'E,7'-dienyl)-8-hydroxy-2,6-dimethyl-2H-chromene (1) together with four known natural products, methylfarnesylquinone (2), isololiolide (3), pheophytin a (4), and ß-carotene (5) were isolated from the brown alga Homoeostrichus formosana. The structure of 1 was determined by extensive 1D and 2D spectroscopic analyses. Acetylation of 1 yielded the monoacetylated derivative 2-(4',8'-dimethylnona-3'E,7'-dienyl)-8-acetyl-2,6-dimethyl-2H-chromene (6). Compounds 1-6 exhibited various levels of cytotoxic, antibacterial, and anti-inflammatory activities. Compound 2 was found to display potent in vitro anti-inflammatory activity by inhibiting the generation of superoxide anion (IC50 0.22 ± 0.03 µg/mL) and elastase release (IC50 0.48 ± 0.11 µg/mL) in FMLP/CB-induced human neutrophils.
Asunto(s)
Antiinflamatorios/química , Benzopiranos/química , Benzoquinonas/química , Phaeophyceae/química , Antibacterianos/química , Antibacterianos/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/toxicidad , Benzopiranos/farmacología , Benzopiranos/toxicidad , Benzoquinonas/farmacología , Benzoquinonas/toxicidad , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Células Hep G2 , Humanos , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Conformación Molecular , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Phaeophyceae/metabolismo , Superóxidos/metabolismoRESUMEN
Bioassay-guided fractionation of the CHCl3 layer of Solanum violaceum areal parts methanolic extract led to the isolation of four new steroidal sapogenins, indiosides L-O (1-4), along with eight known steroids, one lignin, and a coumarin. Indioside L is a rare spirostanoid possessing a 1,4-dien-3-one moiety in ring A. Moreover, compounds 3 and 4 represent rare examples of spirostene with the 3ß,7α-diol-5,6-ene moiety compared to the normal 3ß,7ß-diol-5,6-ene derivatives. The cytotoxic activity of the isolates (5-14) was evaluated against human hepatoma (HepG2 and Hep3B), human lung carcinoma (A549), and human breast carcinoma (MDA-MB-231 and MCF-7).
Asunto(s)
Antineoplásicos/química , Solanum/química , Espirostanos/química , Antineoplásicos/aislamiento & purificación , Antineoplásicos/toxicidad , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Células Hep G2 , Humanos , Células MCF-7 , Espectroscopía de Resonancia Magnética , Conformación Molecular , Hojas de la Planta/química , Tallos de la Planta/química , Espirostanos/aislamiento & purificación , Espirostanos/toxicidadRESUMEN
Objective: To study the differences in blood cellular communication network factor 1 (CCN1) levels between patients with diabetes mellitus (DM) and healthy individuals and to explore the relationship between CCN1 and diabetic retinopathy (DR). Methods: Plasma CCN1 levels were detected using ELISA in 50 healthy controls, 74 patients with diabetes without diabetic retinopathy (DM group), and 69 patients with diabetic retinopathy (DR group). Correlations between CCN1 levels and age, body mass index, mean arterial pressure, hemoglobin A1c, and other factors were analyzed. The relationship between CCN1 expression and DR was explored using logistic regression after adjusting for confounding factors. Blood mRNA sequencing analysis was performed for all subjects, and the molecular changes that may be related to CCN1 were explored. The retinal vasculature of streptozotocin-induced diabetic rats was examined using fundus fluorescein angiography; in addition, retinal protein expression was examined using western blotting. Results: Plasma CCN1 levels in patients with DR were significantly higher than in the control and DM groups; however, no significant differences were observed between healthy controls and patients with DM. CCN1 levels negatively correlated with body mass index and positively correlated with the duration of diabetes and urea levels. It was observed that high (OR 4.72, 95% CI: 1.10-20.25) and very high (OR 8.54, 95% CI: 2.00-36.51) levels of CCN1 were risk factors for DR. Blood mRNA sequencing analysis revealed that CCN1-related pathways were significantly altered in the DR group. The expression of hypoxia-, oxidative stress-, and dephosphorylation-related proteins were elevated, while that of tight junction proteins were reduced in the retinas of diabetic rats. Conclusion: Blood CCN1 levels are significantly elevated in patients with DR. High and very high levels of plasma CCN1 are risk factors for DR. Blood CCN1 level may be a potential biomarker for diagnosis of DR. The effects of CCN1 on DR may be related to hypoxia, oxidative stress, and dephosphorylation.
Asunto(s)
Diabetes Mellitus Experimental , Retinopatía Diabética , Animales , Ratas , Diabetes Mellitus Experimental/metabolismo , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/etiología , Retinopatía Diabética/metabolismo , Retina/metabolismo , Factores de Riesgo , ARN Mensajero/metabolismoRESUMEN
Five new steroidal glycosides (1-5) and nine known compounds were isolated from Solanum violaceum. Indiosides G (1) and H (2) are spirostene saponins with an iso-type F ring, indioside I (3) is a spirostane saponin, and indiosides J (4) and K (5) are unusual furostanol saponins with a deformed F ring. These structures represent rare naturally occurring steroidal skeletons. The structures of the new compounds were elucidated using 1D and 2D spectroscopic techniques and acid hydrolysis. Compounds 2, 3, and 7-9 exhibited cytotoxic activity against six human cancer cell lines (HepG2, Hep3B, A549, Ca9-22, MDA-MB-231, and MCF-7) with IC(50) values of 1.83-8.04 µg/mL. Steroidal saponins 3, 8, and 9 showed inhibitory effects on superoxide anion generation with IC(50) values of 2.84 ± 0.18, 0.62 ± 0.03, and 1.62 ± 0.59 µg/mL, respectively. Saponins 8 and 9 also inhibited elastase release with IC(50) values of 111.05 ± 7.37 and 4.04 ± 0.51 µg/mL, respectively. Structure-activity relationship correlations of these compounds with respect to cytotoxic and anti-inflammatory effects are discussed.
Asunto(s)
Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Antineoplásicos/aislamiento & purificación , Antineoplásicos/farmacología , Glicósidos/aislamiento & purificación , Glicósidos/farmacología , Solanum/química , Esteroides/aislamiento & purificación , Esteroides/farmacología , Antiinflamatorios/química , Antineoplásicos/química , Ensayos de Selección de Medicamentos Antitumorales , Glicósidos/química , Humanos , Concentración 50 Inhibidora , Estructura Molecular , Neutrófilos/efectos de los fármacos , Neutrófilos/enzimología , Resonancia Magnética Nuclear Biomolecular , Esteroides/química , Relación Estructura-Actividad , TaiwánRESUMEN
OBJECTIVE: To review clinical features of four male patients with glutaric academia type I and screen glutaryl-CoA dehydrogenase (GCDH) gene mutations. METHODS: The 4 patients underwent brain computer tomography (CT) and magnetic resonance imaging (MRI) analyses. Blood acylcarnitine and urine organic acid were analyzed with tandem mass spectrometry and gas chromatographic mass spectrometry. Genomic DNA was extracted from peripheral blood samples. The 11 exons and flanking sequences of GCDH gene were amplified with PCR and subjected to direct DNA sequencing. RESULTS: All patients have manifested macrocephaly, with head circumference measured 50 cm (14 months), 47 cm (9 months), 46 cm (5 months) and 51 cm (14 months), respectively. Imaging analyses also revealed dilation of Sylvian fissure and lateral ventricles, frontotemporal atrophy, subarachnoid space enlargement and cerebellar vermis abnormalities. All patients had elevated glutarylcarnitine (5.8 umol/L, 7.5 umol/L, 8.3 umol/L and 7.9 umol/L, respectively) and high urinary excretion of glutaric acid. Seven mutations were identified among the patients, among which c.146_149del4, IVS6-4_Ex7+4del8, c.508A>G (p.K170E), c.797T>C (p.M266T) and c.420del10 were first discovered. CONCLUSION: Macrocephaly and neurological impairment are the most prominent features of glutaric academia type I. Blood tandem mass spectrometry and urine gas chromatographic mass spectrometry analysis can facilitate the diagnosis. The results can be confirmed by analysis of GCDH gene mutations.
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Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Errores Innatos del Metabolismo de los Aminoácidos/genética , Encefalopatías Metabólicas/diagnóstico , Encefalopatías Metabólicas/genética , Glutaril-CoA Deshidrogenasa/genética , Mutación , Errores Innatos del Metabolismo de los Aminoácidos/metabolismo , Secuencia de Aminoácidos , Secuencia de Bases , Encefalopatías Metabólicas/metabolismo , Glutaril-CoA Deshidrogenasa/deficiencia , Glutaril-CoA Deshidrogenasa/metabolismo , Humanos , Lactante , Masculino , Datos de Secuencia Molecular , Alineación de SecuenciaRESUMEN
OBJECTIVE: To assess the feasibility of high-resolution melting (HRM) analysis for screening patients with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). METHODS: Based on previous studies on SLC25A13 gene in Chinese patients with NICCD, four hotspot mutations (851del4, 1638ins23, IVS6+5G>A and IVS16ins3kb) were selected. Results of the HRM analysis was validated using 50 negative controls and 20 patients with NICCD whose genotypes were confirmed previously by direct sequencing. With the established protocol, 171 suspected patients were enrolled. Samples with abnormal melting curves were further validated by DNA sequencing. RESULTS: HRM analysis can accurately determine the genotypes of all negative controls and patients. The sensitivity and specificity of the technique reached 100% (70/70). The melting curves of samples with the same genotype were highly reproducible. In 171 suspected patients, seven NICCD patients were detected by HRM. Identified mutations have included one case of 851del4 homozygote, one case of IVS6+5G>A heterozygote, 3 cases of 851del4 heterozygotes, one case of [IVS6+5G>A]+[ 851del4] and one case of [1638ins23+IVS16ins3kb]+[1638ins23]. All mutations were subsequently confirmed by DNA sequencing. CONCLUSION: HRM analysis is a convenient, high-throughput and rapid technique for the screening of NICCD patients.
Asunto(s)
Proteínas de Unión al Calcio/deficiencia , Citrulinemia/diagnóstico , Citrulinemia/genética , ADN/química , Transportadores de Anión Orgánico/deficiencia , Proteínas de Transporte de Anión/genética , Secuencia de Bases , China , Citrulinemia/metabolismo , ADN/genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Proteínas Mitocondriales/genética , Datos de Secuencia Molecular , Mutación , Desnaturalización de Ácido Nucleico , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Ornithine transcarbamylase deficiency (OTCD) is an X-linked inherited disorder and characterized by marked elevation of blood ammonia. The goal of treatment is to minimize the neurological damage caused by hyperammonemia. OTCD can be cured by liver transplantation (LT). Post-transplant patients can discontinue anti- hyperammonemia agents and consume a regular diet without the risk of developing hyperammonemia. The neurological damage caused by hyperammonemia is almost irreversible. CASE SUMMARY: An 11.7-year-old boy presented with headache, vomiting, and altered consciousness. The patient was diagnosed with late-onset OTCD. After nitrogen scavenging treatment and a protein-free diet, ammonia levels were reduced to normal on the third day of admission. Nevertheless, the patient remained in a moderate coma. After discussion, LT was performed. Following LT, the patient's blood ammonia and biochemical indicators stabilized in the normal range, he regained consciousness, and his nervous system function significantly recovered. Two months after LT, blood amino acids and urine organic acids were normal, and brain magnetic resonance imaging showed a decrease in subcortical lesions. CONCLUSION: LT can significantly improve partial neurological impairment caused by late-onset OTCD hyperammonemic encephalopathy, and LT can be actively considered when early drug therapy is ineffective.
RESUMEN
One new phenanthrenedione, pterolinus K (1), and one new chalcone, pterolinus L (2) were isolated from the heartwood extract of Pterocarpus santalinus. The structures were elucidated by spectroscopic methods. Both 1 and 2 showed inhibitory effect on elastase release by human neutrophils in response to fMLP with an IC(50) value of 4.24 and 0.95 µM, and compound 1 also inhibited superoxide anion generation with IC(50) value of 0.99 µM. In addition, compound 1 showed selective cytotoxicity against HepG2 with IC(50) value of 10.86 µM, while compound 2 showed a moderate cytotoxicity against KB with IC(50) values of 17.18 µM.
Asunto(s)
Antineoplásicos/farmacología , Chalconas/farmacología , Inhibidores Enzimáticos/farmacología , Elastasa Pancreática/antagonistas & inhibidores , Fenantrenos/farmacología , Extractos Vegetales/farmacología , Pterocarpus/química , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , Chalconas/química , Chalconas/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Células Hep G2 , Humanos , Células KB , Estructura Molecular , N-Formilmetionina Leucil-Fenilalanina/farmacología , Neutrófilos/enzimología , Elastasa Pancreática/metabolismo , Fenantrenos/química , Fenantrenos/aislamiento & purificación , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Estereoisomerismo , Relación Estructura-Actividad , Superóxidos/antagonistas & inhibidores , Superóxidos/metabolismoRESUMEN
Five new benzofurans, pterolinuses A-E (1-5), six new neoflavonoids, pterolinuses F-J (8-13), and five known compounds (6, 7, 14-16) were isolated from an extract of Pterocarpus santalinus heartwood. All new structures were elucidated by spectroscopic methods, and configurations were confirmed by CD spectral data and optical rotation values. The isolates were evaluated for anti-inflammatory and cytotoxic activities. Six compounds (1, 2, 4, 6, 7, and 15) showed significant inhibition in at least one anti-inflammatory assay. Compound 2 showed the best selective effect against superoxide anion generation in human neutrophils with, an IC50 value of 0.19 µg/mL, and was 6.2-fold more potent than the positive control LY294002. Compound 14 showed the highest cytotoxicity against Ca9-22 cancer cells, with an IC50 value of 0.46 µg/mL.
Asunto(s)
Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Benzofuranos/aislamiento & purificación , Benzofuranos/farmacología , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Plantas Medicinales/química , Pterocarpus/química , Antiinflamatorios/química , Benzofuranos/química , Cromonas/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Flavonoides/química , Humanos , India , Concentración 50 Inhibidora , Estructura Molecular , Morfolinas/farmacología , Neutrófilos/efectos de los fármacos , Superóxidos/antagonistas & inhibidoresRESUMEN
OBJECTIVE: Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) which resulted from mutation in SLC25A13 gene can present transient intrahepatic cholestasis, low birth weight, growth retardation, hypoproteinemia and so on. This study aimed to identify the mutation type of NICCD patients by DNA sequencing. METHODS: Twenty children diagnosed as NICCD were consented to enroll in this study. PCR assays were performed to amplify the eighteen exons and its flanking sequences of SLC25A13 gene, which were defined as the upstream and downstream 50 bp from starting and ending site of the exons. Then the PCR products were purified and followed by automated DNA sequencing. The IVS16ins3kb mutation was detected by nested PCR and RT-PCR. RESULTS: Seven genetic variations of SLC25A13, termed as 851del4, 1638ins23, IVS16ins3kb, IVS6+5G>A, c.775C>T (p.Q259X), c.1505C>T (p.P502L) and c.1311C>T (p.C437C), were identified in the subjects, of which c.775C>T (p.Q259X), c.1505C>T (p.P502L) and c.1311C>T (p.C437C) were reported for the first time in NICCD patients. And a compound mutation ofï¼»1638ins23+IVS16ins3kbï¼½was also identified. In 20 patients with NICCD, 6 patients were 851del4 homozygotes, 7 patients were compound heterozygotes, and 7 patients were heterozygotes of single mutation. 851del4 was the major mutation type (64%), followed by 1638ins23 (15%), IVS16ins3kb (12%) and IVS6+5G>A (6%). CONCLUSIONS: 851del4 is the major mutation type in Chinese patients with NICCD.
Asunto(s)
Colestasis Intrahepática/genética , Proteínas de Transporte de Membrana Mitocondrial/genética , Mutación , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Proteínas de Transporte de Membrana Mitocondrial/deficiencia , Análisis de Secuencia de ADNRESUMEN
Exercise-induced muscle damage (EIMD) is characterized by a reduction in functional performance, disruption of muscle structure, production of reactive oxygen species, and inflammatory reactions. Ginseng, along with its major bioactive component ginsenosides, has been widely employed in traditional Chinese medicine. The protective potential of American ginseng (AG) for eccentric EIMD remains unclear. Twelve physically active males (age: 22.4 ± 1.7 years; height: 175.1 ± 5.7 cm; weight: 70.8 ± 8.0 kg; peak oxygen consumption [VËO2peak] 54.1 ± 4.3 mL/kg/min) were administrated by AG extract (1.6 g/day) or placebo (P) for 28 days and subsequently challenged by downhill (DH) running (-10% gradient and 60% VËO2peak). The levels of circulating 8-iso-prostaglandin F 2α (PGF2α), creatine kinase (CK), interleukin (IL)-1ß, IL-4, IL-10, and TNF-α, and the graphic pain rating scale (GPRS) were measured before and after supplementation and DH running. The results showed that the increases in plasma CK activity induced by DH running were eliminated by AG supplementation at 48 and 72 h after DH running. The level of plasma 8-iso-PGF2α was attenuated by AG supplementation immediately (p = 0.01 and r = 0.53), 2 h (p = 0.01 and r = 0.53) and 24 h (p = 0.028 and r = 0.45) after DH running compared with that by P supplementation. Moreover, our results showed an attenuation in the plasma IL-4 levels between AG and P supplementation before (p = 0.011 and r = 0.52) and 72 h (p = 0.028 and r = 0.45) following DH running. Our findings suggest that short-term supplementation with AG alleviates eccentric EIMD by decreasing lipid peroxidation and promoting inflammatory adaptation.