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1.
BMC Nephrol ; 25(1): 13, 2024 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-38178022

RESUMO

BACKGROUND: Combined methylmalonic acidemia (MMA) and hyperhomocysteinemia, cobalamin C (cblC) type, also named cblC deficiency is a rare autosomal recessive genetic metabolic disease. It progressively causes neurological, hematologic, renal and other system dysfunction. The clinical manifestations are relatively different due to the onset time of disease. CASE PRESENTATION: This report describes a rare case of a 26 year old man with cblC deficiency who developed life-threatening aortic dissection and acute kidney injury (AKI) and showed neuropsychiatric symptoms with elevated serum homocysteine and methylmalonic aciduria. After emergent operation and intramuscular cobalamin supplementation therapy, the male recovered from aortic dissection, neurological disorder and AKI. Finally, two previously published compound heterozygous variants, c.482G > A (p.R161Q) and c.658_660del (p.K220del) in the MMACHC gene were detected in this patient and he was confirmed to have cblC deficiency. CONCLUSIONS: Poor cognizance of presenting symptoms and biochemical features of adult onset cblC disease may cause delayed diagnosis and management. This case is the first to depict a case of adult-onset cblC deficiency with aortic dissection. This clinical finding may contribute to the diagnosis of cblC deficiency.


Assuntos
Injúria Renal Aguda , Erros Inatos do Metabolismo dos Aminoácidos , Hiper-Homocisteinemia , Adulto , Masculino , Humanos , Hiper-Homocisteinemia/complicações , Hiper-Homocisteinemia/diagnóstico , Hiper-Homocisteinemia/genética , Vitamina B 12 , Erros Inatos do Metabolismo dos Aminoácidos/complicações , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Erros Inatos do Metabolismo dos Aminoácidos/genética , Injúria Renal Aguda/etiologia , Oxirredutases
2.
J Am Chem Soc ; 145(41): 22609-22619, 2023 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-37803879

RESUMO

Cerebral ischemia-reperfusion injury (CIRI) is often accompanied by upregulation of homocysteine (Hcy). Excessive Hcy damages cerebral vascular endothelial cells and neurons, inducing neurotoxicity and even neurodegeneration. Normally, supplementation of vitamin B12 is an ideal intervention to reduce Hcy. However, vitamin B12 therapy is clinically inefficacious for CIRI. Considering oxidative stress is closely related to CIRI, the lysosome is the pivotal site for vitamin B12 transport. Lysosomal oxidative stress might hinder the transport of vitamin B12. Whether lysosomal malondialdehyde (lysosomal MDA), as the authoritative biomarker of lysosomal oxidative stress, interferes with the transport of vitamin B12 has not been elucidated. This is ascribed to the absence of effective methods for real-time and in situ measurement of lysosomal MDA within living brains. Herein, a fluorescence imaging agent, Lyso-MCBH, was constructed to specifically monitor lysosomal MDA by entering the brain and targeting the lysosome. Erupting the lysosomal MDA level in living brains of mice under CIRI was first observed using Lyso-MCBH. Excessive lysosomal MDA was found to affect the efficacy of vitamin B12 by blocking the transport of vitamin B12 from the lysosome to the cytoplasm. More importantly, the expression and function of the vitamin B12 transporter LMBD1 were proved to be associated with excessive lysosomal MDA. Altogether, the revealing of the lysosomal MDA-LMBD1 axis provides a cogent interpretation of the inefficacy of vitamin B12 in CIRI, which could be a prospective therapeutic target.


Assuntos
Isquemia Encefálica , Traumatismo por Reperfusão , Animais , Camundongos , Vitamina B 12/farmacologia , Vitamina B 12/metabolismo , Malondialdeído/metabolismo , Células Endoteliais/metabolismo , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Lisossomos/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Vitaminas/metabolismo , Homocisteína/metabolismo
3.
Molecules ; 27(24)2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36558182

RESUMO

The flower bud of Panax notoginseng (PNF) consumed as a tonic shows potential in the prevention and treatment of cardiovascular diseases. To identify the contained multi-components and, in particular, to clarify which components can be absorbed and what metabolites are transformed, unveiling the effective substances of PNF is of vital significance. A unique ultrahigh-performance liquid chromatography/ion mobility quadrupole time-of-flight mass spectrometry (UHPLC/IM-QTOF-MS) profiling approach and efficient data processing by the UNIFITM bioinformatics platform were employed to comprehensively identify the multi-components of PNF and the related metabolites in the plasma of rats after oral administration (at a dose of 3.6 g/kg). Two MS2 data acquisition modes operating in the negative electrospray ionization mode, involving high-definition MSE (HDMSE) and data-dependent acquisition (DDA), were utilized aimed to extend the coverage and simultaneously ensure the quality of the MS2 spectra. As a result, 219 components from PNF were identified or tentatively characterized, and 40 thereof could be absorbed. Moreover, 11 metabolites were characterized from the rat plasma. The metabolic pathways mainly included the phase I (deglycosylation and oxidation). To the best of our knowledge, this is the first report that systematically studies the in vivo metabolites of PNF, which can assist in better understanding its tonifying effects and benefit its further development.


Assuntos
Medicamentos de Ervas Chinesas , Panax notoginseng , Ratos , Animais , Panax notoginseng/química , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas , Plasma/química , Flores/química , Medicamentos de Ervas Chinesas/química
4.
J Asian Nat Prod Res ; 24(7): 673-678, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34308726

RESUMO

A new coumestan named 7,5'-dihydroxy-4'-(3''-hydroxy-3''-methyl-trans-isobut-1''-enyl) coumestan (1), together with five known compounds (2-6), was isolated from the EtOAc-soluble extract of the stems of Acanthopanax senticosus. Their structures were elucidated based on extensive spectroscopic analyses. All the isolates were evaluated for in vitro cytotoxic activities against four human cancer cells including HepG2, A549, HeLa and MCF-7. Among them, the new compound 1 was found to exhibit significant cytotoxic activity on HeLa cells with IC50 value of 6.5 µM.


Assuntos
Antineoplásicos , Eleutherococcus , Eleutherococcus/química , Células HeLa , Humanos , Estrutura Molecular , Extratos Vegetais/química
5.
J Neurol ; 269(6): 2980-2988, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34779889

RESUMO

OBJECTIVE: To investigate atrophy patterns in hypothalamic subunits at different stages of ALS and examine correlations between hypothalamic subunit volume and clinical information. METHODS: We used the King's clinical staging system to divide 91 consecutive ALS patients into the different disease stages. We investigated patterns of hypothalamic atrophy using a recently published automated segmentation method in ALS patients and in 97 healthy controls. We recorded all subjects' demographic and clinical information. RESULTS: Compared with healthy controls, we found significant atrophy in the bilateral anterior-superior subunit and the superior tubular subunit, as well as a reduction in global hypothalamic volume in ALS patients. When we used the King's clinical staging system to divide patients into the different disease stages, we found neither global nor specific subunit atrophy until King's stage 3 in the hypothalamus. Moreover, specific subunit volumes were significantly associated with body mass index. CONCLUSIONS: In a relatively large sample of Chinese patients with ALS, using a recently published automated segmentation method for the hypothalamus, we found the pattern of hypothalamic atrophy in ALS patients differed greatly across King's clinical disease stages. Moreover, specific hypothalamic subunit atrophy may play an important role in energy metabolism in ALS patients. Thus, our findings suggest that hypothalamic atrophy may have potential phenotypic associations, and improved energy metabolism may become an important component of individualised therapy for ALS.


Assuntos
Esclerose Lateral Amiotrófica , Esclerose Lateral Amiotrófica/diagnóstico por imagem , Atrofia , Índice de Massa Corporal , Humanos , Hipotálamo/diagnóstico por imagem
6.
Hum Mol Genet ; 31(7): 1115-1129, 2022 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-34718578

RESUMO

To observe a long-term prognosis in late-onset multiple acyl-coenzyme-A dehydrogenation deficiency (MADD) patients and to determine whether riboflavin should be administrated in the long-term and high-dosage manner, we studied the clinical, pathological and genetic features of 110 patients with late-onset MADD in a single neuromuscular center. The plasma riboflavin levels and a long-term follow-up study were performed. We showed that fluctuating proximal muscle weakness, exercise intolerance and dramatic responsiveness to riboflavin treatment were essential clinical features for all 110 MADD patients. Among them, we identified 106 cases with ETFDH variants, 1 case with FLAD1 variants and 3 cases without causal variants. On muscle pathology, fibers with cracks, atypical ragged red fibers (aRRFs) and diffuse decrease of SDH activity were the distinctive features of these MADD patients. The plasma riboflavin levels before treatment were significantly decreased in these patients as compared to healthy controls. Among 48 MADD patients with a follow-up of 6.1 years on average, 31 patients were free of muscle weakness recurrence, while 17 patients had episodes of slight muscle weakness upon riboflavin withdrawal, but recovered after retaking a small-dose of riboflavin for a short-term. Multivariate Cox regression analysis showed vegetarian diet and masseter weakness were independent risk factors for muscle weakness recurrence. In conclusion, fibers with cracks, aRRFs and diffuse decreased SDH activity could distinguish MADD from other genotypes of lipid storage myopathy. For late-onset MADD, increased fatty acid oxidation and reduced riboflavin levels can induce episodes of muscle symptoms, which can be treated by short-term and small-dose of riboflavin therapy.


Assuntos
Proteínas Ferro-Enxofre , Deficiência Múltipla de Acil Coenzima A Desidrogenase , Oxirredutases atuantes sobre Doadores de Grupo CH-NH , Acil Coenzima A/genética , Proteínas Adaptadoras de Sinalização de Receptores de Domínio de Morte/genética , Flavoproteínas Transferidoras de Elétrons/genética , Flavoproteínas Transferidoras de Elétrons/metabolismo , Seguimentos , Fatores de Troca do Nucleotídeo Guanina/genética , Humanos , Proteínas Ferro-Enxofre/genética , Deficiência Múltipla de Acil Coenzima A Desidrogenase/diagnóstico , Deficiência Múltipla de Acil Coenzima A Desidrogenase/tratamento farmacológico , Deficiência Múltipla de Acil Coenzima A Desidrogenase/genética , Debilidade Muscular/patologia , Músculo Esquelético/metabolismo , Mutação , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Estudos Retrospectivos , Riboflavina/genética , Riboflavina/uso terapêutico
7.
Neuropsychiatr Dis Treat ; 16: 2817-2825, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33262596

RESUMO

PURPOSE: Nitrous oxide (N2O) abuse has become an increasingly severe problem in China. The aim of the study was to summarize the features of N2O-induced neurology and enhance the awareness of this disease among physicians. PATIENTS AND METHODS: We retrospectively reviewed the clinical, imaging, electrophysiological characteristics and the prognosis of patients with N2O neurotoxicity in our hospital from January 2016 to August 2019. RESULTS: Twenty-one patients (average age: 22.6±4.6 years) were collected. Eighty-six percent (18/21) patients presented with acute or subacute neurological disorders as their initial symptoms. The remaining fourteen percent (3/21) had psychiatric symptoms as the earliest symptoms. With progression, movement dysfunction appeared in ninety percent (19/21) of the patients with fifty-three percent (10/19) presented with weakness limited to both lower extremities. Sixty-two percent (13/21) of the patients presented with subjective sensory deficit. Seventy-one percent (15/21) had vibration sense impairment and positive Romberg's sign. Sixty-seven percent of the patients had hyporeflexia or areflexia. Fourteen percent (3/21) showed positive Babinski's sign. Seventy-eight percent (14/18) showed significantly increased homocysteine (HCY) level and only seventeen percent (3/18) showed decreased serum vitamin B12 level. T2 hyperintensity involving the posterior columns and lateral columns with inverted V sign in cervical spinal MRI had been observed in forty-seven percent (8/17) of the patients. Axonal peripheral neuropathy occurred in eighty-five percent (17/20) of the patients. The level of serum vitamin B12 and HCY, as well as imaging findings, were rapidly recovered after supplementation of Vitamin B12. CONCLUSION: The N2O-induced neuropsychiatric disturbances mainly occurred in the young groups and should be recognized by clinicians. The prognosis of N2O intoxication is relatively good.

8.
Environ Pollut ; 264: 114809, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32559883

RESUMO

The non-magnetic capping materials are difficult to be recycled from the water bodies after their application, leading to the increase in the cost of the sediment remediation. To address this issue, a capping material, i.e., magnetic lanthanum/iron-modified bentonite (M-LaFeBT) was prepared by loading lanthanum onto a magnetic iron-modified bentonite (M-FeBT) and used to control the internal phosphorus (P) loading in this study. To determine the capping efficiency and mechanism of M-LaFeBT, the impact of M-LaFeBT and M-FeBT capping on the mobilization of P in sediments was investigated, and the stabilization of P bound by the M-LaFeBT and M-FeBT capping layers was evaluated. Results showed that M-LaFeBT possessed good magnetic property with a saturated magnetization of 14.9 emu/g, and exhibited good phosphate adsorption ability with a maximum monolayer sorption capacity (QMAX) of 14.3 mg P/g at pH 7. Moreover, M-LaFeBT capping tremendously reduced the concentration of soluble reactive P (SR-P) in the overlying water (OL-water), and the reduction efficiencies were 94.7%-97.4%. Furthermore, M-LaFeBT capping significantly decreased the concentration of SR-P in the pore water and DGT (diffusive gradient in thin films)-labile P in the profile of OL-water and sediment. Additionally, most of P bound by the M-LaFeBT capping layer (approximately 77%) was stable under natural pH and reducing conditions. The phosphate adsorption ability for M-LaFeBT was much higher than that for M-FeBT, and the QMAX value for the former was 4.86 times higher than that for the latter. M-LaFeBT capping gave rise to a higher reduction of DGT-labile concentration in the profile of OL-water and sediment than M-FeBT capping. The P adsorbed by the M-LaFeBT capping layer was more stable than that by the M-FeBT capping layer. Results of this study demonstrate that M-LaFeBT is promising for utilization as an active capping material to intercept sedimentary P release into OL-water.


Assuntos
Fósforo , Poluentes Químicos da Água/análise , Bentonita , Sedimentos Geológicos , Ferro , Lagos , Lantânio , Fenômenos Magnéticos
9.
Environ Sci Pollut Res Int ; 27(4): 3962-3978, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31820252

RESUMO

Calcite/zeolite mixture (CZ) can be used to construct a capping layer for the simultaneous management of phosphorus (P) and nitrogen (N) liberation from sediments into the overlying water (OVER-water). However, its control efficiency of sedimentary P release still needs to be improved. To address this issue, an iron-modified CZ (Fe-CZ) was synthesized, characterized, and employed as a capping material to simultaneously prevent P and N release from sediments into OVER-water. Batch and microcosm incubation experiments were performed to study the efficiency and mechanism for the control of P and N release from sediments by capping Fe-CZ. Results showed that sediment capping with Fe-CZ resulted in the significant reduction of soluble reactive P (SRP) and ammonium-N (NH3-N) in OVER-water, with reduction rates of 77.8-99.7% and 54.0-96.7%, respectively. Furthermore, the Fe-CZ capping layer decreased the SRP concentration in the pore water (PORE-water) at depth of 0-30 mm and reduced the concentration of PORE-water NH3-N at depth of 0-50 mm. Moreover, the Fe-CZ capping layer gave rise to the great decrement of the concentration of the labile P measured by DGT (diffusive gradient in thin films) technology (P-DGT) in the profile of OVER-water and sediment. Additionally, the Fe-CZ capping resulted in the reduction of redox-sensitive P (P-BD) in the 0-50 mm sediment and caused the transformation of P-BD to calcium-bound P (P-HCl) and residual P (P-RES) in the 0-10 mm sediment as well as to P-RES in the 10-20 mm sediment. Results of this work indicate that the Fe-CZ capping has a high potential for the simultaneous management of P and N release from sediments, and the decrease of the contents of sediment P-DGT, sediment P-BD, PORE-water SRP and PORE-water NH3-N as well as the conversion of mobile P to more stable P in the top sediment should have a significant role in the simultaneous interception of sedimentary P and N liberation into OVER-water by the Fe-CZ capping.


Assuntos
Nitrogênio/química , Fósforo/química , Poluentes Químicos da Água , Zeolitas , Carbonato de Cálcio/química , Sedimentos Geológicos , Ferro/química
10.
J Environ Manage ; 249: 109369, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31400585

RESUMO

The use of zeolite as a geo-engineering tool has a high potential to control nitrogen (N) release from sediments, but its efficiency for controlling sedimentary phosphorus (P) release still need to be further increased. To address this issue, this work synthesized an iron-modified zeolite (IM-Z) by coating iron onto the surface of natural zeolite (NAT-Z) and then the as-obtained IM-Z was utilized as a geo-engineering material to block the upward mobilization of N and P from sediments to the overlying water. The efficiencies of IM-Z covering and amendment to prevent the liberation of N and P from sediments were evaluated, and the controlling mechanism was explored. Capping and amendment with IM-Z not only resulted in the tremendous reduction of the levels of ammonium-N (NH4+-N) and reactive soluble P (RSP) in the overlying water, but also led to the decrease of the contents of NH4+-N and RSP in the pore water. More importantly, sediment capping and amendment with IM-Z resulted in the formation of a static layer in the upper sediment directly below the sediment-water interface, with very low concentration of RSP in the pore water. In addition, IM-Z capping and addition effectively immobilized the diffusive gradients in thin films (DGT)-labile P in the overlying water and sediment. Furthermore, the decrease of the DGT-labile Fe concentrations in the overlying water as well as the top sediment were also observed after IM-Z capping and addition. Nearly 70% of P bound by IM-Z is stable and difficult to be released back into the overlying water under common pH and anoxic conditions. The adsorption of pore water NH4+-N on IM-Z, the immobilization of pore water RSP and DGT-labile P by IM-Z and the uptake of DGT-labile Fe on IM-Z played a significant role in the simultaneous control of NH4+-N and RSP liberation. Compared to NAT-Z, the efficiency of IM-Z to block the liberation of sedimentary P was higher. Results of this study demonstrate that IM-Z is suitable for use in the simultaneous interception of the upward transportation of NH4+-N and RSP from sediments into the overlying water.


Assuntos
Poluentes Químicos da Água , Zeolitas , Sedimentos Geológicos , Ferro , Nitrogênio , Fósforo
11.
Environ Sci Pollut Res Int ; 26(4): 3501-3516, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30519911

RESUMO

Three different types of zirconium-modified bentonites (ZrMBs) including zirconium-modified original bentonite (ZrMOB), zirconium-modified magnesium-pretreated bentonite (ZrMMgB), and zirconium-modified calcium-pretreated bentonite (ZrMCaB) were synthesized and used as active covering materials to suppress the release of phosphorus (P) from sediments. To assess the covering efficiency of ZrMBs to inhibit P release from sediments, we examined the impact of ZrMB covering layer on P mobilization in sediments at different depths as well as the release of P through the interface between sediment and overlying water (SWI) by use of simulating P release control experiments and diffusive gradients in thin films (DGT) technology. The results showed that the amount of soluble reactive P (SRP) in the overlying water greatly decreased after covering with ZrMBs. Moreover, both pore water SRP and DGT-liable P (DGT-P) in the top sediments decreased after capping with ZrMBs. An obvious stratification of DGT-P was observed along the vertical direction after covering with ZrMBs, and static and active layers were found in the top sediment and in the lower sediment directly below the static layer, respectively. Furthermore, ZrMB covering led to the change of P species from easily released P to relatively or very stable P, making P in the top sediment more stable compared to that without ZrMB covering. Besides, an overwhelming majority of P immobilized by ZrMBs is hard to be re-released into the water column in a common environment. Overall, the above results demonstrate that sediment covering with ZrMBs could effectively prevent the transport of SRP from sediments into the overlying water through the SWI, and the control of P transport into the overlying water by ZrMB covering could be mostly due to the immobilization of pore water SRP, DGT-P, and mobile P in the top sediment by ZrMBs.


Assuntos
Bentonita/química , Sedimentos Geológicos/química , Fósforo/química , Poluentes do Solo/química , Poluentes Químicos da Água/química , Poluição Química da Água/prevenção & controle , Zircônio/química
12.
Ann Neurol ; 84(5): 659-673, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30232818

RESUMO

OBJECTIVE: Riboflavin-responsive multiple acyl-coenzyme A dehydrogenation deficiency (RR-MADD) is an inherited fatty acid metabolism disorder mainly caused by genetic defects in electron transfer flavoprotein-ubiquinone oxidoreductase (ETF:QO). The variant ETF:QO protein folding deficiency, which can be corrected by therapeutic dosage of riboflavin supplement, has been identified in HEK-293 cells and is believed to be the molecular mechanism of this disease. To verify this hypothesis in vivo, we generated Etfdh (h)A84T knockin (KI) mice. METHODS: Tissues from these mice as well as muscle biopsies and fibroblasts from 7 RR-MADD patients were used to examine the flavin adenine dinucleotide (FAD) concentration and ETF:QO protein amount. RESULTS: All of the homozygous KI mice (Etfdh (h)A84T/(h)A84T , KI/KI) were initially normal. After being given a high-fat and vitamin B2 -deficient (HF-B2 D) diet for 5 weeks, they developed weight loss, movement ability defects, lipid storage in muscle and liver, and elevated serum acyl-carnitine levels, which are clinically and biochemically similar to RR-MADD patients. Both ETF:QO protein and FAD concentrations were significantly decreased in tissues of HF-B2 D-KI/KI mice and in cultured fibroblasts from RR-MADD patients. After riboflavin treatment, ETF:QO protein increased in proportion to elevated FAD concentrations, but not related to mRNA levels. These results were further confirmed in cultured fibroblasts from RR-MADD patients. INTERPRETATION: For the first time, we successfully developed a RR-MADD mice model and confirmed that FAD homeostasis disturbances played a crucial role on the pathomechanism of RR-MADD in this mouse model and culture cells from patients. Supplementation of riboflavin may stabilize variant ETF:QO protein by rebuilding FAD homeostasis. Ann Neurol 2018;84:667-681.


Assuntos
Flavoproteínas Transferidoras de Elétrons/genética , Flavina-Adenina Dinucleotídeo/metabolismo , Proteínas Ferro-Enxofre/genética , Deficiência Múltipla de Acil Coenzima A Desidrogenase/genética , Deficiência Múltipla de Acil Coenzima A Desidrogenase/metabolismo , Deficiência Múltipla de Acil Coenzima A Desidrogenase/fisiopatologia , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Animais , Modelos Animais de Doenças , Feminino , Técnicas de Introdução de Genes , Homeostase/fisiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mutação
13.
Mol Med Rep ; 15(2): 929-935, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28035355

RESUMO

Scutellarin is a flavonoid isolated from a medicinal herb Scutellaria barbata D. Don and exerts therapeutic effects on cardiovascular diseases. However, it remains unclear whether Scutellarin exhibits anti­tumor actions on human colon cancer. The current study aimed to investigate whether Scutellarin produces antiproliferative and pro­apoptotic effects on HCT­116 human colon cancer cells and to elucidate the mechanisms involved. Human colon cancer cells were exposed to different concentrations of Scutellarin, and cellular growth and apoptosis were evaluated by MTT assay, terminal deoxynucleotidyl transferase­mediated dUTP nick end labeling (TUNEL) staining, western blot analysis and other assays. A cell viability assay demonstrated that Scutellarin treatment reduced the viability of HCT­116 cells in a dose­ and time­dependent manner. TUNEL staining demonstrated that Scutellarin also induced apoptotic changes in HCT­116 cells. The expression level of the anti­apoptotic protein, Bcl­2 apoptosis regulator (Bcl­2), was reduced by Scutellarin in HCT­116 cells, whereas the expression Bcl­2 associated X apoptosis regulator (Bax) and the activation of caspase­3 protein were increased by Scutellarin treatment. Further investigation revealed that Scutellarin significantly increased the phosphorylation of p53 protein in HCT­116 cells. Additionally, suppression of p53 using a specific inhibitor, pifithrin­α, abrogated the pro­apoptotic effects of Scutellarin in HCT­116 cells. Collectively, Scutellarin reduced the viability and induced apoptosis of human colon carcinoma cells, potentially by regulating p53 and Bcl­2/Bax expression. These data suggested that Scutellarin may be useful as a promising anti­tumor drug for treating colon cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apigenina/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Glucuronatos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo , Antineoplásicos Fitogênicos/química , Apigenina/química , Proliferação de Células/efeitos dos fármacos , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Glucuronatos/química , Células HCT116 , Humanos , Reto/efeitos dos fármacos , Reto/metabolismo , Reto/patologia , Scutellaria/química
14.
J Asian Nat Prod Res ; 19(5): 444-447, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27660003

RESUMO

Chemical investigation on the ethyl acetate extract of the roots of Hedysarum multijugum resulted in the isolation of two new prenylated isoflavonoids: 5, 7, 2'-trihydroxy-4'-methoxy-3'-(γ, γ-dimethylallyl) isoflavone (hedysarimisoflavone A, 1) and 5, 7, 2'-trihydroxy-4'-methoxy-6, 8-di-(γ, γ-dimethylallyl) isoflavone (hedysarimisoflavone B, 2). Their structures were elucidated on the basis of spectroscopic analyses, especially, 1H and 13C NMR spectra in conjunction with their 2D experiments, 1H-1H COSY, HMQC, HMBC, and NOESY.


Assuntos
Medicamentos de Ervas Chinesas/isolamento & purificação , Fabaceae/química , Isoflavonas/isolamento & purificação , Medicamentos de Ervas Chinesas/química , Isoflavonas/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Raízes de Plantas/química , Prenilação
16.
Neurol Sci ; 36(6): 853-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25827849

RESUMO

We report a case with late onset riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency (MADD) characterized by decreased acyl-carnitine profile in serum which is consistent with primary systemic carnitine deficiency (CDSP) while just the contrary to a typical MADD. This patient complained with muscle weakness, muscle pain and intermittent vomiting, and was diagnosed as polymyositis, received prednisone therapy before consulted with us. Muscle biopsy revealed mild lipid storage. The findings of serum acyl-carnitines were consistent with CDSP manifesting as decreased free and total carnitines in serum. But oral L-carnitine supplementation was not very effective to this patient and mutation analysis of the SLC22A5 gene for CDSP was normal. Later, another acyl-carnitine analysis revealed a typical MADD profile in serum, which was characterized by increased multiple acyl-carnitines. Compound heterozygous mutations were identified in electron transferring-flavoprotein dehydrogenase (ETFDH) gene which confirmed the diagnosis of MADD. After administration of riboflavin, he improved dramatically, both clinically and biochemically. Thus, late onset riboflavin-responsive MADD should be included in the differential diagnosis for adult carnitine deficiency.


Assuntos
Acil Coenzima A/sangue , Carnitina/análogos & derivados , Flavoproteínas Transferidoras de Elétrons/genética , Proteínas Ferro-Enxofre/genética , Deficiência Múltipla de Acil Coenzima A Desidrogenase/genética , Mutação/genética , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Carnitina/uso terapêutico , Análise Mutacional de DNA/métodos , Humanos , Masculino , Deficiência Múltipla de Acil Coenzima A Desidrogenase/diagnóstico , Músculo Esquelético/patologia , Adulto Jovem
17.
Free Radic Biol Med ; 84: 161-170, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25843656

RESUMO

Fibroblast growth factor 21 (FGF21) is a growth factor with pleiotropic effects on regulating lipid and glucose metabolism. Its expression is increased in skeletal muscle of mice and humans with mitochondrial disorders. However, the effects of FGF21 on skeletal muscle in response to mitochondrial respiratory chain deficiency are largely unknown. Here we demonstrate that the increased expression of FGF21 is a compensatory response to respiratory chain deficiency. The mRNA and protein levels of FGF21 were robustly raised in skeletal muscle from patients with mitochondrial myopathy or MELAS. The mammalian target of rapamycin (mTOR) phosphorylation levels and its downstream targets, Yin Yang 1 (YY1) and peroxisome proliferator-activated receptor γ, coactivator 1α (PGC-1α), were increased by FGF21 treatment in C2C12 myoblasts. Activation of the mTOR-YY1-PGC1α pathway by FGF21 in myoblasts regulated energy homeostasis as demonstrated by significant increases in intracellular ATP synthesis, oxygen consumption rate, activity of citrate synthase, glycolysis, mitochondrial DNA copy number, and induction of the expression of key energy metabolic genes. The effects of FGF21 on mitochondrial function required phosphoinositide 3-kinase (PI3K), which activates mTOR. Inhibition of PI3K, mTOR, YY1, and PGC-1α activities attenuated the stimulating effects of FGF21 on intracellular ATP levels and mitochondrial gene expression. Our findings revealed that mitochondrial respiratory chain deficiency elicited a compensatory response in skeletal muscle by increasing the FGF21 expression levels in muscle, which resulted in enhanced mitochondrial function through an mTOR-YY1-PGC1α-dependent pathway in skeletal muscle.


Assuntos
Metabolismo Energético , Fatores de Crescimento de Fibroblastos/metabolismo , Síndrome MELAS/metabolismo , Músculo Esquelético/metabolismo , Transdução de Sinais , Animais , Linhagem Celular , Humanos , Camundongos , Mitocôndrias Musculares/metabolismo , Oxirredução , Consumo de Oxigênio , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Serina-Treonina Quinases TOR/metabolismo , Fatores de Transcrição/metabolismo , Fator de Transcrição YY1/metabolismo
18.
J Tradit Chin Med ; 34(2): 206-13, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24783935

RESUMO

OBJECTIVE: To study the effects of the drying processing in terms operational parameters on the bioactive constituents of six Yuanzhi (Radix Palygalae) samples across China. METHODS: Six Yuanzhi (Radix Palygalae) samples were investigated using thermogravimetry analysis. The heating courses were set in two ways: the temperature-programmed process from room temperature to 150 degrees C, and the constant-temperature course at 50 degrees C, 70 degrees C and 90 degrees C. RESULTS: The peak temperature of six Yuanzhi (Radix Palygalae) samples ranged from 78 degrees C to 88 degrees C. The mass loss rate of Yuanzhi (Radix Palygalae) alcohol-soluble extract was significantly increased when heated at 90 degrees C. Four types of bioactive ingredients were detected in volatile oils of Yuanzhi (Radix Palygalae) sample from Shanxi province by Gas Chromatography-mass spectrometry analysis. Fourier Transform Infrared Spectroscopy results showed that the drying temperature exerted a great influence on types and amount of ingredients of Yuanzhi (Radix Palygalae). The kinetic study showed that the constant-temperature drying process of Yuanzhi Radix Palygalae) samples could be well described by the Page Model, especially for the drying process at 50 degrees C, in which R2 and SD values were more than 0.98 and less than 0.04, respectively. The drying constant k of three Yuanzhi (Radix Palygalae) samples from Shanxi, Gansu and Shaanxi provinces in China was corresponding to the Arrhenius equation, and their activation energies were 28.07, 25.38 and 21.48 kJ/mol, respectively. CONCLUSION: The drying process of Yuanzhi (Radix Palygalae) was very important for bioactive ingredients improvement in Yuanzhi (Radix Palygalae). Temperature was a thermodynamic property significantly affecting the process.


Assuntos
Dessecação/métodos , Medicamentos de Ervas Chinesas/química , Magnoliopsida/química , Cromatografia Gasosa-Espectrometria de Massas , Temperatura Alta , Cinética
19.
Zhongguo Zhong Yao Za Zhi ; 38(12): 1951-60, 2013 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-24066591

RESUMO

OBJECTIVE: To compare the discrepancies between chemical constituents in Dao-di herb and non Dao-di herb of Huangqin (the root of Scutellaria baicalensis), study the impact of habitat and growth pattern (including cultivated and wild Huangqin) on chemical substances of Huangqin, and then provide evidence for the identification of Dao-di herb and quality evaluation of Huangqin. METHOD: The chemical constituents in Huangqin collected from different habitats and under different growth patterns, were analyzed using HPLC fingerprint. The fingerprints obtained were then evaluated by hierarchical clustering analysis, principal component analysis and components peak area pattern. RESULT: The fingerprints' chemical profiles of Dao-di herb and non Dao-di Huangqin had significant disparity. The fingerprints of modem Dao-di herb Huangqin samples originated from Chengde (Hebei Province) were significantly different from those from other habitats, though the fingerprints of the non Dao-di Huangqin collected from Chifeng (Inner Mongolia) and Chengde had high similarity to each other. The chemical characteristics of Huangqin samples collected from the habitats recorded in ancient herbals, such as Qingyang (Gansu Province), Yan'an (Shaanxi Province), Linyi (Shangdong Province), Changzhi and Jinzhong (Shanxi Province) were similar. The fingerprints of modern non Dao-di samples collected from Dingxi and Longnan (Gansu Province) and Shangluo (Shaanxi Province) had high similarity. In addition, the content of acteoside in wild Huangqin was higher than that in cultivated Huangqin. CONCLUSION: Dao-di herb and non Dao-di herb of Huangqin could be distinguished using the developed HPLC fingerprints. The results obtained may provide evidence for the quality control and pharmcodynamical research of Dao-di herb and non Dao-di Huangqin.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/normas , Scutellaria baicalensis/química , Medicamentos de Ervas Chinesas/análise , Controle de Qualidade
20.
Nat Prod Res ; 27(15): 1398-403, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23216207

RESUMO

In this study, a simple, sensitive and reliable fingerprint analysis method by high-performance liquid chromatography coupled with diode array detection was developed for raw materials of Hedysari Radix, which is a famous traditional Chinese medicine and widely used as a restorative food. Then the developed method was subsequently applied to analyse 48 samples collected or purchased from different origins. Twenty-six common fingerprint peaks, including six definitely identified peaks, were found in total, and were involved for further characterisation and quality evaluation of Hedysari Radix. The chemical quality of commercial samples and samples collected in spring varied obviously, while those of the cultivated samples collected in autumn were relatively stable, indicating that it is better to harvest Hedysari Radix in autumn and that more attention should be paid to the standardisation of the process of harvesting, manufacturing and storage of Hedysari Radix.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Fabaceae/química , Dermatoglifia , Medicamentos de Ervas Chinesas/química
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