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1.
Arch Biochem Biophys ; 754: 109962, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38499055

RESUMO

Acetohydroxyacid synthase (AHAS) is one of the key enzymes of the biosynthesis of branched-chain amino acids, it is also an effective target for the screening of herbicides and antibiotics. In this study we present a method for preparing Escherichia coli AHAS I holoenzyme (EcAHAS I) with exceptional stability, which provides a solid ground for us to re-investigate the in vitro catalytic properties of the protein. The results show EcAHAS I synthesized in this way exhibits similar function to Bacillus subtilis acetolactate synthase in its catalysis with pyruvate and 2-ketobutyrate (2-KB) as dual-substrate, producing four 2-hydroxy-3-ketoacids including (S)-2-acetolactate, (S)-2-aceto-2-hydroxybutyrate, (S)-2-propionyllactate, and (S)-2-propionyl-2-hydroxybutyrate. Quantification of the reaction indicates that the two substrates almost totally consume, and compound (S)-2-aceto-2- hydroxybutyrate forms in the highest yield among the four major products. Moreover, the protein also condenses two molecules of 2-KB to furnish (S)-2-propionyl-2-hydroxybutyrate. Further exploration manifests that EcAHAS I ligates pyruvate/2-KB and nitrosobenzene to generate two arylhydroxamic acids N-hydroxy-N-phenylacetamide and N-hydroxy-N-phenyl- propionamide. These findings enhance our comprehension of the catalytic characteristics of EcAHAS I. Furthermore, the application of this enzyme as a catalyst in construction of C-N bonds displays promising potential.


Assuntos
Acetolactato Sintase , Escherichia coli , Acetolactato Sintase/química , Glicogênio Sintase , Hidroxibutiratos , Piruvatos , Holoenzimas
2.
Exp Physiol ; 106(7): 1631-1642, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33914383

RESUMO

NEW FINDINGS: What is the central question of this study? Diabetic nephropathy (DN) is a severe complication of diabetes correlated with a higher mortality rate in diabetic patients. Renal tubular injury participates in the pathogenesis of DN. We aimed to uncover the biological function of the NEAT1-miR-150-5p-DRP1 axis in an in vitro model of DN and elaborate the potential mechanisms. What is the main finding and its importance? NEAT1 facilitated high glucose-induced damage in HK-2 cells by reducing mitophagy via the miR-150-5p-DRP1 axis, which sheds light on DN pathogenesis and reveals a potential treatment for DN. ABSTRACT: Diabetic nephropathy (DN) is a severe complication in diabetic patients, with a high mortality rate. Renal tubular injury is involved in the pathogenesis of DN. In this study, we aimed to uncover the regulatory roles of the NEAT1-miR-150-5p-DRP1 axis in an in vitro model of DN and its possible mechanisms. High glucose-challenged HK-2 cells were used as an in vitro DN model. NEAT1, miR-150-5p and DRP1 levels were assessed by RT-qPCR. Cell viability was determined by the MTT assay. MitoSOX Red and JC-1 were used to evaluate intracellular production of reactive oxygen species and mitochondrial membrane potential, respectively. Lactate dehydrogenase release and superoxide dismutase activity were assessed with commercial kits. The protein levels of DRP1, p62, BECN1(beclin 1) and BNIP3 were determined by western blotting. The interaction between NEAT1 (DRP1) and miR-150-5p was verified by a dual-luciferase reporter assay and an RNA immunoprecipitation assay. Our results showed that in response to high glucose the NEAT1 and DRP1 levels were upregulated, whereas the miR-150-5p level was downregulated in HK-2 cells. Knockdown of NEAT1 or DRP1 in high glucose-challenged HK-2 cells inhibited excessive reactive oxygen species production and lactate dehydrogenase release, increased cell viability, mitochondrial membrane potential and superoxide dismutase activity and enhanced mitophagy. Inhibition of miR-150-5p resulted in the opposite results. Mechanistically, NEAT1 sponged miR-150-5p to increase the DRP1 level. Moreover, silencing of NEAT1 or DRP1 could counteract miR-150-5p inhibition-induced deleterious effects. Collectively, our findings indicate that NEAT1 facilitates high glucose-induced damage in HK-2 cells by suppressing mitophagy via the miR-150-5p-DRP 1 axis, which sheds light on a novel mechanism of DN.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , MicroRNAs , RNA Longo não Codificante , Diabetes Mellitus/metabolismo , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Dinaminas , Células Epiteliais/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Mitofagia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
3.
J Nat Prod ; 83(8): 2313-2319, 2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32683864

RESUMO

Six new structurally diverse indole alkaloids, melohemsines J-M (1-4), 11-hydroxy-Δ14-vincamine (5), and 11-hydroxy-16-epi-Δ14-vincamine (6), and 15 known alkaloids were isolated from the leaves and twigs of Melodinus hemsleyanus Diels. These new compounds and their absolute configurations were determined through spectroscopic data analyses, X-ray diffraction, and computational methods. Melohemsine J (1) is the first example of a melodinus-type alkaloid possessing a 6/6/5/5/6/5 hexacyclic skeleton and containing a tetrahydrofuro[2,3-b]pyridine-2(3H)-one unit. Melohemsine K (2) is an unusual aspidosperma-type alkaloid possessing a 6/5/6/5/5 pentacyclic architecture with a contracted E ring (loss of CH2). Compounds 5-10 and 16 exhibited vasorelaxant activities with EC50 values of 0.8-3.8 µM. In addition, compound 4 displayed moderate cytotoxicity toward the tumor cell lines HepG2 and A-549 with EC50 values of 18.7 and 28.7 µM, respectively.


Assuntos
Apocynaceae/química , Alcaloides Indólicos/química , Alcaloides Indólicos/farmacologia , Vasodilatação/efeitos dos fármacos , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Análise Espectral/métodos
4.
Stroke ; 50(10): 2708-2715, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31409266

RESUMO

Background and Purpose- Predicting the risk of stroke and determining intervention indications are highly important for patients with Moyamoya disease (MMD). Here, we evaluated a novel MMD grading system based on collateral circulation and Suzuki stage to evaluate symptoms and predict prognosis. Methods- In total, 301 idiopathic MMD patients were retrospectively analyzed between 2014 and 2016. A collateral circulation grading system with scores ranging from 1 to 12 was established: the anatomic extent of pial collateral blood flow from posterior cerebral artery to middle cerebral artery and anterior cerebral artery was scored from 1 to 6; perforator collateral and internal cerebral artery flow were scored as 6 to 1, which corresponded to Suzuki stages 1 to 6. Dynamic susceptibility contrast-magnetic resonance imaging was used to evaluate hemodynamic status. We assessed the association between the grading system and clinical characteristics. Results- We analyzed 364 symptomatic hemispheres of 301 patients (146 males, 28±16 years). Ischemic patients who presented with infarction were more likely to score <8 points (P<0.001), whereas those with ischemia symptoms (transient ischemic attack and headache) were more likely to score >8 points. Hemorrhagic patients who presented with intraparenchymal hemorrhage were more likely to score <8 points, whereas those who presented with intraventricular hemorrhage were more likely to score >8 points (P<0.001). According to dynamic susceptibility contrast-magnetic resonance imaging, lower scores were correlated with more severe time to peak delay (P<0.001) and worse relative cerebral blood volume ratio (P=0.016) and cerebral flow ratio (P=0.002). Encephaloduroarteriosynangiosis was performed in 348 symptomatic hemispheres. Patients who had collateral scores <4 points were more likely to have a postoperative stroke and a worse prognosis during the follow-up. Conclusions- This new MMD collateral grading system correlated well with clinical symptoms, hemodynamic status, and therapeutic prognosis and may facilitate risk stratification and prognosis predictions in patients with MMD.


Assuntos
Encéfalo/irrigação sanguínea , Circulação Cerebrovascular/fisiologia , Circulação Colateral/fisiologia , Doença de Moyamoya/patologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Adulto Jovem
5.
J Org Chem ; 84(22): 14892-14897, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31475536

RESUMO

Three new monoterpenoid indole alkaloids (MIAs), hunterines A-C (1-3), were isolated from Hunteria zeylanica. Compound 1 possesses a unique skeleton with an unprecedented azabicyclo[4.3.1]decane ring system. Compounds 2 and 3 are a pair of epimeric vobasinylindole alkaloid heterodimers. Their structures including absolute configurations were established by spectroscopic analyses, X-ray diffraction, computational calculation, and the modified Mosher's method. Plausible biogenetic pathways of 1-3 were also proposed. Alkaloid 1 showed moderate cytotoxic activity against the HepG2 cell line.

6.
J Org Chem ; 83(17): 10613-10618, 2018 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-30015492

RESUMO

Ervadivamines A (1) and B (2), two unprecedented trimeric monoterpenoid indole alkaloids, were isolated from Ervatamia divaricata. They are the first examples of vobasine-iboga-vobasine-type alkaloid with both C-C and C-N linkage patterns. Their structures including absolute configurations were fully accomplished by extensive spectroscopic analysis, single-crystal X-ray diffraction, and electric circular dichroism methods. The plausible biogenetic pathways of these trimeric alkaloids were also proposed. In addition, compound 1 exhibited significant cytotoxicity against four cancer cells.


Assuntos
Antineoplásicos/química , Polimerização , Alcaloides de Triptamina e Secologanina/química , Alcaloides de Triptamina e Secologanina/farmacologia , Tabernaemontana/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Humanos , Modelos Moleculares , Conformação Molecular
7.
Zhonghua Nan Ke Xue ; 24(6): 547-552, 2018 06.
Artigo em Zh | MEDLINE | ID: mdl-30173462

RESUMO

Objective: To study the effect of Erxian Decoction (EXD) on oligospermia (OS) induced by cyclophosphamide in mice. METHODS: Eighty 6-week-old male Kunming mice were randomly divided into five groups of equal number, normal control, OS model control, and low-, medium- and high-dose EXD, the former two groups treated intragastrically with normal saline and the latter three with EXD at 3, 6 and 12 g per kg of the body weight qd for 30 days. From the 21st day of administration, the mice of the normal control group were injected intraperitoneally with saline and those of the other four groups with cyclophosphamide at 80 mg per kg of the body weight qd for 5 consecutive days. At 24 hours after the last gavage, the bilateral epididymides of the mice were collected and sperm suspension prepared for determination of the sperm count and motility, and the bilateral testes were harvested for histomorphological observation and measurement of the concentrations of superoxide dismutase (SOD), malondialdehyde (MAD) and glutathione (GSH) in the testis tissue. RESULTS: Compared with the normal controls, the mice of the OS model control group showed significant decreases in epididymal sperm concentration (ï¼»9.31 ± 1.32ï¼½ vs ï¼»3.32 ± 1.13ï¼½×107/ml, P <0.01) and motility (ï¼»44.75 ± 8.12ï¼½% vs ï¼»25.95 ± 11.41], P<0.01) and the concentrations of SOD (ï¼»37.27 ± 0.99ï¼½ vs ï¼»14.23 ± 1.99ï¼½ U/mg prot, P <0.01) and GSH (ï¼»101.55 ± 8.74ï¼½ vs ï¼»58.77 ± 8.93ï¼½ µmol/L, P <0.01) but an obvious increase in the MDA level (ï¼»2.21 ± 0.65ï¼½ vs ï¼»2.61 ± 0.15ï¼½ nmol/mg prot, P <0.05) in the testis tissue. In comparison with the OS model controls, the mice treated with low-, medium- and high-dose EXD exhibited significantly increased epididymal sperm concentration (ï¼»8.34 ± 2.59ï¼½, ï¼»8.59 ± 1.10ï¼½ and ï¼»8.41 ± 1.47ï¼½×107/ml) (P <0.01) and motility (ï¼»36.04 ± 12.33ï¼½%, ï¼»38.87 ± 13.13ï¼½% and ï¼»41.90 ± 8.09ï¼½%) (P <0.01) and concentrations of SOD (ï¼»22.99 ± 1.11ï¼½, ï¼»20.82 ± 1.81ï¼½ and ï¼»21.33 ± 1.66ï¼½ U/mg prot) (P <0.01) and GSH (ï¼»104.74 ± 2.47ï¼½, ï¼»98.61 ± 12.98ï¼½ and ï¼»108.89 ± 5.85ï¼½ µmol/L) (P <0.01) but decreased level of MDA (P <0.05). CONCLUSIONS: Erxian Decoction can improve cyclophosphamide-induced reduction of sperm concentration and motility, which might be associated with its abilities of resisting oxidation and reducing oxidative stress injury.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Oligospermia/tratamento farmacológico , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Ciclofosfamida , Epididimo , Glutationa/análise , Masculino , Malondialdeído/análise , Camundongos , Oligospermia/induzido quimicamente , Estresse Oxidativo , Distribuição Aleatória , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Motilidade dos Espermatozoides/fisiologia , Superóxido Dismutase/análise , Testículo/anatomia & histologia , Testículo/química
8.
Zhongguo Zhong Yao Za Zhi ; 43(14): 2991-2998, 2018 Jul.
Artigo em Zh | MEDLINE | ID: mdl-30111060

RESUMO

To investigate the effect of Er-xian decoction on ovariectomy induced-learning and memory disability in rats based on the differences in hippocampus proteomic expression, the female rats were ovariectomized for perimenopausal status and then randomly divided into 3 groups, namely sham group, control group and Er-xian decoction group. The rats in sham group and control group were given normal saline by gavage everyday, the rats in Er-xian decoction group were given 12 g·kg⁻¹ of Er-xian decoction by gavage once a day. After treatment for 90 day, all of the animals were tested by Morris water maze, and all of the samples were collected for testing. The hippocampus proteins were detected by Nano-LC-LTQ-Orbitrap system, and identified by Protein Discovery software. The intensity of differential proteins were quantitated by SIEVE software,and the biological functions of protein were analyzed by DIVAD database. The results showed that Er-xian decoction could significantly improve the abilities of learning and memory. Compared with control group, 216 differential proteins with a consistent variation trend with the sham group were found in the Er-xian decoction group. And they mainly concentrated in calcium signaling pathway, Rab3A and Rab14 were key genes with the highest functional classification enrichment score in the gene group. Er-xian decoction could significantly improve the abilities of learning and memory in perimenopausal model rats. The invention effect of Er-xian decoction may be correlated with the calcium signaling pathway and Ras-related protein Rab-3A, and Ras-related protein Rab-14.


Assuntos
Hipocampo , Proteômica , Animais , Medicamentos de Ervas Chinesas , Feminino , Aprendizagem em Labirinto , Ovariectomia , Ratos , Ratos Sprague-Dawley
9.
J Asian Nat Prod Res ; 19(12): 1155-1159, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28347169

RESUMO

Three new areca alkaloids arecatemines A-C (1-3), together with five known ones (4-8), were isolated from the nuts of Areca catechu. The structures of new compounds including absolute configurations were elucidated using comprehensive spectroscopic and electronic circular dichroism (ECD). The known compounds were identified by comparing with data in the literature.


Assuntos
Alcaloides/isolamento & purificação , Areca/química , Nozes/química , Alcaloides/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular
10.
Zhongguo Zhong Yao Za Zhi ; 42(13): 2558-2563, 2017 Jul.
Artigo em Zh | MEDLINE | ID: mdl-28840699

RESUMO

This experiment was mainly aimed to investigate the effect of Er-xian decoction on osteoporosis and the femur proteomics in ovariectomized rats with osteoporosis. The female SD rats were randomly divided into sham operation group, model group, Alendronate group (1 mg•kg⁻¹), Er-xian decoction group (in dose of 8 g•kg⁻¹) according to their weight. The rats in sham operation group and model group were gavaged with normal saline; the rats in Alendronate group were gavaged with the Alendronate at the dose of 1 mg•kg⁻¹ and the rats in Er-xian decoction group were gavaged with Er-xian decoction at the dose of 8 g•kg⁻¹, once a day for continuous 90 days. Then the femoral bone mineral density (BMD) was detected. The femoral bone proteins were detected by NanoLC-LTQ-Orbitrap system, identified by Protein Discovery software, and the intensity of differentially expressed proteins were quantitated by SIEVE software. The results showed that Er-xian decoction could significantly improve femoral BMD in ovariectomized rats. As compared with model group, 41 differentially expressed proteins whose variation trend was consistent with the sham operation group, were found in Er-xian decoction group, mainly including biological oxidation related protein, signal transduction pathway related protein, proteins involved in aliphatic acid metabolism, cytoskeleton related protein, proteins involved in energy metabolism, and proteins involved in glucose metabolism etc. The osteoporosis could be prevented and cured by Er-xian decoction. The differentially expressed proteins such as carbonic anhydrase 2 and integrin ß1 may be the action targets for Er-xian decoction.


Assuntos
Densidade Óssea/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Osteoporose/tratamento farmacológico , Proteoma , Alendronato/farmacologia , Animais , Feminino , Fêmur/efeitos dos fármacos , Ovariectomia , Ratos , Ratos Sprague-Dawley
11.
Fitoterapia ; 175: 105928, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38548027

RESUMO

α-DCs (α-dicarbonyls) have been proven to be closely related to aging and the onset and development of many chronic diseases. The wide presence of this kind of components in various foods and beverages has been unambiguously determined, but their occurrence in various phytomedicines remains in obscurity. In this study, we established and evaluated an HPLC-UV method and used it to measure the contents of four α-DCs including 3-deoxyglucosone (3-DG), glyoxal (GO), methylglyoxal (MGO), and diacetyl (DA) in 35 Chinese herbs after they have been derivatized with 4-nitro-1,2-phenylenediamine. The results uncover that 3-DG is the major component among the α-DCs, being detectable in all the selected herbs in concentrations ranging from 22.80 µg/g in the seeds of Alpinia katsumadai to 7032.75 µg/g in the fruit of Siraitia grosuenorii. The contents of the other three compounds are much lower than those of 3-DG, with GO being up to 22.65 µg/g, MGO being up to 55.50 µg/g, and DA to 18.75 µg/g, respectively. The data show as well the contents of the total four α-DCs in the herbs are generally in a comparable level to those in various foods, implying that herb medicines may have potential risks on human heath in view of the α-DCs.


Assuntos
Desoxiglucose , Medicamentos de Ervas Chinesas , Glioxal , Aldeído Pirúvico , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/análise , Aldeído Pirúvico/análise , Cromatografia Líquida de Alta Pressão , Desoxiglucose/análogos & derivados , Desoxiglucose/análise , Glioxal/análise , Diacetil/análise , Estrutura Molecular , Frutas/química , Plantas Medicinais/química , Sementes/química
12.
Front Physiol ; 14: 1105891, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36998990

RESUMO

As one of the most common diseases in pediatric surgery, an inguinal hernia is usually diagnosed by medical experts based on clinical data collected from magnetic resonance imaging (MRI), computed tomography (CT), or B-ultrasound. The parameters of blood routine examination, such as white blood cell count and platelet count, are often used as diagnostic indicators of intestinal necrosis. Based on the medical numerical data on blood routine examination parameters and liver and kidney function parameters, this paper used machine learning algorithm to assist the diagnosis of intestinal necrosis in children with inguinal hernia before operation. In the work, we used clinical data consisting of 3,807 children with inguinal hernia symptoms and 170 children with intestinal necrosis and perforation caused by the disease. Three different models were constructed according to the blood routine examination and liver and kidney function. Some missing values were replaced by using the RIN-3M (median, mean, or mode region random interpolation) method according to the actual necessity, and the ensemble learning based on the voting principle was used to deal with the imbalanced datasets. The model trained after feature selection yielded satisfactory results with an accuracy of 86.43%, sensitivity of 84.34%, specificity of 96.89%, and AUC value of 0.91. Therefore, the proposed methods may be a potential idea for auxiliary diagnosis of inguinal hernia in children.

13.
Kaohsiung J Med Sci ; 39(11): 1106-1118, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37698291

RESUMO

Non-small cell lung cancer (NSCLC) accounts for ~85% of all lung cancer cases. Neferine is used as a traditional Chinese medicine with many pharmacological effects, including antitumor properties; however, it has not been reported whether neferine plays an anticancer role by causing pyroptosis in NSCLC cells. We used two typical lung cancer cell lines, A549 and H1299, and 42 lung cancer tissue samples to investigate the regulatory effects of neferine on TGF-ß and MST1. We also treated lung cancer cells with different concentrations of neferine to study its effects on lung cancer cell survival, migration, invasion, and epithelial-mesenchymal transition (EMT) as well as on pyroptosis. Lentivirus-mediated gain-of-function studies of TGF-ß and MST1 were applied to validate the roles of TGF-ß and MST1 in lung cancer. Next, we used murine transplanted tumor models to evaluate the effect of neferine treatment on the metastatic capacity of lung cancer tissues. With increasing neferine concentration, the viability, migration, invasion, and EMT capacity of A549 and H1299 cells decreased, whereas pyroptosis increased. Neferine repressed TGF-ß expression to modulate the induction of reactive oxygen species (ROS) by MST1. Overexpression of TGF-ß in either in vitro or mouse-transplanted A549 cells restored the inhibitory effect of neferine on tumor development. Overexpression of MST1 clearly enhanced pyroptosis. Neferine contributed to pyroptosis by regulating MST1 expression through downregulation of TGF-ß to induce ROS formation. Therefore, our study shows that neferine can serve as an adjuvant therapy for NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Animais , Camundongos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Piroptose , Linhagem Celular Tumoral , Movimento Celular , Transição Epitelial-Mesenquimal/genética
14.
Quant Imaging Med Surg ; 13(12): 7667-7679, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38106289

RESUMO

Background: Renal hemodynamic changes in early diabetes occur before the onset of significant structural abnormalities or clinical manifestations, and timely detection of these changes has clinical significance. This study aimed to evaluate renal elasticity and perfusion changes in an early-stage diabetic rat model by shear wave elastography (SWE) and contrast-enhanced ultrasound (CEUS), and to explore the potential correlations between renal elasticity and perfusion parameters. Methods: A total of 18 male Sprague-Dawley rats were randomly divided into three groups: a control group (group 1, n=6), a diabetic group (group 2, n=6), and a diabetic group receiving drug therapy (group 3, n=6). An intraperitoneal injection of streptozotocin (STZ) for 2 days combined with a high-fat diet (HFD) was used as the early-stage diabetic rat model. The diabetic rats in group 3 were treated with canagliflozin and losartan for 6 weeks, whereas the rats in groups 1 and 2 were given equal amounts of purified water. Renal stiffness on SWE and perfusion parameters on CEUS were measured and compared among the three groups, then the rats were sacrificed, and serum, urine, and renal histopathology were evaluated to confirm the development of early diabetes. Results: The early-stage diabetic rats without significant pathological changes exhibited bigger kidneys and higher blood glucose (all P<0.05). Among the CEUS parameters, peak enhancement (PE), wash-in area under the curve (WiAUC), wash-in perfusion index (WiPI), wash-out AUC (WoAUC), wash-in and wash-out AUC (WiWoAUC), rise time (RT), and time to peak (TTP) of diabetic rats in group 2 were significantly increased (all P<0.05), and the hyperperfusion ameliorated significantly after drug treatment. The renal elasticity measured by SWE varied in accordance with certain perfusion parameters, and was strongly positively correlated with WiAUC (r=0.701, P<0.001), WoAUC (r=0.647, P<0.001), and WiWoAUC (r=0.655, P<0.001), and moderately positively correlated with PE (r=0.539, P=0.001), WiPI (r=0.555, P<0.001), RT (r=0.425, P=0.010), and TTP (r=0.439, P=0.007). Conclusions: Renal elasticity and perfusion changes in the early stage of diabetes, and renal elasticity was positively associated with delayed and increased perfusion.

15.
Phytochemistry ; 211: 113678, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37059289

RESUMO

Eight unprecedented monoterpenoid indole alkaloid (MIA) adducts and dimers, melofusinines A-H (1-8), and three undescribed melodinus-type MIA monomers, melofusinines I-K (9-11), together with six putative biogenetic precursors were isolated from the twigs and leaves of Melodinus fusiformis Champ. ex Benth. Compounds 1 and 2 are unusual hybrid indole alkaloids incorporating an aspidospermatan-type MIA with a monoterpenoid alkaloid unit via C-C coupling. Compounds 3-8 feature the first MIA dimers constructed through an aspidospermatan-type monomer and a rearranged melodinus-type monomer with two different types of couplings. Their structures were elucidated by spectroscopic data, single crystal X-ray diffraction, and calculated electric circular dichroism spectra analysis. In addition, dimers 5 and 8 showed significant neuroprotection effects on MPP +-injured primary cortical neurons.


Assuntos
Antineoplásicos , Apocynaceae , Alcaloides de Triptamina e Secologanina , Monoterpenos/análise , Alcaloides Indólicos/farmacologia , Alcaloides Indólicos/análise , Folhas de Planta/química , Apocynaceae/química , Alcaloides de Triptamina e Secologanina/farmacologia , Alcaloides de Triptamina e Secologanina/química , Estrutura Molecular
16.
Biomed Pharmacother ; 166: 115339, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37595429

RESUMO

Postmenopausal women are prone to osteoporosis due to increased osteoclast activation and bone resorption caused by oestrogen deficiency. In Traditional Chinese Medicine theory, medicines with spleen- and kidney-nourishing effects are commonly used in postmenopausal osteoporosis (PMOP) treatment. Aikeqing (AKQ) is a compound Chinese medicinal granule with spleen- and kidney-nourishing effects. Herein, we investigate the in vitro and in vivo anti-osteoporotic effects of AKQ, its underlying mechanisms and pharmacodynamic basis. In vitro antiosteoporotic effects of AKQ were assessed by its ability to promote osteoblastogenesis in MC3T3-E1 and/or inhibit RANKL-induced osteoclastogenesis in murine bone marrow monocytes (BMMs). The protective effect of AKQ on bone loss induced by oestrogen deficiency was evaluated in ovariectomized rats. The underlying mechanisms were studied in BMMs by detecting the effects of AKQ on the RANKL-induced expression of genes and proteins involved in the regulation of osteoclastogenesis. The main chemical constituents of AKQ in the granule were analyzed by UPLC-QTOF-MS. Our findings show that AKQ did not affect osteoblastogenesis, but it inhibited RANKL-induced osteoclastogenesis. In the ovariectomized rats, oral administration of AKQ (4 g/kg/d) for 90 d effectively prevented oestrogen deficiency-induced bone loss. Mechanistic studies in BMMs revealed that AKQ inhibited RNAKL-induced activation of NF-κB (p65) and MAPKs (p38 and JNK) via blocking the RANK-TRAF6 interaction, subsequently suppressing the translocation and expression of NFATc1 and c-Fos. UPLC-QTOF-MS analysis quantified the 123 main components of AKQ. Taken together, AKQ was demonstrated for the first time as a novel alternative therapy for osteoclast-associated bone diseases.


Assuntos
Doenças Ósseas Metabólicas , Baço , Feminino , Ratos , Camundongos , Animais , Humanos , Osteogênese , Medicina Tradicional Chinesa , Rim , Estrogênios
17.
J Oral Pathol Med ; 41(10): 748-54, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22607258

RESUMO

BACKGROUND: The development of betel-quid (BQ) processing industry in Hunan has increased the usage of this substance and may produce significant health consequences. However, the update data for the prevalence of BQ chewing and its effect on oral submucous fibrosis (OSF) are limited. METHODS: A population-based survey was conducted to investigate the prevalence of BQ chewing and OSF in Hunan. A questionnaire interview and an oral examination were conducted. A multivariate logistic regression model was used to study the effect of socio-demographic characteristics on area-specific behaviors of BQ chewing. RESULTS: A total of 2356 subjects participated in this survey, with a 78.5% of response rate. The lifetime prevalence of BQ chewing was 16.2% (2.9% for ex-chewers and 13.3% for current-chewers). The findings from multivariate logistic regression model showed that a higher prevalence of this habit was among individuals who were males, urban residents, 15-49 years old, educated for 9-12 years, smokers, and drinkers. Male chewers occupied a fairly higher percentage of the combined use of tobacco and/or alcohol (86.1-87.5%) than the non-chewers (50.6-56.7%). The overall prevalence of OSF was 1.0%. Compared with the subjects without OSF (1.7-23.2%), a significantly higher proportion of OSF patients were a current-chewer (62.3% in men and 100.0% in women). CONCLUSIONS: BQ chewing is a vital risk factor for OSF in Hunan. A high prevalence of BQ chewing found among the younger cohort (15-49 years old) is an urgent warning for this oral premalignant disorder.


Assuntos
Areca , Fibrose Oral Submucosa/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , China/epidemiologia , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nozes , Fibrose Oral Submucosa/induzido quimicamente , Prevalência , Distribuição por Sexo , Adulto Jovem
18.
Sensors (Basel) ; 12(3): 3394-417, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22737015

RESUMO

Joint estimation of direction-of-arrival (DOA) and polarization with electromagnetic vector-sensors (EMVS) is considered in the framework of complex-valued non-orthogonal joint diagonalization (CNJD). Two new CNJD algorithms are presented, which propose to tackle the high dimensional optimization problem in CNJD via a sequence of simple sub-optimization problems, by using LU or LQ decompositions of the target matrices as well as the Jacobi-type scheme. Furthermore, based on the above CNJD algorithms we present a novel strategy to exploit the multi-dimensional structure present in the second-order statistics of EMVS outputs for simultaneous DOA and polarization estimation. Simulations are provided to compare the proposed strategy with existing tensorial or joint diagonalization based methods.

19.
Int J Cancer ; 129(7): 1741-51, 2011 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-21128235

RESUMO

Health risks stemming from betel-quid (BQ) chewing are frequently overlooked by people. Updated epidemiological data on the increased BQ use among Asian populations using comparable data collection methods have not been widely available. To investigate the prevalence, patterns of practice and associated types of oral preneoplastic disorders, an intercountry Asian Betel-quid Consortium study (the ABC study) was conducted for Taiwan, Mainland China, Malaysia, Indonesia, Nepal and Sri Lanka. A random sample of 8,922 subjects was recruited, and the data were analyzed using survey-data modules adjusted for the complex survey design. Chewing rates among men (10.7-43.6%) were significantly higher than women (1.8-34.9%) in Taiwan, Mainland China, Nepal and Sri Lanka, while women's rates (29.5-46.8%) were higher than that for men (9.8-12.0%) in Malaysia and Indonesia. An emerging, higher proportion of new-users were identified for Hunan in Mainland China (11.1-24.7%), where Hunan chewers have the unique practice of using the dried husk of areca fruit rather than the solid nut universally used by others. Men in the Eastern and South Asian study communities were deemed likely to combine chewing with smoking and drinking (5.6-13.6%). Indonesian women who chewed BQ exhibited the highest prevalence of oral lichen planus, oral submucous fibrosis and oral leukoplakia (9.1-17.3%). Lower schooling, alcohol drinking and tobacco smoking were identified as being associated with BQ chewing. In conclusion, the ABC study reveals the significant cultural and demographic differences contributing to practice patterns of BQ usage and the great health risks that such practices pose in the Asian region.


Assuntos
Areca/efeitos adversos , Neoplasias Bucais/epidemiologia , Lesões Pré-Cancerosas/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Povo Asiático , Cultura , Escolaridade , Ásia Oriental , Feminino , Humanos , Masculino , Mastigação , Pessoa de Meia-Idade , Prevalência , Fumar/epidemiologia
20.
Guang Pu Xue Yu Guang Pu Fen Xi ; 31(11): 2991-5, 2011 Nov.
Artigo em Zh | MEDLINE | ID: mdl-22242502

RESUMO

The non-local mean denoising (NLM) exploits the fact that similar neighborhoods can occur anywhere in the image and can contribute to denoising. However, these current NLM methods do not aim at multichannel remote sensing image. Smoothing every band image separately will seriously damage the spectral information of the multispectral image. Then the authors promote the NLM from two aspects. Firstly, for multispectral image denoising, a weight value should be related to all channels but not only one channel. So for the kth band image, the authors use sum of smoothing kernel in all bands instead of one band. Secondly, for the patch whose spectral feature is similar to the spectral feature of the central patch, its weight should be larger. Bringing the two changes into the traditional non-local mean, a new multispectral non-local mean denoising method is proposed. In the experiments, different satellite images containing both urban and rural parts are used. For better evaluating the performance of the different method, ERGAS and SAM as quality index are used. And some other methods are compared with the proposed method. The proposed method shows better performance not only in ERGAS but also in SAM. Especially the spectral feature is better reserved in proposed NLM denoising.

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