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1.
Pharmacol Res ; 200: 107054, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38181858

RESUMO

Diabetes, characterized as a well-known chronic metabolic syndrome, with its associated complications pose a substantial and escalating health and healthcare challenge on a global scale. Current strategies addressing diabetes are mainly symptomatic and there are fewer available curative pharmaceuticals for diabetic complications. Thus, there is an urgent need to identify novel pharmacological targets and agents. The impaired mitochondria have been associated with the etiology of diabetes and its complications, and the intervention of mitochondrial dysfunction represents an attractive breakthrough point for the treatments of diabetes and its complications. Natural products (NPs), with multicenter characteristics, multi-pharmacological activities and lower toxicity, have been caught attentions as the modulators of mitochondrial functions in the therapeutical filed of diabetes and its complications. This review mainly summarizes the recent progresses on the potential of 39 NPs and 2 plant-extracted mixtures to improve mitochondrial dysfunction against diabetes and its complications. It is expected that this work may be useful to accelerate the development of innovative drugs originated from NPs and improve upcoming therapeutics in diabetes and its complications.


Assuntos
Produtos Biológicos , Complicações do Diabetes , Diabetes Mellitus , Doenças Mitocondriais , Humanos , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Produtos Biológicos/metabolismo , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/metabolismo , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/metabolismo , Mitocôndrias/metabolismo , Doenças Mitocondriais/metabolismo , Estudos Multicêntricos como Assunto
2.
Inorg Chem ; 63(1): 462-473, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38141022

RESUMO

Adding hydrophilic ligands into aqueous solutions for the selective binding of actinides(III) is acknowledged as an advanced strategy in Ln(III)/An(III) separation. In view of the recycling and radioactive waste disposal of the minor actinide, there remains an urgent need to design and develop the appropriate ligand for selective separation of An(III) from Ln(III). Herein, four novel hydrophilic ligands with hard-soft hybrid donors, derived from the pyridine and phenanthroline skeletons, were designed and synthesized as masking agents for selective complexation of An(III) in the aqueous phase. The known N,N,N',N'-tetraoctyl diglycolamide (TODGA) was used as lipophilic extractant in the organic phase for extraction of Ln(III), and a new strategy for the competitive extraction of An(III) and Ln(III) was developed based on TODGA and the above hydrophilic ligands. The optimal hydrophilic ligand of N,N'-bis(2-hydroxyethyl)-2,9-dicarboxamide-1,10-phenanthroline (2OH-DAPhen) displayed exceptional selectivity toward Am(III) over Ln(III), with the concentrations of HNO3 ranging from 0.05 to 3.0 M. The maximum separation factors were up to 1365 for Eu/Am, 417.66 for Eu/Cm, and 42.38 for La/Am. The coordination mode and bonding property of 2OH-DAPhen with Ln(III) were investigated by 1H NMR titration, UV-vis spectrophotometric titration, luminescence titration, FT-IR, ESI-HRMS analysis, and DFT calculations. The results revealed that the predominant species formed in the aqueous phase was a 1:1 ligand/metal complex. DFT calculations also confirmed that the affinity of 2OH-DAPhen for Am(III) was better than that for Eu(III). The present work using a competitive extraction strategy developed a feasible alternative method for the selective separation of trivalent actinides from lanthanides.

3.
BMC Cardiovasc Disord ; 23(1): 22, 2023 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-36646995

RESUMO

BACKGROUND AND OBJECTIVE: The new non-invasive arterial stiffness indices, arterial pressure volume index (API) is explored as a novel marker of residual stress in the wall of the peripheral muscular arteries at zero-stress state in clinical settings. The present study aimed to study the association of API with cardiovascular disease (CVD) risk in China (China-PAR). METHODS: According to China-PAR score, participants were divided into three groups: low risk (< 5%), medium risk (5-9.9%), and high risk (≥ 10.0%). API ≥ 31 was defined as high API, and the incidences of high API were compared. Logistic regression models were used to analyze the risk factors of high API and high risk China-PAR categories. The association between China-PAR and API was analyzed by restrictive cubic spline. RESULTS: The study included 4311 participants. After adjustments for confounding factors, high API was independent factor associated with high risk China-PAR categories, and the probability of high API was 1.366 times higher than that in normal API subjects. While, the independent factors associated with high API were BMI, blood pressure and heart rate. Furthermore, API had a significant U-shaped association with China-PAR. CVD risk was lowest with API of 19 units, the fastest increase at 26 units and the flattest starting point at 59 units. CONCLUSION: API, an indicator of arterial stiffness and residual stress, had a U-shaped association with China-PAR score and might play an important role in predicting CVD risk in Chinese natural populations.


Assuntos
Doenças Cardiovasculares , Hipertensão , Rigidez Vascular , Humanos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Pressão Arterial , Fatores de Risco , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Pressão Sanguínea/fisiologia , Fatores de Risco de Doenças Cardíacas , China/epidemiologia , Rigidez Vascular/fisiologia , Análise de Onda de Pulso
4.
Neoplasma ; 67(6): 1293-1302, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32853022

RESUMO

Gastric cancer is one of the four major tumors in the world and the second leading cause of cancer-related death. It was reported that Substance P (SP), as an oncogenic factor, could regulate the expression of miRNAs in gastric cancer progression. Here, we focused on the role of miR-877-5p in gastric cancer development and the miR-877-5p involvement in the SP-mediated gastric cancer development. The mRNA expression level and cell proliferation were assessed by quantitative real-time PCR and cell counting kit-8 assay, respectively. Flow cytometry was conducted to detect apoptosis, followed by assessing the expression of related apoptosis factors. Dual-luciferase reporter assay was performed to validate the interaction between miR-877-5p and Forkhead cassette M1 (FOXM1). Our results showed that SP treatment significantly increased cell proliferation in gastric cancer. Moreover, the miR-877-5p expression was dose-dependently decreased by SP, whereas FOXM1 expression was markedly increased by SP in gastric cancer cells. miR-877-5p negatively regulated gastric cancer development via inhibiting cell proliferation and promoting apoptosis accompanied by increased cleaved caspase-3, cleaved caspase-9, and Bax protein levels and decreased Bcl-2 level. We confirmed that miR-877-5p could target FOXM1 and negatively regulate its expression. Furthermore, we demonstrated that SP could promote cell proliferation and inhibit apoptosis, while miR-877-5p overexpression reversed the effect of SP on cell proliferation and apoptosis. These results suggest that miR-877-5p overexpression can antagonize the promoting effect of SP on the development of gastric cancer, indicating that miR-877-5p may serve as a promising therapeutic target for gastric cancer.


Assuntos
MicroRNAs/genética , Neoplasias Gástricas , Substância P/genética , Linhagem Celular Tumoral , Proteína Forkhead Box M1/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Gástricas/genética
5.
Exp Physiol ; 103(1): 40-57, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-28971566

RESUMO

NEW FINDINGS: What is the central question of this study? The aim was to investigate the roles of extracellular chloride in electrical slow waves and resting membrane potential of mouse jejunal smooth muscle by replacing chloride with the impermeant anions gluconate and isethionate. What is the main finding and its importance? The main finding was that in smooth muscle cells, the resting Cl- conductance is low, whereas transmembrane Cl- movement in interstitial cells of Cajal (ICCs) is a major contributor to the shape of electrical slow waves. Furthermore, the data confirm that ICCs set the smooth muscle membrane potential and that altering Cl- homeostasis in ICCs can alter the smooth muscle membrane potential. Intracellular Cl- homeostasis is regulated by anion-permeable channels and transporters and contributes to excitability of many cell types, including smooth muscle and interstitial cells of Cajal (ICCs). Our aims were to investigate the effects on electrical activity in mouse jejunal muscle strips of replacing extracellular Cl- (Cl-o ) with the impermeant anions gluconate and isethionate. On reducing Cl-o , effects were observed on electrical slow waves, with small effects on smooth muscle membrane voltage (Em ). Restoration of Cl- hyperpolarized smooth muscle Em proportional to the change in Cl-o concentration. Replacement of 90% of Cl-o with gluconate reversibly abolished slow waves in five of nine preparations. Slow waves were maintained in isethionate. Gluconate and isethionate substitution had similar concentration-dependent effects on peak amplitude, frequency, width at half peak amplitude, rise time and decay time of residual slow waves. Gluconate reduced free ionized Ca2+ in Krebs solutions to 0.13 mm. In Krebs solutions containing normal Cl- and 0.13 mm free Ca2+ , slow wave frequency was lower, width at half peak amplitude was smaller, and decay time was faster. The transient hyperpolarization following restoration of Cl-o was not observed in W/Wv mice, which lack pacemaker ICCs in the small intestine. We conclude that in smooth muscle cells, the resting Cl- conductance is low, whereas transmembrane Cl- movement in ICCs plays a major role in generation or propagation of slow waves. Furthermore, these data support a role for ICCs in setting smooth muscle Em and that altering Cl- homeostasis in ICCs can alter smooth muscle Em .


Assuntos
Cloretos/fisiologia , Líquido Extracelular/fisiologia , Células Intersticiais de Cajal/fisiologia , Jejuno/fisiologia , Potenciais da Membrana/fisiologia , Músculo Liso/fisiologia , Animais , Cloretos/farmacologia , Líquido Extracelular/efeitos dos fármacos , Feminino , Células Intersticiais de Cajal/efeitos dos fármacos , Jejuno/citologia , Jejuno/efeitos dos fármacos , Masculino , Potenciais da Membrana/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Músculo Liso/efeitos dos fármacos , Técnicas de Cultura de Órgãos
6.
J Food Sci Technol ; 54(8): 2585-2593, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28740316

RESUMO

Mastication is the first step of food digestion, where foods are broken down and simultaneously impregnated by saliva resulting in the formation of semi-fluids known as food boluses. This review focuses on the impact of oral processing on texture attributes and taste perception. The article describes the oral actions in which texture characteristic are measured for the critical conditions that trigger swallowing. Taste perception also plays a key role in oral processing and oral sensations. There are still challenges in terms of determining different oral physiological characteristics. These include individual chewing behavior regardless of the temporal aspects of dominant processes of comminution, insalivation, bolus formation and swallowing. A comprehensive approach is essential to process favorable foods with respect to the food properties of texture and taste.

7.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(10): 3410-3, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30247001

RESUMO

In order to enhance the monitoring of paddy growth, utilize the fertilizer more efficiently, increase crop yield and improve the quality of grain, thus the system of laser-induced fluorescence (LIF) was built. The system was designed to study the relationship between the rice leaf chlorophyll content and fluorescence ratio. In this paper, the samples came from the second upper leaves of paddy in shooting stage and the cultivated area was located in Jianghan plain of China. Firstly, the Kjeldahl method combined with the formula which was described by Zivcak et al. was utilized to calculate the chlorophyll content of paddy, then the fluorescence spectrum of paddy leaf with different chlorophyll content by the instrument of laser-induced fluorescence (the wavelength of excitation 355 nm). Fluorescence spectra of paddy leaf with different chlorophyll content were collected and then a fluorescence spectra database was established. It is discussed that the relationship between the ratio of fluorescence (F740/F685 is the ratio of fluorescence intensity of 740 nm dividing that by 685 nm) and the chlorophyll content of paddy. It is found that the effect of chlorophyll content on the fluorescence spectral characteristics is evident. The results demonstrated that it has the tightly positive correlation between the fluorescence ratio (F740/F685) and chlorophyll content of paddy leaf. The determination coefficient (R2) can reach up to 0.901 3 and 0.912 5 at tillering stage and shooting stage, respectively. The experimental analysis showed that the LIF technology has the advantages of convenient, quick and nondestructive, and it has the potential for quantitative monitoring of crop growth.

8.
J Neurosci ; 33(31): 12638-46, 2013 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-23904600

RESUMO

Hydrogen sulfide (H2S) plays important roles in the enteric system in the wall of the gastrointestinal tract. There have been no studies on whether H2S is endogenously generated in peripheral sympathetic ganglia and, if so, its effect on synaptic transmission. In this study, we examined the effect of H2S on cholinergic excitatory fast synaptic transmission in the mouse superior mesenteric ganglion (SMG). Our study revealed that NaHS and endogenously generated H2S selectively potentiated cholinergic fast EPSPs (F-EPSPs) evoked by splanchnic nerve stimulation but not F-EPSPs evoked by colonic nerve stimulation. The H2S-producing enzyme cystathionine-γ-lyase (CSE) was expressed in both neurons and glial cells. The CSE blocker PAG (dl-propargylglycine) significantly reduced the amplitude of F-EPSPs evoked by splanchnic nerve stimulation but not F-EPSPs evoked by colonic nerve stimulation. Inhibiting the breakdown of endogenously generated H2S with stigmatellin potentiated the amplitude of F-EPSPs evoked by splanchnic nerve stimulation but not F-EPSPs evoked by colonic nerve stimulation. Splanchnic F-EPSPs but not colonic F-EPSPs were reduced in CSE knock-out (KO) mice. Functional studies showed that NaHS enhanced the inhibitory effect of splanchnic nerve stimulation on colonic motility. Colonic motility in CSE-KO mice was significantly higher than colonic motility in wild-type mice. We conclude that endogenously generated H2S acted selectively on presynaptic terminals of splanchnic nerves to modulate fast cholinergic synaptic input and that this effect of H2S modulates CNS control of gastrointestinal motility. Our results show for the first time that the facilitatory effect of endogenous H2S in the mouse SMG is pathway specific.


Assuntos
Acetilcolina/farmacologia , Fibras Autônomas Pré-Ganglionares/fisiologia , Agonistas Colinérgicos/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Gânglios Simpáticos/efeitos dos fármacos , Sulfeto de Hidrogênio/farmacologia , Animais , Colo Descendente/inervação , Cistationina gama-Liase/deficiência , Interações Medicamentosas , Estimulação Elétrica , Inibidores Enzimáticos/farmacologia , Potenciais Pós-Sinápticos Excitadores/genética , Antagonistas de Receptores de GABA-A/farmacologia , Gânglios Simpáticos/fisiologia , Motilidade Gastrointestinal/efeitos dos fármacos , Motilidade Gastrointestinal/genética , Cobaias , Sulfeto de Hidrogênio/metabolismo , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Nervos Esplâncnicos/fisiologia , Proteínas Vesiculares de Transporte de Acetilcolina/metabolismo
9.
Int J Biol Macromol ; 255: 128109, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37979742

RESUMO

Oat protein is becoming an important ingredient in beverages and formulated foods owing to its high nutritive value and bland flavor; yet, its functionality remains largely unexplored. This study sought to enhance the surface activity of oat protein isolate (OPI) through high-intensity ultrasound (HIU; at 20 or 60 °C) combined with high pressure homogenization (HP; 30 MPa) treatments. Sonication disturbed the protein conformation and significantly improved surface hydrophobicity (19.7%) and ζ-potential (15.7%), which were further augmented by subsequent HP (P < 0.05). Confocal microscopy revealed a uniform oil droplet distribution in emulsions prepared with HIU+HP combination treated OPI, and the oil droplet size decreased up to 35.6% when compared to that of non-treated OPI emulsion (d = 1718 nm). Emulsifying activity was greater for HIU+HP than for HIU, and the viscosity followed a similar trend. Moreover, while emulsions prepared with HIU or HP treated OPI were more stable than control, the 60 °C HIU+HP combination treatment yielded the maximum stability. In corroboration, a model salad dressing prepared from HIU+HP treated OPI displayed a homogenous oil droplet distribution and an improved viscosity. Therefore, thermosonication combined with high pressure homogenization may be suitable for salad dressings and other oil-imbedded food products.


Assuntos
Avena , Condimentos , Emulsões/química , Viscosidade , Interações Hidrofóbicas e Hidrofílicas
10.
Regen Ther ; 27: 365-380, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38694448

RESUMO

Brachial plexus injury (BPI) with motor neurons (MNs) damage still remain poor recovery in preclinical research and clinical therapy, while cell-based therapy approaches emerged as novel strategies. Previous work of rat skin precursor-derived Schwann cells (SKP-SCs) provided substantial foundation for repairing peripheral nerve injury (PNI). Given that, our present work focused on exploring the repair efficacy and possible mechanisms of SKP-SCs implantation on rat BPI combined with neurorrhaphy post-neurotomy. Results indicated the significant locomotive and sensory function recovery, with improved morphological remodeling of regenerated nerves and angiogenesis, as well as amelioration of target muscles atrophy and motor endplate degeneration. Besides, MNs could restore from oxygen-glucose-deprivation (OGD) injury upon SKP-SCs-sourced secretome treatment, implying the underlying paracrine mechanisms. Moreover, rat cytokine array assay detected 67 cytokines from SKP-SC-secretome, and bioinformatic analyses of screened 32 cytokines presented multiple functional clusters covering diverse cell types, including inflammatory cells, Schwann cells, vascular endothelial cells (VECs), neurons, and SKP-SCs themselves, relating distinct biological processes to nerve regeneration. Especially, a panel of hypoxia-responsive cytokines (HRCK), can participate into multicellular biological process regulation for permissive regeneration milieu, which underscored the benefits of SKP-SCs and sourced secretome, facilitating the chorus of nerve regenerative microenvironment. Furthermore, platelet-derived growth factor-AA (PDGF-AA) and vascular endothelial growth factor-A (VEGF-A) were outstanding cytokines involved with nerve regenerative microenvironment regulating, with significantly elevated mRNA expression level in hypoxia-responsive SKP-SCs. Altogether, through recapitulating the implanted SKP-SCs and derived secretome as niche sensor and paracrine transmitters respectively, HRCK would be further excavated as molecular underpinning of the neural recuperative mechanizations for efficient cell therapy; meanwhile, the analysis paradigm in this study validated and anticipated the actions and mechanisms of SKP-SCs on traumatic BPI repair, and was beneficial to identify promising bioactive molecule cocktail and signaling targets for cell-free therapy strategy on neural repair and regeneration.

11.
Wei Sheng Yan Jiu ; 42(2): 298-301, 2013 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-23654111

RESUMO

OBJECTIVE: To assess the validity and reliability of the infrared spectrometry for measuring the delta over baseline for breath 13C. METHOD: Twenty-four healthy adults were selected, including twelve males and twelve females. 13C-Leucine was used as tracer in stable isotope metabolic experiments. One baseline breath was collected before the tracer protocol began. Other breath samples were collected at 60, 120, 180, 195, 210, 225, 240, 255, 270 and 300 min post-tracer challenge. The delta over baseline for breath 13C was measured by the infrared spectrometry and Heliview 13C breath analyzer. RESULTS: No significant differences were found between the infrared spectrometry and Heliview 13C breath analyzer in measuring the delta over baseline for breath 13C. The F value and p value of two-way ANOVA were 0.29 and 0.5874 respectively. The t and p value of consistency test were 0.48 and 0.6346 respectively. CONCLUSION: The 13C infrared spectrometry can reliably measure the delta over baseline for breath 13C.


Assuntos
Testes Respiratórios/métodos , Isótopos de Carbono , Espectrofotometria Infravermelho/métodos , Adulto , Feminino , Humanos , Leucina , Masculino , Reprodutibilidade dos Testes
12.
Am J Hypertens ; 36(4): 201-208, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36645322

RESUMO

BACKGROUND: Hypertension is becoming a serious public health problem and noninvasive estimation of central hemodynamics and artery stiffness have been identified as important predictors of cardiovascular disease. METHODS: The study included 4,311 participants, both sex and aged between 20 and 79 years. Arterial velocity pulse index, arterial pressure-volume index (AVI, API, and the index of artery stiffness), central systolic blood pressure, central artery pulse pressure (CSBP, CAPP, and estimated via oscillometric blood pressure monitor), and 10-year risk score of cardiovascular disease in China (China-PAR) and Framingham cardiovascular risk score (FCVRS) were assessed at baseline. Regression model was performed to identify factors associated with high cardiovascular disease risk stratification. The relationships between CSBP, CAPP and China-PAR, and FCVRS were analyzed by restrictive cubic spline functions. RESULTS: The uncontrolled hypertension group showed the highest values of AVI, API, CSBP, and CAPP. In the regression analysis, CAPP and hypertension subtypes were identified as significant predictors of high cardiovascular risk stratification, and CAPP was strongly correlated with API in this cohort. Finally, CSBP and CAPP showed significant J-shaped relationships with China-PAR and FCVRS. CONCLUSIONS: Subjects with uncontrolled hypertension present with elevated values of CAPP, CSBP, API, AVI, China-PAR, and FCVRS scores. CAPP was independently associated with high cardiovascular risk stratification, and there was a significant J-shaped relationship with China-PAR and FCVRS that may identify people with higher cardiovascular risk.


Assuntos
Doenças Cardiovasculares , Hemodinâmica , Hipertensão , Rigidez Vascular , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Fatores de Risco de Doenças Cardíacas , Hipertensão/complicações , Hipertensão/diagnóstico , Análise de Onda de Pulso , Fatores de Risco , Rigidez Vascular/fisiologia
13.
Neurogastroenterol Motil ; 35(11): e14669, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37702100

RESUMO

BACKGROUND: Gastroparesis is defined by delayed gastric emptying (GE) without obstruction. Studies suggest targeting heme oxygenase-1 (HO1) may ameliorate diabetic gastroparesis. Upregulation of HO1 expression via interleukin-10 (IL-10) in the gastric muscularis propria is associated with reversal of delayed GE in diabetic NOD mice. IL-10 activates the M2 cytoprotective phenotype of macrophages and induces expression of HO1 protein. Here, we assess delivery of HO1 by recombinant adeno-associated viruses (AAVs) in diabetic mice with delayed GE. METHODS: C57BL6 diabetic delayed GE mice were injected with 1 × 1012 vg scAAV9-cre, scAAV9-GFP, or scAAV9-HO1 particles. Changes to GE were assessed weekly utilizing our [13 C]-octanoic acid breath test. Stomach tissue was collected to assess the effect of scAAV9 treatment on Kit, NOS1, and HO1 expression. KEY RESULTS: Delayed GE returned to normal within 2 weeks of treatment in 7/12 mice receiving scAAV9-cre and in 4/5 mice that received the scAAV9-GFP, whereas mice that received scAAV9-HO1 did not respond in the same manner and had GE that took significantly longer to return to normal (6/7 mice at 4-6 weeks). Kit, NOS1, and HO1 protein expression in scAAV9-GFP-treated mice with normal GE were not significantly different compared with diabetic mice with delayed GE. CONCLUSIONS AND INFERENCES: Injection of scAAV9 into diabetic C57BL6 mice produced a biological response that resulted in acceleration of GE independently of the cargo delivered by the AAV9 vector. Further research is needed to determine whether use of AAV mediated gene transduction in the gastric muscularis propria is beneficial and warranted.


Assuntos
Diabetes Mellitus Experimental , Gastroparesia , Camundongos , Animais , Dependovirus/genética , Interleucina-10 , Camundongos Endogâmicos NOD , Camundongos Endogâmicos C57BL
14.
Mol Pharm ; 9(8): 2127-35, 2012 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-22352697

RESUMO

The purposes of this study were to expand the structure of parent drugs selected for peptide transporter 1 (PepT1)-targeted ester prodrug design and to improve oral bioavailability of oleanolic acid (OA), a Biopharmaceutics Classification System (BCS) class IV drug. Through an ethoxy linker the carboxylic acid group of OA was conjugated with the carboxylic acid group of different amino acid promoieties to form six diester prodrugs. The effective permeability (P(eff)) of prodrugs was screened by in situ rat single-pass intestinal perfusion (SPIP) model in two buffers with different pH (6.0 and 7.4) as PepT1 employs a proton-gradient as the driving force. Compared to OA, 2.5-fold, 2.3-fold, 2.2-fold, 2.1-fold, and 1.9-fold enhancement of P(eff) in buffer with pH 6.0 was observed for L-Phe ester (5c), L-Val ester (5a), L-Lys ester (5e), D-Phe ester (5d), and D-Val ester (5b), respectively. Furthermore, P(eff) of 5a, 5c, 5d and 5e in pH 6.0 was significantly higher than that in pH 7.4 (p < 0.01), respectively. These results showed that the H(+) concentration of perfusion solution had great effect on the transport of the prodrugs across intestinal membrane. For the further evaluation of affinity to PepT1, inhibition studies were performed by coperfusing 0.1 mM prodrug with 50 mM glycyl-sarcosine (Gly-Sar, a typical substrate of PepT1). It turned out that the P(eff) of 5a, 5b, 5c and L-Tyr ester (6f) significantly reduced in the presence of Gly-Sar (1.7-fold, 2.2-fold, 1.9-fold, and 1.4-fold, respectively). We supposed that it may be attributed to PepT1 mediated transport of these prodrugs. 5a and 6f were selected as the optimal target prodrugs for oral absorption in vivo. Following intragastric administration of 300 mg/kg (calculated as OA) 5a, 6f and OA in three groups of rats, compared with group OA, Cmax for the group of 5a and 6f was enhanced by 1.56-fold and 1.54-fold, respectively. Fapp of group 5a and 6f was 2.21- and 2.04-fold increased, respectively, indicating that 5a and 6f had better oral absorption than OA. The combined results also suggest that diester prodrugs which conjugated two carboxylic acid groups of proper amino acid promoieties and parent drug through a linker can be used for PepT1-targeted prodrug design. With this strategy, oral bioavailability of OA in rats could be improved significantly.


Assuntos
Etilenoglicol/química , Ácido Oleanólico/química , Pró-Fármacos/química , Pró-Fármacos/farmacocinética , Animais , Absorção Intestinal , Masculino , Ratos , Ratos Sprague-Dawley , Solubilidade
15.
Food Res Int ; 156: 111179, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35651040

RESUMO

The structural properties, interfacial behavior, and emulsifying ability of ultrasound-treated pea protein isolate (PPI) and the legumin (11S) and vicilin (7S) globulin fractions prepared with a salt-solubilization procedure were investigated. Of the three protein groups, PPI was strongly responsive to ultrasound perturbation (20 kHz, 57-60 W·cm-2) showing the greatest solubility increase, particle size reduction, structure destabilization, and conformational change. Similar but less remarkable effects were observed on 11S globulins; 7S proteins, already highly soluble (>99%), were generally less sensitive to ultrasound. The ultrasound treatment significantly improved emulsifying activity, which resulted in greater emulsifying capacity and stronger interfacial adsorption for all protein samples. PPI exhibited the higher activity increase (70.8%) compared to approximately 30% for 11S and 7S. For both control and ultrasound treated proteins, the emulsifying capacity was in the order of 7S > 11S > PPI, inversely related to the trend of protein loading at the interface, indicating efficiency differences. The latter was attributed to emulsion clusters formed through protein-protein interaction in PPI and 11S emulsions which were visibly absent in 7S emulsions.


Assuntos
Fabaceae , Globulinas , Proteínas de Ervilha , Emulsões , Fabaceae/química , Globulinas/química , Pisum sativum/química , Proteínas de Armazenamento de Sementes/química , Verduras
16.
Polymers (Basel) ; 14(16)2022 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-36015634

RESUMO

With the fast consumption of traditional fossil fuels and the urgent requirement for a low-carbon economy and sustainable development, supercapacitors are gaining more and more attention as a clean energy storage and conversion device. The research on electrode materials for supercapacitors has become a hot topic nowadays. An electrode material for a supercapacitor, comprising the ZIF-67 in-built carbon-based material, was prepared from a biomass pre-hydrolysate via a hydrothermal process. As a by-product of dissolving slurry, the pre-hydrolysate is rich in carbon, which is an excellent biomass resource. The utilization of pre-hydrolysate to prepare carbon energy materials could realize the high value utilization of pre-hydrolysate and the efficient energy conversion of biomass. Meanwhile, the cobalt-based MOF (such as ZIF-67), as a porous crystalline material, has the advantages of having a regular order, high specific surface area and controllable pore size, as well as good thermal and chemical stability. The addition of ZIF-67 modified the morphology and pore structure of the carbon, and the obtained samples showed outstanding electrochemical performance. One- and two-step synthetic processes generated specimens with a coral-like cross-linked structure and a new type of rough, hollow, dandelion-like structure, respectively, and the pore size was in the range of 2.0-5.0 nm, which is conducive to ion transport and charge transfer. In C2-ZIF-67, the hollow structures could effectively prevent the accumulation of the electrochemical active center, which could provide enough space for the shrinkage and expansion of particles to protect them from the interference of electrolytes and the formation of solid electrolyte interphase film layers. Additionally, the plush tentacle structure with low density and a large specific surface area could expose more active sites and a large electrolyte electrode contact area, and short electron and charge transport paths. Importantly, active, free electrons of small amounts of Co-MOF (1 wt%) could be stored and released through the redox reaction, further improving the electrical conductivity of Carbon-ZIF-67 materials in this work. Consequently, C2-ZIF-67 exhibited superior specific capacitance (400 F g-1, at 0.5 A g-1) and stability (90%, after 10,000 cycles).

17.
Front Chem ; 10: 991230, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36051623

RESUMO

Here, a Co-Metal Organic Framework/pre-hydrolysis (Co-MOF/pre-hydrolysis) solution carbon material is prepared by a mild and environmentally-friendly hydrothermal carbonization technique using a pulping pre-hydrolysis solution as the raw material and Co-MOF as the metal dopant. The stable hollow structure provide sufficient space for particle shrinkage and expansion, while the low density and large specific surface area of the long, hairy tentacle structure provide a greater contact area for ions, which shorten the transmission path of electrons and charges. The materials exhibit excellent specific capacitance (400 F/g, 0.5 A/g) and stability (90%, 10,000 cycles). The Change of different concentration ratios in the structures significantly affect the electrochemical performance. The specific surface area of the carbon materials prepared by ultra-filtration increased, but the specific surface area decrease as ultrafiltration concentration increase. The specific capacitance decrease from 336 F/g for C-ZIF-67-1/3 volume ultrafiltration to 258 F/g for C-ZIF-67-1/5 ultrafiltration. The results indicate that energy storage by the carbon materials relied on a synergistic effect between their microporous and mesoporous structures. The micropores provide storage space for the transmission of ions, while the mesopores provide ion transport channels. The separation of large and small molecules after ultrafiltration concentration limit the ion transmission and energy storage of the pores.

18.
Clin Hemorheol Microcirc ; 82(3): 255-263, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35848014

RESUMO

AIM: Carotid ultrasound is a key tool for the diagnosis and evaluation of cardio disease, and the measurement of carotid intima-media thickness (CIMT) and hemodynamic parameters is of paramount importance for the imaging method. The aim of this study was to evaluate the feasibility and accuracy of handheld ultrasound devices for measuring carotid parameters. METHODS: We performed a carotid ultrasound on 25 participants using a handheld ultrasound device and a conventional ultrasound machine. For each participant, max and mean CIMT of common carotid artery (CCA) and peak systolic velocity (PSV), end diastolic velocity (EDV) and resistive index (RI) of CCA, bilateral external carotid artery (ECA), internal carotid artery (ICA) and the vertebral artery were measured. Agreement and repeatability were evaluated by linear regression and Bland-Altman analysis. RESULTS: We found a good repeatability and consistent of handheld ultrasound device in measuring mean CIMT (r = 0.68, P < 0.01). Furthermore, there was a moderate to good agreement between handheld and conventional ultrasound systems in measuring max IMT, mean IMT, PSV, EDV and RI of CCA (0.73, 0.79, 0.52, 0.58 and 0.84, respectively). CONCLUSION: Handheld ultrasound devices were able to provide carotid IMT and hemodynamic parameters measurements similar to those of conventional ultrasound. Such capabilities of handheld ultrasound devices might be useful for the primary assessment of carotid in clinical work.


Assuntos
Artéria Carótida Primitiva , Espessura Intima-Media Carotídea , Humanos , Artéria Carótida Primitiva/diagnóstico por imagem , Artéria Carótida Interna/diagnóstico por imagem , Artérias Carótidas/diagnóstico por imagem , Ultrassonografia , Velocidade do Fluxo Sanguíneo
19.
Front Public Health ; 10: 904569, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35712292

RESUMO

The COVID-19 pandemic gives humankind a lesson that the outbreak of an emerging infectious disease (EID) is sudden and uncertain. Accurately mastering its dynamics and putting forward an efficient and fair humanitarian logistics plan for personal protective equipment (PPE) remains difficult. This study examines the decision making for humanitarian logistics to answer the question that how to coordinate fairness and efficiency when facing supply-demand imbalance during humanitarian logistics planning in an EID environment. The main contributions include two aspects: (1) The victims' losses in terms of fairness and efficiency in receiving PPE are jointly explored by evaluating their bearing capacity evolution, and then a novel loss function is built to search for a reasonable compromise between fairness and efficiency. (2) A multi-objective optimization model is built, which is solved using the combined use of goal programming approach and improved branch and bound method. Finally, the practicability of the proposed model is tested by an EID case study. The potential advantages of the proposed model and improved approach are discussed.


Assuntos
COVID-19 , Doenças Transmissíveis Emergentes , COVID-19/prevenção & controle , Doenças Transmissíveis Emergentes/prevenção & controle , Pessoal de Saúde , Humanos , Pandemias , Equipamento de Proteção Individual
20.
Am J Physiol Gastrointest Liver Physiol ; 300(6): G1105-14, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21393430

RESUMO

Hydrogen sulfide (H(2)S) is produced endogenously by L-cysteine metabolism. H(2)S modulates several ion channels with an unclear mechanism of action. A possible mechanism is through reduction-oxidation reactions attributable to the redox potential of the sulfur moiety. The aims of this study were to determine the effects of the H(2)S donor NaHS on Na(V)1.5, a voltage-dependent sodium channel expressed in the gastrointestinal tract in human jejunum smooth muscle cells and interstitial cells of Cajal, and to elucidate whether H(2)S acts on Na(V)1.5 by redox reactions. Whole cell Na(+) currents were recorded in freshly dissociated human jejunum circular myocytes and Na(V)1.5-transfected human embryonic kidney-293 cells. RT-PCR amplified mRNA for H(2)S enzymes cystathionine ß-synthase and cystathionine γ-lyase from the human jejunum. NaHS increased native Na(+) peak currents and shifted the half-point (V(1/2)) of steady-state activation and inactivation by +21 ± 2 mV and +15 ± 3 mV, respectively. Similar effects were seen on the heterologously expressed Na(V)1.5 α subunit with EC(50)s in the 10(-4) to 10(-3) M range. The reducing agent dithiothreitol (DTT) mimicked in part the effects of NaHS by increasing peak current and positively shifting steady-state activation. DTT together with NaHS had an additive effect on steady-state activation but not on peak current, suggesting that the latter may be altered via reduction. Pretreatment with the Hg(2+)-conjugated oxidizer thimerosal or the alkylating agent N-ethylmaleimide inhibited or decreased NaHS induction of Na(V)1.5 peak current. These studies show that H(2)S activates the gastrointestinal Na(+) channel, and the mechanism of action of H(2)S is partially redox independent.


Assuntos
Sulfeto de Hidrogênio/metabolismo , Jejuno/metabolismo , Músculo Liso/metabolismo , Miócitos de Músculo Liso/metabolismo , Canais de Sódio/metabolismo , Sódio/metabolismo , Alquilantes/farmacologia , Cistationina beta-Sintase/metabolismo , Cistationina gama-Liase/metabolismo , Ditiotreitol/farmacologia , Relação Dose-Resposta a Droga , Etilmaleimida/farmacologia , Células HEK293 , Humanos , Jejuno/efeitos dos fármacos , Potenciais da Membrana , Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Canal de Sódio Disparado por Voltagem NAV1.5 , Oxidantes/farmacologia , Oxirredução , Técnicas de Patch-Clamp , Substâncias Redutoras/farmacologia , Canais de Sódio/efeitos dos fármacos , Canais de Sódio/genética , Sulfetos/farmacologia , Timerosal/farmacologia , Transfecção
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