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1.
Endocrine ; 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38446387

RESUMO

PURPOSE: To investigate the effect of nicotinamide (Nam) on diabetic kidney disease (DKD) in mice and explore its mechanism. METHODS: Thirty DBA/2 J mice were randomly assigned to three groups. After 8 weeks of hyperglycemia induced by streptozocin (STZ), Nam and saline were administrated to STZ + Nam and STZ + NS mice, respectively, for 8 weeks. Non-diabetic mice (NDM) were used as control group. Twenty In2-/- Akita mice were randomly divided into two groups. After 8 weeks of hyperglycemia, Nam and saline were administered to Akita + Nam and Akita + NS mice, respectively, for 6 weeks. Wild-type littermates were used as control group. Markers of renal injury were analyzed, and the molecular mechanisms were explored in human proximal tubular HK2 cells. RESULTS: Urinary albumin-to-creatinine ratio (UACR) and kidney injury molecule 1 (KIM-1) decreased in the STZ + Nam and Akita + Nam groups. Pathological analysis showed that Nam improved the structure of glomerular basement membrane, ameliorated glomerular sclerosis, and decreased the accumulation of extracellular matrix and collagen. Compared to the diabetic control group, renal fibrosis, inflammation, and oxidative stress were reduced in the Nam-treated mice. The expression of sirtuin 1 (Sirt1) in human proximal tubular HK2 cells was inhibited by high glucose and Nam treatment enhanced its expression. However, in HK2 cells with Sirt1 knockdown, the protective effect of Nam was abolished, indicating that the beneficial effect of Nam was partially dependent on Sirt1. CONCLUSIONS: Nam has a renoprotective effect against renal injury caused by hyperglycemia and may be a potential target for the treatment of DKD.

2.
Diabetes Res Clin Pract ; 206: 111014, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37977551

RESUMO

OBJECT: The highly conserved α-amino-ß-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) is the key enzyme that regulates the de novo NAD+ synthesis from tryptophan. NAD+ metabolism in diabetic cardiomyopathy (DCM) was not elucidated yet. METHODS: Mice were assigned to non-diabetic (NDM) group, streptozocin (STZ)-induced diabetic (DM) group, and nicotinamide (NAM) treated (DM + NAM) group. ACMSD mediated NAD+ metabolism were studied both in mice and patients with diabetes. RESULTS: NAD+ level was significantly lower in the heart of DM mice than that of the NDM group. Supplementation with NAM could partially increased myocardial capillary density and ameliorated myocardial fibrosis by increasing NAD+ level through salvage pathway. Compared with NDM mice, the expression of ACMSD in myocardial endothelial cells of DM mice was significantly increased. It was further confirmed that in endothelial cells, high glucose promoted the expression of ACMSD. Inhibition of ACMSD could increase de novo NAD+ synthesis and improve endothelial cell function by increasing Sirt1 activity. Targeted mass spectrometry analysis indicated increased ACMSD enzyme activity in diabetic patients, higher ACMSD activity increased risk of heart diastolic dysfunction. CONCLUSION: In summary, increased expression of ACMSD lead to impaired de novo NAD+ synthesis in diabetic heart. Inhibition of ACMSD could potentially improve DCM.


Assuntos
Carboxiliases , Cardiomiopatias Diabéticas , Animais , Humanos , Camundongos , Cardiomiopatias Diabéticas/tratamento farmacológico , Células Endoteliais/metabolismo , NAD/metabolismo , Carboxiliases/antagonistas & inibidores , Carboxiliases/metabolismo
3.
Front Endocrinol (Lausanne) ; 14: 1052227, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36755908

RESUMO

Objective: To investigate the association between anemia and progression of diabetic kidney disease (DKD) in type 2 diabetes. Methods: This was a retrospective study. A total of 2570 in-patients with type 2 diabetes hospitalized in Jinan branch of Huashan hospital from January 2013 to October 2017 were included, among whom 526 patients were hospitalized ≥ 2 times with a median follow-up period of 2.75 years. Annual rate of eGFR decline was calculated in patients with multiple admissions. A rate of eGFR decline exceeding -5 ml/min per 1.73 m2 per year was defined as rapid eGFR decline. The prevalence of DKD and clinical characteristics were compared between anemia and non-anemia patients. Correlation analysis was conducted between anemia and clinical parameters. Comparison of clinical features were carried out between rapid eGFR decline and slow eGFR decline groups. The risk factors for rapid DKD progression were analyzed using logistic regression analysis. Results: The prevalence of anemia was 28.2% among the 2570 diabetic patients, while in patients with DKD, the incidence of anemia was 37.8%. Patients with anemia had greater prevalence of DKD, higher levels of urinary albumin-to-creatinine ratio (UACR), serum creatinine, BUN, urine α1-MG, urine ß2-MG, urine NAG/Cr, hsCRP, Cystatin C, homocysteine and lower eGFR, as compared to the patients without anemia. Anemia was correlated with age, UACR, eGFR, urinary NAG/Cr, hsCRP and diabetic retinopathy (DR). Logistic regression analysis of 526 patients with type 2 diabetes during the follow-up period showed that anemia was an independent risk factor for rapid eGFR decline. Conclusion: Anemia is associated with worse renal function and is an independent risk factor for rapid eGFR decline in type 2 diabetes.


Assuntos
Anemia , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Estudos Retrospectivos , Proteína C-Reativa , Taxa de Filtração Glomerular , Albuminúria , Progressão da Doença , Fatores de Risco , Anemia/epidemiologia , Anemia/etiologia
4.
Food Sci Anim Resour ; 42(5): 800-815, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36133637

RESUMO

This study aimed to obtain high Fischer's ratio oligopeptides from goat whey (HFO) and investigate antioxidant property of it. Hydrolysis of goat whey was done with the approach of sequential digestion of pepsin and flavourzyme. With the adsorption of aromatic amino acids by activated carbon, HFO with a Fischer's ratio of 27.070 and a molecular weight of 200-1,000 Da were obtained, and the branched-chain amino acids accounted for 22.87%. Then the antioxidant activity of HFO was evaluated. At the concentrations of 2.0 mg/mL and 0.50 mg/mL, HFO scavenged 77.27% and 99.63% of 1,1-diphenyl-2-picrylhydrazyl and 3-ethylbenzthiazoline-6-sulphonate free radicals respectively. The scavenging rate of HFO against hydroxyl radicals reached 92.31% at the concentration of 0.25 mg/mL. Animal experiments demonstrated that HFO could moderate the changes of malondialdehyde, superoxide dismutase and glutathione peroxidase caused by CCl4-induced oxidative stress in vivo. This study indicated that HFO from goat whey was capable of oxidation resistance both in vivo and in vitro, which provided a scientific basis for the high-value processing and application of goat milk whey.

5.
Ultrason Sonochem ; 88: 106089, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35809472

RESUMO

This study investigated the effects of different treatment of alkaline pH-shifting on milk protein concentrate (MPC), micellar casein concentrate (MCC) and whey protein isolate (WPI) assisted by the same ultrasound conditions, including changes in the physicochemical properties, solubility and foaming capacity. The solubility of milk proteins had a significant increase with gradual enhancement of ultrasound-assisted alkaline pH-shifting (p < 0.05), especially for MCC up to 99.50 %. Also, treatment made a significant decline in the particle size of MPC and MCC, as well as the turbidity of the proteins (p < 0.05). The foaming capacity of MPC, MCC, and WPI was all improved, especially at pH 11, and at this pH, the milk protein also showed the highest surface hydrophobicity. The best foaming capacity at pH 11 was the result of the combined effect of particle size, potential, protein conformation, solubility, and surface hydrophobicity. In conclusion, ultrasound-assisted pH-shifting treatment was found to be effective in improving the physicochemical properties and solubility and foaming capacity of milk proteins, especially MCC, with promising application prospect in food industry.


Assuntos
Caseínas , Proteínas do Leite , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Micelas , Proteínas do Leite/química , Solubilidade , Proteínas do Soro do Leite/química
6.
Environ Microbiol ; 24(9): 4108-4123, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35416402

RESUMO

The consequences of soils exposed to hydraulic fracturing (HF) return fluid, often collectively termed flowback and produced water (FPW), are poorly understood, even though soils are a common receptor of FPW spills. Here, we investigate the impacts on soil microbiota exposed to FPW collected from the Montney Formation of western Canada. We measured soil respiration, microbial community structure and functional potentials under FPW exposure across a range of concentrations, exposure time and soil types (luvisol and chernozem). We find that soil type governs microbial community response upon FPW exposure. Within each soil, FPW exposure led to reduced biotic soil respiration, and shifted microbial community structure and functional potentials. We detect substantially higher species richness and more unique functional genes in FPW-exposed soils than in FPW-unexposed soils, with metagenome-assembled genomes (e.g. Marinobacter persicus) from luvisol soil exposed to concentrated FPW being most similar to genomes from HF/FPW sites. Our data demonstrate the complex impacts of microbial communities following FPW exposure and highlight the site-specific effects in evaluation of spills and agricultural reuse of FPW on the normal soil functions.


Assuntos
Fraturamento Hidráulico , Microbiota , Poluentes Químicos da Água , Microbiota/genética , Respiração , Solo , Microbiologia do Solo , Águas Residuárias/química , Água , Poluentes Químicos da Água/análise
7.
Horm Metab Res ; 54(1): 25-32, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34986497

RESUMO

The short-term effects of long-acting somatostatin analogues (SSAs) on lipid profiles in patients with acromegaly are not well studied. We retrospectively analyzed the effects of SSAs on lipid profiles and associated cardiovascular risk factors in a cohort of 120 newly diagnosed acromegaly patients. In this study, 69 females and 51 males were included. These patients were treated with either octreotide LAR (OCT) or lanreotide SR (LAN) for 3 months. After SSAs treatment, both GH and IGF-1 significantly decreased (p<0.001). Triglyceride (TG), total to high-density lipoprotein cholesterol (HDL-C) ratio, and lipoprotein (a) [Lp(a)] levels were significantly decreased, while HDL-C levels were increased (p<0.05). The reduction of mean serum GH (GHm) was positively associated with the decrease of TG (r=0.305, p=0.001) and Lp(a) (r=0.257, p=0.005), as well as the increase of HDL-C (r=-0.355, p<0.001). The changes of lipid profiles were observed only in OCT group, but not in LAN group. In addition, systolic blood pressure (SBP) had significantly declined after SSAs treatment, with an average reduction of 4.4 mmHg (126.7±1.28 vs. 122.3±1.44 mmHg, p=0.003), while no change was observed regarding diastolic blood pressure (DBP) (p>0.05). Fasting insulin, fasting C-peptide, and HOMA-IR were significantly decreased after SSAs treatment. In conclusion, our current study revealed that short-term SSAs treatment improves lipid profiles and other cardiovascular risk factors in patients with acromegaly.


Assuntos
Acromegalia/tratamento farmacológico , Acromegalia/metabolismo , Metabolismo dos Lipídeos , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Acromegalia/sangue , Acromegalia/diagnóstico , Adulto , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Feminino , Glucose/metabolismo , Hormônio do Crescimento Humano/sangue , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Lipídeos/sangue , Masculino , Estudos Retrospectivos , Carga Tumoral/efeitos dos fármacos
8.
Food Funct ; 12(22): 11343-11350, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34668899

RESUMO

Epigallocatechin gallate (EGCG) and ß-lactoglobulin (ßLg) were conjugated by covalent bonds to form EGCG-ßLg conjugates. This conjugation causes structural and bioactivity changes in ßLg, which in turn can be used as a possible approach for desensitization to allergens. In this study, the desensitization mechanism was investigated by monitoring ßLg secondary structure and immunoglobulin E (IgE) combining capacity changes on the basis of the conjugation mechanism. Furthermore, the desensitization efficiency in vivo was evaluated through animal experiments. The results show that temperature influenced the conjugation by decreasing the binding affinities (Ka) and binding numbers (n) of EGCG. The conjugation of EGCG decreased ßLg's IgE combining capacity by decreasing the ß-sheet component and imparted antioxidant properties by the introduction of hydroxyl groups. In addition, animal experiment results indicated that ßLg induced significant changes in the levels of IgE and inflammatory cytokines, and the relative abundance of small intestinal flora, linked to the inflammatory lesions and anaphylaxis symptoms. EGCG-ßLg conjugates can suppress the allergic response, attenuating serum IgE and relieving the anaphylaxis symptoms.


Assuntos
Catequina/análogos & derivados , Dessensibilização Imunológica , Lactoglobulinas , Alérgenos/imunologia , Animais , Catequina/química , Catequina/imunologia , Catequina/farmacologia , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/imunologia , Tolerância Imunológica/imunologia , Imunoglobulina E/imunologia , Lactoglobulinas/química , Lactoglobulinas/imunologia , Lactoglobulinas/farmacologia , Camundongos , Camundongos Endogâmicos BALB C
9.
iScience ; 24(9): 102983, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34485865

RESUMO

Rosiglitazone, a synthetic peroxisome proliferator-activated receptor γ (PPARγ) ligand, has been reported to reduce growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in 10 patients with acromegaly. However, the mechanisms remain unknown. Here, we reveal that PPARγ directly enhances 15-hydroxyprostaglandin dehydrogenase (15-PGDH) expression, whose expression is decreased and negatively correlates with tumor size in acromegaly. Rosiglitazone decreases GH production and promotes apoptosis and autophagy in GH3 and primary somatotroph adenoma cells and suppresses hepatic GH receptor (GHR) expression and IGF-1 secretion in HepG2 cells. Activating the PGE2/cAMP/PKA pathway directly increases GHR expression. Rosiglitazone suppresses tumor growth and decreases GH and IGF-1 levels in mice inoculated subcutaneously with GH3 cells. The above effects are all dependent on 15-PGDH expression. Rosiglitazone as monotherapy effectively decreases GH and IGF-1 levels in all nineteen patients with active acromegaly. Evidence suggests that rosiglitazone may be an alternative pharmacological approach for acromegaly by targeting both pituitary adenomas and liver.

10.
Environ Sci Pollut Res Int ; 28(48): 69393-69400, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34302245

RESUMO

Fluorapatite (FAp) is the largest phosphorous (P) reservoir on Earth. However, due to its low solubility, dissolved P is severely deficient in the pedosphere. Fungi play a significant role in P dissolution via excretion of organic acids, and in this regard, it is important to understand their impact on P cycling. The object of this study was to elucidate the balance between P release and F toxicity during FAp dissolution. The bioweathering of FAp was assisted by a typical phosphate-solubilizing fungus, Aspergillus niger. The release of elements and microbial activities were monitored during 5-day incubation. We found that the release of fluorine (F) was activated after day 1 (~90 mg/L), which significantly lowered the phosphate-solubilizing process by day 2. Despite P release from FAp being enhanced over the following 3 days, decreases in both the amount of biomass (52% decline) and the respiration rate (81% decline) suggest the strong inhibitory effect of F on the fungus. We thus concluded that F toxicity outweighs P supply, which in turn inhibits fungi growth and prevents further dissolution of FAp. This mechanism might reflect an underappreciated cause for P deficiency in soils.


Assuntos
Flúor , Fosfatos , Apatitas , Aspergillus niger , Fungos , Solubilidade
11.
Front Endocrinol (Lausanne) ; 12: 633904, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34017310

RESUMO

Objective: To determine the risk factors for erectile dysfunction (ED) in male patients with acromegaly and to prospectively investigate the short-term changes of erectile function after surgery or medical treatment. Methods: Sixty-three male patients were subjected to nocturnal penile tumescence and rigidity (NPTR) test for the evaluation of erectile function. The measurement of serum nitric oxide (NO) was also performed. Twenty-seven patients were re-evaluated by NPTR after surgery or long-term somatostatin analogues (SSA) treatment. Results: Twenty-two patients (34.9%) had ED. Patients with ED showed higher random GH (17.89 [10.97-44.19] µg/L vs 11.63 [4.31-28.80] µg/L, p = 0.020) and GH nadir (GHn) (10.80 [6.69-38.30] µg/L vs 8.76 [3.62-18.19] µg/L, p = 0.044) during oral glucose tolerance test (OGTT). The NO levels of ED patients were lower than non-ED patients (9.15 [5.58-22.48] µmol/L vs 16.50 [12.33-31.78] µmol/L, p = 0.012). After treatment, patients who present improvement in erectile function showed lower post-GHn (0.07 [0.03-0.12] ng/ml vs 1.32 [0.09-3.60] ng/ml, p = 0.048) and post-IGF-1 index (1.03 ± 0.38 vs 1.66 ± 0.95, p = 0.049). The multivariate analysis indicated post-GHn was still associated with the improvement of erectile function after correction of other covariates (OR: 0.059, 95% CI: 0.003-1.043, p = 0.053). Conclusions: Excessive GH is related to ED in male patients with acromegaly. GH normalization after treatment is beneficial for short-term erectile function recovery.


Assuntos
Acromegalia/complicações , Acromegalia/tratamento farmacológico , Acromegalia/cirurgia , Disfunção Erétil/complicações , Disfunção Erétil/diagnóstico , Hormônio do Crescimento Humano/metabolismo , Adenoma/metabolismo , Adulto , Endoscopia , Teste de Tolerância a Glucose , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Óxido Nítrico/sangue , Ereção Peniana , Estudos Prospectivos , Fatores de Risco , Somatostatina/análogos & derivados , Resultado do Tratamento
12.
Huan Jing Ke Xue ; 42(2): 952-959, 2021 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-33742891

RESUMO

Peppers are a high Cd-enriched vegetable. On the basis of a preliminary screening experiment of 91 pepper varieties and soil culture experiments during the entire growth period of 26 varieties, a high Cd variety (X15), medium Cd variety (X39), and two low varieties (X45 and X55) were selected to study the effect of different cadmium levels (0, 5, and 10 mg·kg-1 Cd) on enrichment, transport, and accumulation as well as its subcellular distribution and chemical form. Based on the results, 5 mg·kg-1 and 10 mg·kg-1 of Cd inhibited shoot dry weights of four pepper varieties but increased the root dry weights of X15, X45, and X55 varieties. Sodium chloride-bound cadmium and acetate-bound cadmium are the main forms of cadmium in the pepper fruits. Subcellular cadmium concentrations in the roots, leaves, and fruits of pepper plants were ranked in order cytoplasm > cell wall > organelle, and in the stems the order was cell wall > cytoplasm > organelle. Cd compartmentalization plays an important role in pepper resistance to cadmium stress. Under dosages of 5 mg·kg-1 Cd and 10 mg·kg-1 Cd, Cd concentrations in stems and leaves were ranked in order X39 > X15 > X55 > X45, with fruit Cd concentrations ranked in order X15 > X39 > X55 > X45. The Cd concentration was lowest in the roots of X15 whereas this variety has the highest concentrations in its fruit. The Cd concentrations in the roots, stems, and leaves of X39 were the highest among the four varieties whereas the concentration in the fruit was lower than in the X15 variety. The concentration of Cd in pepper fruits depends on the Cd transport capacity redistribution ability to the shoots.


Assuntos
Cádmio , Poluentes do Solo , Cádmio/análise , Cádmio/toxicidade , Frutas/química , Folhas de Planta/química , Raízes de Plantas/química , Poluentes do Solo/análise , Poluentes do Solo/toxicidade , Verduras
13.
RSC Adv ; 11(30): 18198-18204, 2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-35480918

RESUMO

Gold nanoparticles (AuNPs) provide a novel approach for protein enrichment and analysis due to their protein adsorption properties, forming a so called protein corona. This corona can significantly influence the protein's structure and characteristics, hindering their identification in situ. Dissociation is an important solution to analyze and identify the composition of protein coronas. However, a comprehensive picture of adsorbed protein dissociation is lacking. In this study, the protein dissociation from the protein corona and influencing factors were investigated on the basis of the formation mechanism and time evolution. Temperature and cysteine are the key factors influencing protein dissociation by altering the protein's binding ability. The results showed that half Au-S formation time is an important time point for thio-protein dissociation by the method of high speed centrifugation. When incubated for longer than that time, the thio-protein located in the hard corona could only be separated by ß-mercaptoethanol replacement under analytical ultracentrifugation. However, Fourier-transform infrared spectroscopy (FTIR) revealed significant changes that occurred in ßlg's secondary structure after ultracentrifugation. The Au-S bond formation time offers the potential to define the protein enrichment time of AuNPs.

14.
Chemistry ; 27(10): 3213-3228, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32633436

RESUMO

Owing to their non-toxic, stable, inexpensive properties, carboxylic acids are considered as environmentally benign alternatives as coupling partners in various organic transformations. Electrochemical mediated decarboxylation of carboxylic acid has emerged as a new and efficient methodology for the construction of carbon-carbon or carbon-heteroatom bonds. Compared with transition-metal catalysis and photoredox catalysis, electro-organic decarboxylative transformations are considered as a green and sustainable protocol due to the absence of chemical oxidants and strong bases. Further, it exhibits good tolerance with various functional groups. In this Minireview, we summarize the recent advances and discoveries on the electrochemical decarboxylative transformations on C-C and C-heteroatoms bond formations.

15.
J Biomed Mater Res B Appl Biomater ; 109(8): 1230-1238, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33354845

RESUMO

Dental caries is one of the most common disorders in dentistry. Typically, it is caused by the dissolution of the tooth mineral due to cariogenic organisms. Bioapatite is vulnerable to acid-etching ascribed to a variety of substitutions. This study applied Pb2+ cations to probe the dissolution of synthetic carbonated hydroxylapatite (CHAp) in the acidic environment induced by Enterobacter sp. It indicated a decreasing tendency of crystallite size (from ∼400 nm to 10-20 nm) during gradual incorporation of carbonate (from 2.5 to 13.8 wt %). Meanwhile, the shape of CHAp crystals was transformed from elongated to plate-like. Addition of Enterobacter sp. enhanced P release from CHAp (especially for the CHAp with ∼8 wt % CO3 ) around 10 times. Moreover, the bacterium provided a moderately acidic environment to cause more formation of stable pyromorphite over other Pb-minerals, for example, Pb3 (PO4 )2 , and PbCO3 . Then, transmission electron microscopy-energy dispersive X-Ray spectroscopy mapping successfully confirmed the Pb labeling on the newly formed phosphate mineral as Pb (with high-atomic weight) has strong signal under electron microscopy. This study therefore elucidated that Pb labeling has a bright future to explore the degradation of tooth mineral by microorganisms, as well as to evaluate the resistance of calcium phosphate dental restorative materials.


Assuntos
Cárie Dentária/microbiologia , Durapatita/metabolismo , Enterobacter/crescimento & desenvolvimento , Chumbo , Durapatita/química , Humanos , Chumbo/química , Chumbo/farmacologia
16.
Org Biomol Chem ; 18(31): 5994-6005, 2020 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-32692327

RESUMO

The nucleophilic substitution reactions of hydroxyl groups are one of the most fundamental and widely spread transformations in organic chemistry. Among them, PIII-mediated deoxygenative nucleophilic substitution reactions, such as the Mitsunobu reaction, are frequently used strategies and often require stoichiometric oxidants to activate PIII reagents to induce the desired reactions. It has been illustrated that PIII reagents can be oxidized into the corresponding radical cations through single-electron oxidation by photocatalysis or electro-oxidation. These phosphine radical cations can react with alcohols or carboxylic acids to form the corresponding alkoxyphosphonium or acyloxyphosphonium intermediates, which are very reactive and easily get decomposed. The release of tri-substituted phosphine oxides as a driving force triggers the following nucleophilic substitution. This strategy does not require the use of stoichiometric oxidants and it eludes safety and stability problems. In this review, we summarise the recent advances and discoveries in PIII-assisted direct deoxygenative reactions under photochemical or electrochemical conditions.

17.
J Clin Endocrinol Metab ; 105(3)2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31930294

RESUMO

CONTEXT: Metabolic disorders, especially dysregulated lipid metabolism, increase the risk of cardiovascular mortality in acromegaly. Previous studies measuring plasma macromolecular lipids have yielded conflicting results. PURPOSE: To explore the plasma lipid metabolite profiles by metabolomics analysis and identify potential metabolites associated with cardiac function in acromegaly. METHODS: Plasma was obtained from 80 newly diagnosed, untreated patients with acromegaly and 80 healthy controls. Echocardiography was performed. Based on the results of an oral glucose tolerance test (OGTT), patients were categorized into 2 groups: normal glucose tolerance (NGT, n = 28) and impaired glucose tolerance or diabetes mellitus (IGT/DM, n = 52). High-performance liquid chromatography-mass spectrometry (HPLC-MS)-based metabolomics analysis was conducted. Data were processed by principal components analysis (PCA), orthogonal partial least square-discriminant analysis (OPLS-DA), and MetaboAnalyst 4.0. Associations between metabolic substances and cardiovascular parameters were also explored. RESULTS: Metabolomics uncovered a distinct metabolic pattern between acromegaly and healthy controls, and perturbed pathways mainly include glycerophospholipid metabolism, sphingolipid metabolism, as well as linoleic acid metabolism. Collective analysis showed that phosphatidylethanolamine (PE) (22:6/16:0) was positively correlated with LV mass, while lysophosphatidylcholine (LysoPC) (16:0) was positively correlated with fractional shortening (FS) and left ventricle ejection fraction (LVEF). CONCLUSION: Patients with acromegaly have distinct lipid metabolite profiling, while PE (22:6/16:0) and LysoPC (16:0) are correlated with cardiac structure and function, which may contribute to the risk of cardiovascular complications.


Assuntos
Acromegalia/sangue , Lipídeos/sangue , Espectrometria de Massas/métodos , Metaboloma , Acromegalia/complicações , Acromegalia/diagnóstico por imagem , Acromegalia/metabolismo , Adulto , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão , Complicações do Diabetes/sangue , Complicações do Diabetes/diagnóstico por imagem , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico por imagem , Ecocardiografia , Feminino , Intolerância à Glucose/sangue , Intolerância à Glucose/complicações , Intolerância à Glucose/diagnóstico por imagem , Teste de Tolerância a Glucose , Humanos , Metabolismo dos Lipídeos , Transtornos do Metabolismo dos Lipídeos/sangue , Transtornos do Metabolismo dos Lipídeos/complicações , Transtornos do Metabolismo dos Lipídeos/diagnóstico por imagem , Lipídeos/análise , Masculino , Metabolômica/métodos , Pessoa de Meia-Idade
18.
Chem Commun (Camb) ; 55(100): 15089-15092, 2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-31782432

RESUMO

A dehydroxylative Csp3-N coupling reaction assisted by triphenylphosphine has been developed through electrochemical oxidation. The reaction proceeds via anodic oxidation of triphenylphosphine to generate its corresponding radical cation, followed by reacting with hydroxyl groups to form alkoxy triphenylphosphonium ions, which are trapped by azoles or amides to construct C-N bonds. This method provides an efficient electrochemical strategy of activating hydroxyl groups to form C-N bonds under mild conditions.

19.
Org Lett ; 21(22): 9262-9267, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31661284

RESUMO

Decarboxylative Csp3-N coupling reactions have been developed through electrochemical oxidation of amino acids. The reaction proceeds via anodic oxidative decarboxylation of carboxylic acids to form stabilized carbocations, which are trapped by azoles or amides to construct C-N bonds. This method avoids the preactivation of carboxylic acids and the use of expensive transition-metals and external chemical oxidants.

20.
Nutrition ; 67-68: 110565, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31561205

RESUMO

OBJECTIVES: Previous studies have shown that Roux-en-Y gastric bypass (RYGB) leads to rapid regression of obesity and type 2 diabetes (T2D). However, the underlying mechanism remains unclear. This study aimed to investigate the effect of RYGB on serum lipopolysaccharide (LPS), interleukin (IL)-1, IL-6, tumor necrosis factor alpha (TNF-α), and cecal microbiota in obese rats with T2D. METHODS: Obese Sprague-Dawley rats with T2D were randomly divided into RYGB diabetes operation (DO; n = 8), diabetes sham operation (DS; n = 8), and diabetic control (DC; n = 8) groups. Healthy Sprague-Dawley rats were grouped as normal control (NC; n = 8). Fasting plasma glucose and body weight were measured. The levels of peripheral serum LPS, IL-1, IL-6, and TNF-α were measured by enzyme-linked immunosorbent assay. The rats were sacrificed 12 wk after operation. Subsequently, a superior mesenteric venous blood sample was taken to measure serum LPS levels by enzyme-linked immunosorbent assay. The cecal contents of the DO and DS groups were taken to extract metagenomic DNA per the genomic DNA standardization procedure. The V4 region of the 16 S rRNA was sequenced with the Illumina Hiseq sequencing platform to compare the structure and relative abundance of cecal microbiota between the DO and DS groups. RESULTS: Twelve weeks after operation in the DO group, fasting plasma glucose and body weight showed a significant decrease (P < 0.05). Moreover, the levels of peripheral serum LPS, IL-1, IL-6, and TNF-α were obviously decreased (P < 0.05). A change in the LPS level of superior mesenteric venous blood also revealed a dramatic decrease (P < 0.05). Additionally, RYGB resulted in a shift of cecal microbiota in obese rats with T2D. CONCLUSIONS: Hypoglycemic effects after RYGB may be associated with improved levels of LPS, IL-1, IL-6, and TNF-α. Changes in the structure of cecal microbiota may also play an important role.


Assuntos
Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Tipo 2/sangue , Microbioma Gastrointestinal , Mediadores da Inflamação/sangue , Lipopolissacarídeos/sangue , Animais , Ceco/microbiologia , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Experimental/microbiologia , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/microbiologia , Modelos Animais de Doenças , Derivação Gástrica/efeitos adversos , Hipoglicemiantes/sangue , Obesidade/cirurgia , Período Pós-Operatório , Ratos , Ratos Sprague-Dawley
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