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1.
Front Cell Infect Microbiol ; 11: 613149, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33796474

RESUMO

Tuberculosis (TB) remains a global health problem despite almost universal efforts to provide patients with highly effective chemotherapy, in part, because many infected individuals are not diagnosed and treated, others do not complete treatment, and a small proportion harbor Mycobacterium tuberculosis (Mtb) strains that have become resistant to drugs in the standard regimen. Development and approval of new drugs for TB have accelerated in the last 10 years, but more drugs are needed due to both Mtb's development of resistance and the desire to shorten therapy to 4 months or less. The drug development process needs predictive animal models that recapitulate the complex pathology and bacterial burden distribution of human disease. The human host response to pulmonary infection with Mtb is granulomatous inflammation usually resulting in contained lesions and limited bacterial replication. In those who develop progressive or active disease, regions of necrosis and cavitation can develop leading to lasting lung damage and possible death. This review describes the major vertebrate animal models used in evaluating compound activity against Mtb and the disease presentation that develops. Each of the models, including the zebrafish, various mice, guinea pigs, rabbits, and non-human primates provides data on number of Mtb bacteria and pathology resolution. The models where individual lesions can be dissected from the tissue or sampled can also provide data on lesion-specific bacterial loads and lesion-specific drug concentrations. With the inclusion of medical imaging, a compound's effect on resolution of pathology within individual lesions and animals can also be determined over time. Incorporation of measurement of drug exposure and drug distribution within animals and their tissues is important for choosing the best compounds to push toward the clinic and to the development of better regimens. We review the practical aspects of each model and the advantages and limitations of each in order to promote choosing a rational combination of them for a compound's development.

2.
Zhen Ci Yan Jiu ; 46(3): 187-93, 2021 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-33798290

RESUMO

OBJECTIVE: To investigate the effect of electroacupuncture (EA) at "Taichong"(LR3) on blood pressure, sympathetic nerve activity, baroreflex sensitivity, and α 2-adrenergic receptor (α2AR) expression in nucleus tractus solitarii (NTS) in hypertensive rats, so as to reveal its mechanisms underlying improvement of hypertension. METHODS: Male Sprague Dawley rats were randomly divided into 4 groups: sham-operation, model, EA, and sham-EA (non-acupoint) groups, with 12 rats in each group. The hypertension model was established by occlusion of the right renal aorta (two-kidney-one clip method). Rats of the sham-operation group received the same surgery but without occlusion of the renal artery. EA (2 Hz/15 Hz, 2 mA) was applied to bilateral LR3 for 30 min, once a day for 28 days, and sham EA was applied to the skin of the rat tail near the buttock on both sides. The mean arterial pressure (MAP) of the abdominal aorta and heart rate (HR) were recorded. The autonomic nerve function was assessed by using frequency domain analysis of heart rate variability (HRV), and the baroreflex sensitivity detected by sequential method. Plasma norepinephrine (NE) level was measured by ELISA, and the α2AR positive neurons and α2AR protein expression in NTS were detected by using fluorescence immunohistochemistry and Western blot, respectively. The functions of α2AR within the NTS in modulating MBP and HR were verified by microinjection of its agonist (clonidine) and antagonist (yohimbine) separately. RESULTS: Compared to the sham operation rats, the hypertension rats displayed significant increases in the MAP (P<0.01), plasma norepinephrine content (P<0.01), ratios of low frequency/total power (LF/TP) and low frequency/high frequency (LF/HF) (P<0.01), and significant reduction in the overall gain, uplink sequence gain and downlink sequence gain of baroreflex (P<0.01), the number α2AR positive neurons and α2AR protein expression level in NTS (P<0.01). The rats in the EA group (rather than in the sham-EA group) showed significant reduction in MAP at the 3rd and 4th week, plasma NE content, LF/TP and LF/HF (P<0.01), and obvious increase in the overall gain, uplink sequence gain and downlink sequence gain of baroreflex (P<0.01), and the number of α2AR positive neurons and α2AR protein expression in comparison (P<0.05) with those of the model group. Microinjection of clonidine into NTS induced an evident decrease in both MAP and HR in the model group relevant to the sham operation group (P<0.01), while the MAP and HR changes of the EA (not sham EA) group were considerably bigger than those of the model group (P<0.05), being similar to those of the sham-operation group (P>0.05), which suggested an elimination of the BP-lowering effect of clonidine after EA. CONCLUSION: EA at LR3 can reduce MBP, sympathetic activities, improve baroreflex sensitivity in renovascular hypertensive rats, which may be associated with its effects in up-regulating the decreased NTS α2AR expression and functional activities.


Assuntos
Eletroacupuntura , Hipertensão , Animais , Barorreflexo , Hipertensão/genética , Hipertensão/terapia , Masculino , Ratos , Ratos Sprague-Dawley , Receptores Adrenérgicos , Núcleo Solitário
5.
Biomaterials ; 271: 120736, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33662745

RESUMO

The reduced coenzymes (NADH and NADPH) are an important product in energy metabolism and closely related to the occurrence and development of cancer. So it is necessary to use a powerful detection tool to visualize NAD(P)H in energy metabolism of tumor cells and find a new strategy to improve cancer treatment based on NAD(P)H. Herein, a novel multifunctional probe (Cy-N) is synthesized with good near-infrared fluorescence (NIRF) response to NAD(P)H and the photoacoustic (PA) and photothermal properties are successfully activated by NAD(P)H. The probe is successfully applied in visualizing NAD(P)H in energy metabolism of tumor cells and imaging NAD(P)H in bacteria. Moreover, the probe can be used to image NAD(P)H in energy metabolism of tumor-bearing mice by dual-modal imaging (NIRF and PA). More importantly, in terms of the role of NAD(P)H in energy metabolism, the photothermal therapy (PTT) is activated by NAD(P)H and a novel strategy of enhanced PTT is proposed by injecting glucose. As far as we know, this is the first probe to detect NAD(P)H in energy metabolism through dual-modal imaging, and also the first probe to activate PTT based on NAD(P)H, which will provide important information of the diagnosis and treatment of cancer.

6.
Sci Total Environ ; 777: 146180, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33689891

RESUMO

This paper investigates the impacts of extensive riverbed mining in the Lower Mekong on the water level, extent and volume of the Tonlé Sap Lake, the largest freshwater lake in Southeast Asia. Our results indicate that the lake's volume has decreased from 1980 to 2018 (p-value = 0.016), with water levels at Phnom Penh Port and Phnom Penh Bassac showing decreasing trends since 1980 (p-values <0.0001). However, discharge at Phnom Penh Bassac (1960-2002) presented an insignificant trend (p-value = 0.147), indicating that riverbed incision due to extensive sand mining in Phnom Penh has affected the Mekong's water levels more than basin-scale climatic factors. Similarly, the modulation of a limited portion of water by upstream dams is unlikely to have caused dramatic inundation variation along the Lower Mekong River around Tonlé Sap. A hysteretic relationship between water levels at Prek Kdam and Tonlé Sap indicates that Tonlé Sap's water level is largely controlled by Tonlé Sap River and the Mekong, and declining water levels at Prek Kdam due to extensive sand mining in Phnom Penh is directly related to the shrinking of the lake. Although there are three main inflows into Tonlé Sap (from the Mekong, local tributaries and direct precipitation), the Mekong's contribution is the largest; tributary discharge and rainfall did not display any significant trend over the investigated period as well. Additionally, the analysis of high-resolution images revealed a recent intensification of riverbed mining, with Phnom Penh being a mining hotspot in the Lower Mekong. Considering its economic and ecological importance, the shrinking of Tonlé Sap would have grave repercussions for the region. Since sand demand is unlikely to weaken in the foreseeable future, these new insights can potentially help inform regulatory frameworks in ensuring sustainable sand extraction rates.

7.
J Prosthet Dent ; 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33685653

RESUMO

STATEMENT OF PROBLEM: The presence of biofilms on maxillofacial silicone increases the risk of infections and reduces durability. Whether silver nanoparticles (AgNPs) with potent antimicrobial effects help reduce biofilm formation is unclear. PURPOSE: The purpose of this in vitro study was to assess the antimicrobial effect of sub 10-nm AgNPs in maxillofacial silicone against Staphylococcus aureus, Candida albicans, and mixed species biofilms containing both and to test the effectiveness of different AgNP concentrations against all 3 biofilms in vitro. MATERIAL AND METHODS: Silicone disks (M511; Technovent Ltd) containing 0.0% (control), 0.1%, and 0.5% AgNPs were fabricated and treated with S. aureus, C. albicans, and mixed species strains of both in 24-well culture plates containing appropriate media. Each well received a 0.1-mL aliquot of the standardized suspension of microorganisms. The plates were incubated for 21 consecutive days, and colony-forming units per milliliter (CFU/mL) were measured on the first, third, fifth, seventh, fifteenth, and twenty-first day with the Miles and Misra method. Data were analyzed by 2-way ANOVA and the paired t test to evaluate the relationship between AgNP concentration, microbial strain, and time (α=.05). Mean CFU/mL differences for each time and for each biofilm category were assessed by repeated measure ANOVA. RESULTS: AgNPs decreased the mean CFU/mL in both concentrations compared with the control. The 0.1% concentration showed sustained efficacy throughout the test, while the 0.5% concentration had high efficacy initially with a gradual decrease. However, the results were inconsistent for the mixed biofilm. The paired sample t test at day 3 and 15 and day 3 and 21 showed statistically significantly different results (P<.001) in all but 1 group in the 0.5% concentration. The 2-way mixed ANOVA showed statistically significant (P<.001) interaction between AgNP concentration and time in all groups. The 1-way ANOVA of AgNP concentrations was statistically significantly different (P<.001) for all time points. A statistically significant (P<.001) effect of time on CFU/mL was found for all the AgNP concentration groups in all 3 biofilms. CONCLUSIONS: Silicone elastomers with sub 10-nm AgNPs displayed antimicrobial properties in vitro against S. aureus, C. albicans, and mixed species strains. AgNPs (0.1%) were effective against both microbial strains and can provide a baseline for further long-term studies regarding antimicrobial efficacy, silver ion leaching, and cellular internalization. Mixed species biofilm needs further exploration with standardized study parameters.

8.
J Agric Food Chem ; 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33787231

RESUMO

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) is an effective target for green herbicide discovery. In this work, we reported the unexpected discovery of a novel series of N-phenylaminomethylthioacetylpyrimidine-2,4-diones (2-6) as promising PPO inhibitors based on investigating the reaction intermediates of our initially designed N-phenyluracil thiazolidinone (1). An efficient one-pot procedure that gave 41 target compounds in good to high yields was developed. Systematic Nicotiana tabacum PPO (NtPPO) inhibitory and herbicidal activity evaluations led to identifying some compounds with improved NtPPO inhibition potency than saflufenacil and good post-emergence herbicidal activity at 37.5-150 g of ai/ha. Among these analogues, ethyl 2-((((2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-(trifluoromethyl)-3,6-dihydropyrimidin-1(2H)-yl)phenyl)amino)methyl)thio)acetate (2c) (Ki = 11 nM), exhibited excellent weed control at 37.5-150 g of ai/ha and was safe for rice at 150 g of ai/ha, indicating that compound 2c has the potential to be developed as a new herbicide for weed management in paddy fields. Additionally, our molecular simulation and metabolism studies showed that the side chains of compound 2c could form a hydrogen-bond-mediated seven-membered ring system; substituting a methyl group at R1 could reinforce the hydrogen bond of the ring system and reduce the metabolic rate of target compounds in planta.

9.
Biomolecules ; 11(2)2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33671480

RESUMO

The resurrection plants Myrothamnus flabellifolia can survive long term severe drought and desiccation conditions and soon recover after rewatering. However, few genes related to such excellent drought tolerance and underlying molecular mechanism have been excavated. WRKY transcription factors play critical roles in biotic and abiotic stress signaling, in which WRKY70 functions as a positive regulator in biotic stress response but a negative regulator in abiotic stress signaling in Arabidopsis and some other plant species. In the present study, the functions of a dehydration-induced MfWRKY70 of M. flabellifolia participating was investigated in the model plant Arabidopsis. Our results indicated that MfWRKY70 was localized in the nucleus and could significantly increase tolerance to drought, osmotic, and salinity stresses by promoting root growth and water retention, as well as enhancing the antioxidant enzyme system and maintaining reactive oxygen species (ROS) homeostasis and membrane-lipid stability under stressful conditions. Moreover, the expression of stress-associated genes (P5CS, NCED3 and RD29A) was positively regulated in the overexpression of MfWRKY70 Arabidopsis. We proposed that MfWRKY70 may function as a positive regulator for abiotic stress responses and can be considered as a potential gene for improvement of drought and salinity tolerance in plants.

10.
Eur Radiol ; 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33758954

RESUMO

OBJECTIVE: The study aimed to evaluate the predictive validity of the neural network (NN) method for presurgical mapping of motor areas using resting-state functional MRI (rs-fMRI) data of patients with brain tumor located in the perirolandic cortex (PRC). METHODS: A total of 109 patients with brain tumors occupying PRC underwent rs-fMRI and hand movement task-based fMRI (tb-fMRI) scans. Using a NN model trained on fMRI data of 47 healthy controls, individual task activation maps were predicted from their rs-fMRI data. NN-predicted maps were compared with task activation and independent component analysis (ICA)-derived maps. Spatial Pearson's correlation coefficients (CC) matrices and Dice coefficients (DC) between task activation and predicted activation using NN (DCNN_Act) and ICA (DCICA_Act) were calculated and compared using non-parametric tests. The effects of tumor types and head motion on predicted maps were demonstrated. RESULTS: The CC matrix of NN-predicted maps showed higher diagonal values compared with ICA-derived maps (p < 0.001). DCNN_Act were higher than DCICA_Act (p < 0.001) for patients with or without motor deficits. Lower DCs were found in subjects with head motion greater than one voxel. DCs were higher on the nontumor side than on the tumor side (p < 0.001), especially in the glioma group compared with meningioma and metastatic groups. CONCLUSIONS: This study indicated that the NN approach could predict individual motor activation using rs-fMRI data and could have promising clinical applications in brain tumor patients with anatomical and functional reorganizations. KEY POINTS: • The neural network machine learning approach successfully predicted hand motor activation in patients with a tumor in the perirolandic cortex, despite space-occupying effects and possible functional reorganization. • Compared to the conventional independent component analysis, the neural network approach utilizing resting-state fMRI data yielded a higher correlation to the active task hand activation data. • The Dice coefficient of machine learning-predicted activation vs. task fMRI activation was different between tumor and nontumor side, also between tumor types, which might indicate different effects of possible neurovascular uncoupling on resting-state and task fMRI.

11.
Proc Natl Acad Sci U S A ; 118(13)2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33753520

RESUMO

Protein stability affects the physiological functions of proteins and is also a desirable trait in many protein engineering tasks, yet improving protein stability is challenging because of limitations in methods for directly monitoring protein stability in cells. Here, we report an in vivo stability biosensor wherein a protein of interest (POI) is inserted into a microbial enzyme (CysGA) that catalyzes the formation of endogenous fluorescent compounds, thereby coupling POI stability to simple fluorescence readouts. We demonstrate the utility of the biosensor in directed evolution to obtain stabilized, less aggregation-prone variants of two POIs (including nonamyloidogenic variants of human islet amyloid polypeptide). Beyond engineering applications, we exploited our biosensor in deep mutational scanning for experimental delineation of the stability-related contributions of all residues throughout the catalytic domain of a histone H3K4 methyltransferase, thereby revealing its scientifically informative stability landscape. Thus, our highly accessible method for in vivo monitoring of the stability of diverse proteins will facilitate both basic research and applied protein engineering efforts.

12.
Anal Chem ; 93(8): 4118-4125, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33586951

RESUMO

Shape selectivity is important in reversed-phase liquid chromatographic separations, where stationary phases are capable of separating geometric isomers, thereby resolving solutes based on their three-dimensional structure or shape rather than other chemical differences. Numerous chromatographic studies have been carried out using n-alkyl-chain-modified columns to understand how molecular shape affects retention. For polycyclic aromatic hydrocarbons (PAHs), it was found that planar compounds were selectively retained over nonplanar structures of comparable molecular weight on surfaces with longer n-alkyl chains, higher chain-density, or at lower temperatures, where selectivity likely arises with greater ordering of the n-alkyl chains. A limitation of these studies, however, is the small range of chain ordering that can be achieved and lack of a direct measure of the n-alkyl-chain order of the stationary phases. In this work, we employ a C18 stationary phase modified with a monolayer of phospholipid as a means of significantly varying the n-alkyl chain order. These hybrid-supported lipid bilayers, which have previously been employed as membrane-like stationary phases for measuring lipophilicity, provide a unique approach to control n-alkyl chain ordering by varying the acyl chain length and degree of unsaturation of the phospholipid modifier. The degree of alkyl-chain order of the resulting modified surfaces is determined from the ratio of trans- versus gauche-conformers, measured in situ within individual porous particles by confocal Raman microscopy. This methodology was also used to assess the affinity of these surfaces for planar versus nonplanar PAH molecules. The retention selectivity for the planar versus nonplanar compounds, thus determined, was found to vary significantly and systematically with the degree of order of the acyl/alkyl chains in the hybrid-supported lipid bilayers. The investigation also demonstrates the utility of confocal Raman microscopy for interrogating the impact of solute partitioning on stationary-phase structure within porous chromatographic particles.

13.
Cell Death Dis ; 12(2): 221, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33637683

RESUMO

Gastric mucosal injury is a less well known complication of obesity. Its mechanism remains to be further elucidated. Here, we explored the protective role of lipocalin 2 (LCN2) against endoplasmic reticulum stress and cell apoptosis in gastric mucosa in patients and mice with obesity. Through molecular and genetic analyses in clinical species, LCN2 secreted by parietal cells expression is elevated in obese. Immunofluorescence, TUNEL, and colorimetry results show that a more significant upregulation of pro-inflammatory factors and increased amount of apoptotic cells in gastric tissue sections in obese groups. Loss- and gain-of-function experiments in gastric epithelial cells demonstrate that increased LCN2 protected against obesity associated gastric injury by inhibiting apoptosis and improving inflammatory state. In addition, this protective effect was mediated by repressing ER stress. Our findings identify LCN2 as a gastric hormone could be a compensatory protective factor against gastric injury in obese.

14.
J Chromatogr A ; 1640: 461946, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33556682

RESUMO

In previous work, we have established a one-step method to immobilize halo-tagged proteins onto microspheres through the covalent bond formed between the halo-tag and the halide linkers on the support surface. We observe extremely tailed peaks of most of drugs on the immobilized proteins, which is reasoned by the nonspecific interaction between the linkers and the drugs. To prove this, the current work designed five different halide linkers for the immobilization of beta2-adrenoceptor (ß2-AR). We applied the immobilized receptor to systematically realize the effects of these halide linkers on drug-receptor interaction by analyzing peak profiles of five drugs. The retention times and the half-widths of the drugs appeared to be negatively correlated to the atom numbers of the linkers in the range of 6-13 atoms. Subsequent increase of linker atoms resulted in reduced retention times and wider peaks of the drugs. Applying identical linker length, we observed clear reduced retention times and half-widths of the five drugs than the linker in the absence of oxygen atom. Such improvement was dominated by the number of oxygen atoms. These indicated that linker S-4 (2-(2-(2-(2-chloroethoxy) ethoxy) ethoxy) acetic acid) was optimal to eliminate the unwanted non-specific interactions. In comparison with the columns prepared by linker S-1 (6-chlorocaproic acid) and histidine tagged ß2-AR, the drugs on the linker S-4 column gave greater dissociation rate constants (e.g. 60.3±0.3 s-1 for salbutamol), which is closer to the data in literatures. Taking together, we concluded that optimization of the linker structure plays particular role in reducing the non-specific interaction between the immobilized protein and the drugs, thereby making the determination of drug-protein interaction more reliable.


Assuntos
Halogênios/química , Proteínas Imobilizadas/química , Preparações Farmacêuticas/química , Cromatografia de Afinidade , Histidina/química , Cinética , Dinâmica não Linear , Receptores Adrenérgicos beta 2/química , Fatores de Tempo
15.
Anal Chem ; 93(6): 3301-3307, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33535747

RESUMO

Diabetes is one of the metabolic diseases marked by hyperglycemia and is often accompanied by the occurrence of some complications. As a biomarker of oxidative stress, hydrogen peroxide (H2O2) has close association with the occurrence and development of diabetes and its complications. Unfortunately, there is no fluorescent probe reported for imaging H2O2 in diabetic mice. Here, a novel near-infrared (NIR) fluorescent probe named QX-B was designed and synthesized to detect H2O2. For the probe, the quinolinium-xanthene dye is used as the fluorophore and borate ester is chosen as the response group. After the addition of H2O2, a strong NIR fluorescence signal at 772 nm is observed. The probe not only shows high sensitivity with 10-fold enhancement but also displays excellent selectivity to H2O2 over other possible interfering species. In the meantime, the possible response mechanism of QX-B toward H2O2 was proposed and verified by the high-performance liquid chromatography (HPLC) experiment, mass spectra (MS) experiment, and density functional theory (DFT) calculation. Furthermore, based on the low cell cytotoxicity of QX-B, it has been applied in imaging exogenous and endogenous H2O2 in HeLa cells, HCT116 cells, 4T1 cells, and zebrafish successfully. More importantly, inspired by the performance of NIR fluorescence, QX-B has been used in monitoring H2O2 in diabetic mice for the first time. This provides very important information for the diagnosis and treatment of diabetes and its complications.

16.
Cell ; 184(4): 943-956.e18, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33571432

RESUMO

Dopamine receptors, including D1- and D2-like receptors, are important therapeutic targets in a variety of neurological syndromes, as well as cardiovascular and kidney diseases. Here, we present five cryoelectron microscopy (cryo-EM) structures of the dopamine D1 receptor (DRD1) coupled to Gs heterotrimer in complex with three catechol-based agonists, a non-catechol agonist, and a positive allosteric modulator for endogenous dopamine. These structures revealed that a polar interaction network is essential for catecholamine-like agonist recognition, whereas specific motifs in the extended binding pocket were responsible for discriminating D1- from D2-like receptors. Moreover, allosteric binding at a distinct inner surface pocket improved the activity of DRD1 by stabilizing endogenous dopamine interaction at the orthosteric site. DRD1-Gs interface revealed key features that serve as determinants for G protein coupling. Together, our study provides a structural understanding of the ligand recognition, allosteric regulation, and G protein coupling mechanisms of DRD1.

17.
Comput Med Imaging Graph ; 88: 101845, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33582593

RESUMO

Accurate and early diagnosis is critical to proper malaria treatment and hence death prevention. Several computer vision technologies have emerged in recent years as alternatives to traditional microscopy and rapid diagnostic tests. In this work, we used a deep learning model called Mask R-CNN that is trained on uninfected and Plasmodium falciparum-infected red blood cells. Our predictive model produced reports at a rate 15 times faster than manual counting without compromising on accuracy. Another unique feature of our model is its ability to generate segmentation masks on top of bounding box classifications for immediate visualization, making it superior to existing models. Furthermore, with greater standardization, it holds much potential to reduce errors arising from manual counting and save a significant amount of human resources, time, and cost.

18.
Endocr Pract ; 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33601024

RESUMO

OBJECTIVE: Owing to limited research, the effect of non-alcoholic fatty liver disease (NAFLD) on type 2 diabetes outcomes remains unclear. This study aimed to investigate the association between NAFLD and microvascular complications in hospitalized patients with type 2 diabetes. METHODS: We included 1982 patients with type 2 diabetes. NAFLD was defined as hepatic steatosis detected by ultrasound without secondary causes of fat accumulation. The diagnosis of diabetic retinopathy (DR), diabetic kidney disease (DKD) and diabetic neuropathy was based on clinical medical records. Risk for advanced liver fibrosis was categorized as "low risk," "indeterminate risk," and "high risk," based on the NAFLD Fibrosis Score (NAFLD-FS). Logistic regression was used to test the association between NAFLD, risk for advanced fibrosis and the presence of DR, DKD, and diabetic neuropathy. RESULTS: The prevalence of NAFLD was 61.3%. The presence of DR (odds ratio [OR]: 0.749, 95% confidence interval [CI]: 0.578-0.971), and DKD (OR: 0.667, 95% CI: 0.515-0.864) was inversely associated with NAFLD, after adjusting for covariates. The presence of DR and DKD was higher in the "indeterminate risk" (DR: OR: 1.237, 95% CI: 0.730-2.096; DKD: OR: 1.009, 95% CI: 0.640-1.591, respectively) and "high risk" group (DR: OR: 1.341, 95% CI: 0.730-2.463; DKD: OR: 1.732, 95% CI: 1.021-2.940, respectively) than in the "low risk" group, after adjusting for the same covariates. Only the presence of DKD significantly increased with high NAFLD-FS (P=0.01 for trend). CONCLUSION: The presence of DR and DKD was inversely associated with NAFLD among hospitalized patients with type 2 diabetes. DKD was closely associated with high NAFLD-FS among patients with NAFLD.

20.
Carbohydr Polym ; 257: 117642, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33541666

RESUMO

Carrageenan (CRG) is a kind of linear sulfated polysaccharide that emerging as a promising substituent in food, pharmaceutics, and cosmetics. In recent years, biological properties of CRG polysaccharides such as antiviral, immunomodulatory, anticoagulant, antioxidant, and anticancer have been broadly studied, however, systematical summary of their structure-property relationships is scarce. Moreover, chemical modification is of great significance to explore biological and physiochemical properties of CRG polysaccharides which should be focused on. Chemical modification of CRG polysaccharides, e.g., carboxymethylation, thiolation, acetylation, phosphorylation, oversulfation, oxidization, and cationic or other derivatives, can improve their bioactivities and facilitate their applications in different biological systems. Hence, this review aims to elucidate structure-property relationships of CRG and its chemically modified derivatives with different structures and bioactivities, so as toxicity of CRG as food additive for the guidance of its clinical application.

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