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1.
Bioact Mater ; 19: 348-359, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35892002

RESUMO

Cardiac extracellular matrices (ECM) play crucial functional roles in cardiac biomechanics. Previous studies have mainly focused on collagen, the major structural ECM in heart wall. The role of elastin in cardiac mechanics, however, is poorly understood. In this study, we investigated the spatial distribution and microstructural morphologies of cardiac elastin in porcine left ventricles. We demonstrated that the epicardial elastin network had location- and depth-dependency, and the overall epicardial elastin fiber mapping showed certain correlation with the helical heart muscle fiber architecture. When compared to the epicardial layer, the endocardial layer was thicker and has a higher elastin-collagen ratio and a denser elastin fiber network; moreover, the endocardial elastin fibers were finer and more wavy than the epicardial elastin fibers, all suggesting various interface mechanics. The myocardial interstitial elastin fibers co-exist with the perimysial collagen to bind the cardiomyocyte bundles; some of the interstitial elastin fibers showed a locally aligned, hinge-like structure to connect the adjacent cardiomyocyte bundles. This collagen-elastin combination reflects an optimal design in which the collagen provides mechanical strength and elastin fibers facilitate recoiling during systole. Moreover, cardiac elastin fibers, along with collagen network, closely associated with the Purkinje cells, indicating that this ECM association could be essential in organizing cardiac Purkinje cells into "fibrous" and "branching" morphologies and serving as a protective feature when Purkinje fibers experience large deformations in vivo. In short, our observations provide a structural basis for future in-depth biomechanical investigations and biomimicking of this long-overlooked cardiac ECM component.

2.
Food Chem ; 400: 134100, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36075172

RESUMO

Poly (butylene adipate-co-terephthalate) (PBAT)/polylactic acid (PLA) blended with compatibilizers (polycaprolactone, PCL; poly (ethylene glycol), PEG; titanium dioxide, nano-TiO2) (TP@PLA composites) were developed by melt processing. Natamycin incorporated into TP@PLA blend composites formed NTP@PLA films, which exhibited high tensile strength (24.1-43.5 MPa) and elongation at break (85.8-258.2 %), and exhibited good oxygen permeability, water vapor permeability, surface hydrophobicity and biodegradability. The in vitro results revealed that inhibition of Penicillium expansum cell growth of the NTP@PLA films with addition of 1.0 wt% natamycin reached 95.72 %. The NTP@PLA film with natamycin effectively reduced incidence of decay (1.52 %) on grapes, maintained their quality, and inhibited the growth of pathogenic fungi to up to 0.42 log cfu·g-1. This study generates new insights into the preservation properties of antimicrobial NTP@PLA film, which endow it with great application potential as a novel and eco-friendly packaging material for the food industry.

3.
J Interv Cardiol ; 2022: 3932912, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35360092

RESUMO

Background: The combined procedure of left atrial appendage closure (LAAC) and catheter ablation (CA) is a safe and feasible therapy to treat patients with atrial fibrillation (AF). However, the effect of the combined procedure on cardiac function remains unclear. This study aimed to investigate the changes in endocrine and mechanical function of the heart following the combined procedure. Methods: This retrospective study included 62 consecutive patients who underwent the combined procedure of AF ablation and WATCHMAN LAAC and 62 sex and age-matched patients who only received AF ablation. During follow-up, patients were examined for brain natriuretic peptide (BNP) levels to represent endocrine cardiac function. Mechanical cardiac function was assessed during echocardiographic examination by means of the LA ejection fraction, LA strain (Ƹ), and LA strain rate (SR). Results: (1) The BNP levels decreased acutely after the procedure, rose at day 3 postoperation, but trended downwards at 3 months postoperation in both groups. No significant difference was observed between the two groups. (2) LA ejection fraction, LA Ƹ, and SR exhibited a continuous upward trend over a 3-month follow-up in both groups. There was no significant difference in LA ejection fractions, SRe (the parameter of LA conduit function), and SRa (the parameter of LA booster pump function) between the two groups. However, the Ƹ and SRs (the parameters of LA reservoir function) improved in patients treated with CA alone. Conclusions: The combined procedure of LAAC and CA significantly improved the endocrine and mechanical function of the heart. Compared to simple CA, based on CA with LAAC intervention, it does not significantly change LA endocrine function but may lead to a decline in the LA reservoir function.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Ablação por Cateter , Apêndice Atrial/diagnóstico por imagem , Apêndice Atrial/cirurgia , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Humanos , Estudos Retrospectivos , Resultado do Tratamento
4.
Proteome Sci ; 20(1): 14, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36071491

RESUMO

BACKGROUND: Citrate Synthase (Cs) gene mutation (locus ahL4) has been found to play an important role in progressive hearing loss of A/J mice. HEI-OC1 cells have been widely used as an in vitro system to study cellular and molecular mechanisms related to hearing lose. We previously reported the increased apoptosis and the accumulation of reactive oxygen species in shRNACs-1429 cells, a Cs low-expressed cell model from HEI-OCI. The details of the mechanism of ROS production and apoptosis mediated by the abnormal expression of Cs needed to research furtherly. METHODS: iTRAQ proteomics was utilized to detect the differentially expressed proteins (DEPs) caused by low expression of Cs. The GO and KEGG pathways analysis were performed for annotation of the differentially expressed proteins. Protein-protein interaction network was constructed by STRING online database. Immunoblotting was utilized to confirm the protein levels of the the differentially expressed proteins. RESULTS: The differentially expressed proteins were significantly enriched in various signaling pathways mainly related to mitochondrial dysfunction diseases including Parkinson's disease, Alzheimer's disease, Huntington's disease, et al. Most noteworthy, the oxidative phosphorylation pathway was most significantly suppressed in the shRNACs-1429 cells,, in which a total of 10 differentially expressed proteins were enriched and were all downregulated by the abnormal expression of Cs. The downregulations of Ndufb5, Ndufv1 and Uqcrb were confirmed by immunoblotting. Meanwhile, the ATP levels of shRNACs-1429 cells were also reduced. CONCLUSIONS: These results suggest that low level expression of Cs induces the inhibition of oxidative phosphorylation pathway, which is responsible for the high level production of reactive oxygen species and low level of ATP, leading to the apoptosis of cochlear cells. This study may provide new theories for understanding and therapy of progressive hearing loss.

5.
Cell Stem Cell ; 29(9): 1402-1419.e8, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36055194

RESUMO

Despite its clinical and fundamental importance, our understanding of early human development remains limited. Stem cell-derived, embryo-like structures (or embryoids) allowing studies of early development without using natural embryos can potentially help fill the knowledge gap of human development. Herein, transcriptome at the single-cell level of a human embryoid model was profiled at different time points. Molecular maps of lineage diversifications from the pluripotent human epiblast toward the amniotic ectoderm, primitive streak/mesoderm, and primordial germ cells were constructed and compared with in vivo primate data. The comparative transcriptome analyses reveal a critical role of NODAL signaling in human mesoderm and primordial germ cell specification, which is further functionally validated. Through comparative transcriptome analyses and validations with human blastocysts and in vitro cultured cynomolgus embryos, we further proposed stringent criteria for distinguishing between human blastocyst trophectoderm and early amniotic ectoderm cells.


Assuntos
Camadas Germinativas , Análise de Célula Única , Animais , Blastocisto , Linhagem da Célula , Ectoderma , Embrião de Mamíferos , Humanos
7.
FEMS Microbiol Lett ; 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36073496

RESUMO

Although probiotics have been isolated from different sources, few were isolated from traditional Chinese medicine. The current study firstly isolate Pulsatilla Radix-utilizing Pediococcus pentosaceus PR-1 from human faeces. Subsequently, the tolerance of PR-1 to low pH, bile salts, simulated gastric juice and succus entericus, antioxidant activity, antimicrobial activity, cholesterol-assimilation and antibiotics susceptibility were investigated. After 2 h incubation at pH 2.0, over 80% of PR-1 survived. The cell viability of PR-1 at 2 h under 0.1% bile salt condition was 99.2%. The survival rate of PR-1 in gastric juice and succus entericus were 64.48% and 81.86, respectively. Cell-free supernatant of PR-1 culture also showed antimicrobial activity against Escherichia coli, Staphylococcus aureus, and Salmonella typhimurium. Besides, antioxidant activity of PR-1 CFS was significantly greater than cell pellet. PR-1 was shown resistant to kanamycin, streptomycin, vancomycin, and norfloxacin and able to lower cholesterol level to 72.5 ± 1.5%. In addition, PR-1 displayed γ-hemolysis and was non-pathogenic.

8.
Eur J Nutr ; 2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36056948

RESUMO

PURPOSE: Abnormal acetylation modification is a common epigenetic change in tumorigenesis and is closely related to the progression of colorectal cancer (CRC). Our previous studies have suggested that black raspberry (BRB) anthocyanins have a significant chemopreventive effect against CRC. This study investigated whether protein acetylation plays an important role in BRB anthocyanins-mediated regulation of CRC progression. METHODS: We used the AOM-induced CRC mouse model and the CRC cell lines SW480 and Caco-2 to explore the potential role of acetylation of histone H4 and NF-κB signaling pathway-related proteins (non-histone proteins) in the antitumor process mediated by BRB anthocyanins. The expression of related proteins was detected by western blot. ROS level was detected by immunofluorescence. RESULTS: BRB anthocyanins affected the acetylation level by down-regulating the expression of Sirtuin1 (SIRT1) and up-regulating the expression of MOF and EP300. The acetylation level of lysine sites on histone H4 (H4K5, H4K12 and H4K16) was increased. Furthermore, following BRB anthocyanins treatment, the expression of ac-p65 was significantly up-regulated and the NF-κB signal pathway was activated, which in turn up-regulated Bax expression and inhibited Bcl-2, cyclin-D1, c-myc and NLRP3 expression to promote CRC cell cycle arrest, apoptosis and relieve inflammation. CONCLUSION: The findings suggested that protein acetylation could play a critical role in BRB anthocyanins-regulated CRC development.

9.
J Integr Plant Biol ; 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36053143

RESUMO

Brassinosteroids (BRs) and abscisic acid (ABA) are essential regulators of plant growth and stress tolerance. Although the antagonistic interaction of BRs and ABA is proposed to ensure the balance between growth and defense in model plants, the crosstalk between BRs and ABA in response to chilling in tomato (Solanum lycopersicum), a warm-climate horticultural crop, is unclear. Here, we determined that overexpression of the BR biosynthesis gene DWARF (DWF) or the key BR signaling gene BRASSINAZOLE-RESISTANT1 (BZR1) increases ABA levels in response to chilling stress via positively regulating the expression of the ABA biosynthesis gene 9-CIS-EPOXYCAROTENOID DIOXYGENASE1 (NCED1). BR-induced chilling tolerance was mostly dependent on ABA biosynthesis. Chilling stress or high BR levels decreased the abundance of BRASSINOSTEROID-INSENSITIVE2 (BIN2), a negative regulator of BR signaling. Moreover, we observed that chilling stress increases BR levels and results in the accumulation of BZR1. BIN2 negatively regulated both the accumulation of BZR1 protein and chilling tolerance by suppressing ABA biosynthesis. Our results demonstrate that BR signaling positively regulates chilling tolerance via ABA biosynthesis in tomato. The study has implications in production of warm-climate crops in horticulture. This article is protected by copyright. All rights reserved.

10.
Transgenic Res ; 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36053433

RESUMO

Insulators in vertebrates play a role in genome architecture and orchestrate temporo-spatial enhancer-promoter interactions. In plants, insulators and their associated binding factors have not been documented as of yet, largely as a result of a lack of characterized insulators. In this study, we took a comprehensive strategy to identify and validate the enhancer-blocking insulator CW198. We show that a 1.08-kb CW198 fragment from Arabidopsis can, when interposed between an enhancer and a promoter, efficiently abrogate the activation function of both constitutive and floral organ-specific enhancers in transgenic Arabidopsis and tobacco plants. In plants, both transcriptional crosstalk and spreading of histone modifications were rarely detectable across CW198, which resembles the insulation property observed across the CTCF insulator in the mammalian genome. Taken together, our findings support that CW198 acts as an enhancer-blocking insulator in both Arabidopsis and tobacco. The significance of the present findings and their relevance to the mitigation of mutual interference between enhancers and promoters, as well as multiple promoters in transgenes, is discussed.

11.
Am J Hematol ; 2022 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-36054234

RESUMO

Cytomegalovirus (CMV) infection remains a major cause of mortality after hematopoietic stem cell transplantation (HSCT). Current treatments, including anti-viral drugs and adoptive cell therapy with CMV-specific cytotoxic T lymphocytes (CTLs),only show limited benefits in patients. T-cell receptor (TCR)-T cell therapy offers a promising option to treat CMV infections. Here, using tetramer-based screening and single-cell TCR cloning technologies, we identified various CMV antigen-specific TCRs from healthy donors, and generated TCR-T cells targeting multiple pp65 epitopes corresponding to three major HLA-A alleles. The TCR-T cells showed efficient cytotoxicity towards epitope-expressing target cells in vitro. After transfer into immune-deficient mice bearing pp65+ HLA+ tumor cells, TCR-T cells induced dramatic tumor regression and exhibited long-term persistence. In a phase I clinical trial (NCT04153279), CMV TCR-T cells were applied to treat patients with CMV reactivation after HSCT. Except one patient who withdrew at early treatment stage, all other 6 patients were well-tolerated and achieved complete response (CR), no more than grade 2 cytokine release syndrome (CRS) and other adverse events were observed. CMV TCR-T cells persisted up to 3 months. Among them, 2 patients have survived for more than one year. This study demonstrates the great potential in the treatment and prevention of CMV infection following HSCT or other organ transplantation. This article is protected by copyright. All rights reserved.

12.
Adv Mater ; : e2206486, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36047665

RESUMO

The intentionally designed band alignment of heterostructures and doping engineering are keys to implement device structure design and device performance optimization. According to the theoretical prediction of several typical materials among the TMDs and group IV metal chalcogenides, MoS2 and SnSe2 present the largest staggered band offset. The large band offset is conducive to the separation of photogenerated carriers, thus MoS2 /SnSe2 is a theoretically ideal candidate for fabricating photodetector, which is also verified in our experiment. Furthermore, in order to extend the photoresponse spectrum to solar-blind ultraviolet (SBUV), doping engineering is adopted to form an additional electron state, which provides an extra carrier transition channel. In this work, pure MoS2 /SnSe2 and doped MoS2 /SnSe2 heterostructures are both fabricated. In terms of the photoelectric performance evaluation, the rejection ratio R254 /R532 of the photodetector based on doped MoS2 /SnSe2 is five orders of magnitude higher than that of pure MoS2 /SnSe2 , while the response time is obviously optimized by 3 orders. Our results demonstrate that the combination of band alignment and doping engineering provides a new pathway for constructing SBUV photodetectors. This article is protected by copyright. All rights reserved.

13.
Biomed Pharmacother ; 153: 113420, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076542

RESUMO

Betulin is the primary anti-inflammatory component of Betula platyphylla suk. cortex (birch bark), a time-honored Traditional Chinese Medicine (TCM) for healing trauma and tissue regeneration. However, the tissue regeneration effects and underlying molecular mechanism of betulin remain unknown. Therefore, it is necessary to investigate the wound repair effects and validate the mechanism of betulin in an appropriate model. In the present study, we evaluated the effects of tissue regeneration, melanin scavenging, and reactive oxygen species (ROS) inhibition of betulin using a zebrafish model. The mechanism of target genes and pathways were confirmed using quantitative polymerase chain reaction and western blotting in vivo, while molecular docking, absorption, distribution, metabolism, excretion, and toxicity investigations in-silico were conducted. Betulin significantly promoted the regeneration of zebrafish caudal fin length and area and alleviated melanin aggregation, as well as ROS generation. The relative mRNA expression of IL-1ß, TNF-α, p38α, ERK1/2, and Caspase3, and the relative protein expression of p38α, ERK1/2, Caspase3, phosphorylated proteins of p-p38α, p-ERK1/2, and p-p65 were down-regulated following betulin administration. Meanwhile, the protein ratios of p-p38α/p38α, p-ERK/ERK, and p-p65/p65 were significantly decreased. In an in-silico study, binding affinities between betulin and P38α, ERK1, ERK2, and Caspase3, and the pharmacokinetic profile of betulin were predicted. The findings suggest that the tissue regeneration mechanism of betulin is based on the inhibition of excessive inflammatory responses, melanin aggregation, and the pro-apoptotic factor, Caspase3, during the proliferation phase via the ROS/MAPKs/NF-ĸB signaling axis. Our results suggest betulin as a potential candidate for tissue regeneration.


Assuntos
NF-kappa B , Peixe-Zebra , Animais , Melaninas , Simulação de Acoplamento Molecular , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Triterpenos , Peixe-Zebra/metabolismo
15.
Chem Biodivers ; 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36094326

RESUMO

Two new lappaconitine-type C18-diterpenoid alkaloids, named as leucostosines C (1) and D (2), together with six known compounds (3-8), were isolated from the roots of Aconitum leucostomum Worosch. Their structures were elucidated by various spectroscopic analyses, including IR, HR-ESI-MS, NMR spectra and X-ray experiments. Leucostosine C is the first diterpenoid alkaloid bearing the 7-amino group. The isolated compounds were tested for the acetylcholinesterase (AChE) inhibitory effect and neuroprotective activity, none of them showed significant activities.

16.
Artigo em Inglês | MEDLINE | ID: mdl-36094822

RESUMO

Metal halide perovskites have exhibited promising potential for practical applications such as image sensors and displays benefiting from their outstanding optoelectronic properties. However, owing to the instability of the perovskite materials, producing patterned perovskite films with adequately high quality and high precision for such practical applications poses a challenge for existing patterning methods. Herein, the lamination-assisted femtosecond laser ablation (LA-FsLA) technique was successfully applied to fabricate patterned CsPbBr3 films with sufficiently high quality and high precision. A sandwich-laminated structure (glass/CsPbBr3/glass) was introduced to avoid the impact of debris on the patterned perovskite film. As a result, arbitrarily patterned perovskite films with high quality, submicron precision, and well-defined edges were successfully prepared. Moreover, the light-emitting diodes (LEDs) based on the patterned perovskite films also exhibit good emission characteristics. This work provides a promising strategy for the fabrication of patterned perovskite films with adequately high quality and high precision toward perovskite-based optoelectronic devices.

17.
Adv Mater ; : e2207445, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36094887

RESUMO

Quasi-two-dimensional (quasi-2D) perovskites have emerged as a promising luminescent material for perovskite light-emitting diodes (Pe-LEDs). However, efficiency and stability are still obstacles to practical application due to numerous defects and inefficient energy transfer of perovskite film. Herein, we firstly introduced functional phenethylammonium bromine modified CsPbBr3 nanocrystals (PEA-CsPbBr3 NCs) as multifunctional additive to simultaneously improve above-mentioned problems. PEA-CsPbBr3 NCs not only serves as hetero-nuclear seeds and triggers growth, thus greatly reducing leakage current, but also deliver Cs+ and Br- to passivate the intrinsic defects inside film. More importantly, PEA-CsPbBr3 construct one new carrier transfer pathway from small-n phase of quasi-2D perovskite to PEA-CsPbBr3 , which not only accelerates the energy transfer process but also promote radiation recombination of carriers due to stronger quantum confinement effect. Afterward, the PEDOT: PSS/TFB: black phosphorus QDs (BPQDs) double hole transport layer (HTL) is successfully constructed to enhance its carrier injection and charge transport abilities. Consequently, a champion external quantum efficiency of 25.32% and maximal brightness of 128842 cd/m2 , which is the record efficiency of the quasi-2D Pe-LED with pure green emission at 530 nm. Moreover, an impressive 174 min lifetime was obtained at T50 , which is about 5 times longer than the control device. This article is protected by copyright. All rights reserved.

18.
Foods ; 11(17)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36076847

RESUMO

Effects of ball milling (BM) on the structure and physicochemical properties of three types of citrus fibers were investigated. With the extension of the grinding time, the particle size of citrus fibers significantly decreased. Fourier transform infrared spectroscopy (FTIR) showed that the three citrus fibers had similar chemical groups, and more -OH and phenolic acid groups were exposed after BM, and pectin and lignin were not degraded. Scanning electron microscope (SEM) results showed that the appearance of particles changed from spherical to fragmented, irregular shapes. The water holding capacity (WHC), oil holding capacity (OHC), and water swelling capacity (WSC) of citrus fibers LM, JK, and FS reached the maximum value after BM of 2 h (increasing by 18.5%), 4 h (increasing by 46.1%), and 10 h (increasing by 38.3%), respectively. After 10 h BM, citrus fibers FS and JK had the highest adsorption capacity of cholesterol and sodium cholate, increasing by 48.3% and 48.6%, respectively. This indicates that BM transforms the spatial structure of citrus fibers and improves their physicochemical properties.

19.
Chemosphere ; : 136461, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36122752

RESUMO

Because of the current COVID-19 outbreak all over the world, the problem of antiviral drugs entering water has become increasingly serious. Arbidol hydrochloride (ABLH) is one of the most widely used drugs against COVID-19, which has been detected in sewage treatment plant sediments after the COVID-19 outbreak. However, there has been no report on the degradation of ABLH. In order to remove ABLH we prepared a novel photocatalyst composed of Ti3C2 MXene and supramolecular g-C3N4 (TiC/SCN) via a simple method. The properties of the material were studied by a series of characterizations (SEM, TEM, EDS, XRD, FTIR, UV-vis, DRS, XPS, TPC, PL, EIS and UPS), indicating the successful preparation of TiC/SCN. Results show that 99% of ABLH was removed within 150 min under visible light illumination by the 0.5TiC/SCN (containing 0.5% of TiC). The performance of 0.5TiC/SCN was about 2.66 times that of SCN resulting from the formation of Schottky junction. Furthermore, under real sunlight illumination, 99.2% of ABLH could be removed by 0.5TiC/SCN within 120 min, which was better than that of commercial P25 TiO2. The pH, anions (NO3- and SO42-) and dissolved organic matter (fulvic acid) could significantly affect the ABLH degradation. Moreover, three possible degradation pathways of ABLH were proposed, and the toxicities of the corresponding by-products were less toxic than ABLH. Meanwhile, findings showed that the superoxide radicals played a major role in the photocatalytic degradation of ABLH by 0.5TiC/SCN. This study provides a well understanding of the mechanism of ABLH degradation and provides a valuable reference for the treatment of ABLH in water.

20.
Drug Des Devel Ther ; 16: 2967-2980, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36097559

RESUMO

Background: Sotagliflozin (LX4211) is a dual inhibitor of sodium-glucose cotransporter (SGLT)1 and SGLT2 being investigated to improve glycemic control in adults with diabetes. This study was firstly conducted to assess the pharmacokinetic (PK), pharmacodynamic (PD) profiles, safety and tolerability in Chinese healthy subjects after administration of sotagliflozin. Methods: This was a Phase I, randomized, double-blind, placebo-controlled, ascending multiple-dose study. Healthy subjects received 200mg or 400mg of sotagliflozin or placebo once daily for 8 days, respectively. PK parameters of sotagliflozin and LX4211-GLU (main metabolite), as measured by blood samples collected pre/postdose on Day 1/predose on Day 2-Day 8/postdose on Day 8, and PD parameters of absolute urinary glucose excretion (UGE) were determined. Treatment-emergent adverse events (TEAEs) were evaluated. Results: Overall, 24 subjects were enrolled and randomized to sotagliflozin 200 mg (N = 9), sotagliflozin 400 mg (N = 9), or placebo (N = 6) group, and all subjects completed the study. Sotagliflozin was rapidly absorbed with dose-proportional systemic exposure and a moderate degree (less than 2-fold) of accumulation. Sotagliflozin plasma concentrations peaked at 1.0 h post dose. On Day 8, the estimated increases for Cmax and AUCtau were 1.89-fold and 1.70-fold. The pooled accumulation ratio of sotagliflozin was 1.57 for Cmax and 1.84 for AUCtau. LX4211-GLU had similar PK features. UGE was significantly elevated in both sotagliflozin groups relative to the placebo group. All TEAEs were mild and resolved without sequelae. There were no serious AEs or other significant TEAEs. Conclusion: Sotagliflozin was rapidly absorbed with dose-proportional systemic exposure and a moderate degree of accumulation. Both 200 mg and 400 mg sotagliflozin per day were well tolerated in Chinese healthy subjects.


Assuntos
Diabetes Mellitus Tipo 1 , Adulto , Glicemia/metabolismo , China , Diabetes Mellitus Tipo 1/tratamento farmacológico , Glicosídeos , Voluntários Saudáveis , Humanos
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