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1.
Diabetes Metab ; : 101318, 2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-35017100

RESUMO

PURPOSE: Type 2 diabetes (T2D) is an important risk factor for glaucoma, and sodium-glucose co-transporter 2 (SGLT2) inhibitors have been shown to protect the optic nerves. We therefore aimed to evaluate the association between SGLT2 inhibitors and incident glaucoma. METHODS: This retrospective cohort study analyzed the largest multi-institutional electronic medical records database in Taiwan, containing data of over a million individuals. We included T2D patients newly prescribed SGLT2 inhibitors or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) from 2016 to 2018. Our primary outcome was incident glaucoma diagnosis between initiation of SGLT2 inhibitors or GLP-1 RAs, and 31st March 2021. After applying inverse probability of treatment weighting (IPTW) to increase homogeneity between the two treatment groups, we estimated hazard ratios (HR) with 95% confidence intervals (CI) for the risk of glaucoma, based on Cox proportional hazards regression models. RESULTS: We included 9,927 and 1,065 T2D patients who had been newly prescribed SGLT2 inhibitors or GLP-1 RAs, respectively. Lower risk of incident glaucoma was observed in patients receiving SGLT2 inhibitors (7.9 events per 1,000 person-years), compared to those receiving GLP-1 RAs (10.0 events per 1,000 person-years), with an HR of 0.81 (95% CI: 0.69-0.95). Multiple sensitivity analyses and a negative control outcome analysis confirmed the robustness of our main findings. CONCLUSION: This study suggests that T2D patients newly prescribed SGLT2 inhibitors have a reduced risk of incident glaucoma, compared to those prescribed GLP-1 RAs, in clinical practice. Future prospective studies are suggested to confirm this association.

2.
Neural Plast ; 2022: 9941832, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35035474

RESUMO

Background: Visual symptoms are common in patients with migraine, even in interictal periods. The purpose was to assess the association between dynamic functional connectivity (dFC) of the visual cortex and clinical characteristics in migraine without aura (MwoA) patients. Methods: We enrolled fifty-five MwoA patients as well as fifty gender- and age-matched healthy controls. Regional visual cortex alterations were investigated using regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF). Then, significant regions were selected as seeds for conducting dFC between the visual cortex and the whole brain. Results: Relative to healthy controls, MwoA patients exhibited decreased ReHo and ALFF values in the right lingual gyrus (LG) and increased ALFF values in the prefrontal cortex. The right LG showed abnormal dFC within the visual cortex and with other core brain networks. Additionally, ReHo values for the right LG were correlated with duration of disease and ALFF values of the right inferior frontal gyrus and middle frontal gyrus were correlated with headache frequency and anxiety scores, respectively. Moreover, the abnormal dFC of the right LG with bilateral cuneus was positively correlated with anxiety scores. Conclusions: The dFC abnormalities of the visual cortex may be involved in pain integration with multinetworks and associated with anxiety disorder in episodic MwoA patients.

4.
Phys Chem Chem Phys ; 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35043813

RESUMO

The vibrationally resolved absorption spectra and ultrafast exciton dynamics in α-phase and ß-phase zinc phthalocyanine (ZnPc) aggregates are theoretically investigated using a non-Markovian stochastic Schrödinger equation combined with first-principles calculations. It is found that although similar double-peak structures arise in the Q-band region of the absorption spectra in both phases, these peaks are different in nature and exhibit distinct types of behavior with respect to the aggregation length. The analysis on the basis of an effective two-state model indicates that the two absorption peaks in the α phase are from mixing between the charge-transfer (CT) state and the bright Frenkel exciton (FE) state. By contrast, in the ß-phase, the low-energy peak is solely contributed by a low-lying bright FE state, whereas the high-energy peak originates from the interplay between the CT state and another high-lying bright FE state. For the relaxation processes right after photoexcitation from the Q-band region, it is found that within the first dozens of femtoseconds the ZnPc aggregates of both phases tend to temporarily fall into some intermediate states where the population distribution and average electronic energy do not obviously evolve. In addition, it is found that the optical transition of the low-lying bright FE state in the ß phase is not favorable for the formation of bound CT states due to the absence of enough driving forces.

5.
BMC Biol ; 20(1): 16, 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35022048

RESUMO

BACKGROUND: Many named species as defined in current bacterial taxonomy correspond to species complexes. Uncertainties regarding the organization of their genetic diversity challenge research efforts. We utilized the Agrobacterium tumefaciens species complex (a.k.a. Agrobacterium biovar 1), a taxon known for its phytopathogenicity and applications in transformation, as a study system and devised strategies for investigating genome diversity and evolution of species complexes. RESULTS: We utilized 35 genome assemblies, including 14 newly generated ones, to achieve a phylogenetically balanced sampling of A. tumefaciens. Our genomic analysis suggested that the 10 genomospecies described previously are distinct biological species and supported a quantitative guideline for species delineation. Furthermore, our inference of gene content and core-genome phylogeny allowed for investigations of genes critical in fitness and ecology. For the type VI secretion system (T6SS) involved in interbacterial competition and thought to be conserved, we detected multiple losses and one horizontal gene transfer. For the tumor-inducing plasmids (pTi) and pTi-encoded type IV secretion system (T4SS) that are essential for agrobacterial phytopathogenicity, we uncovered novel diversity and hypothesized their involvement in shaping this species complex. Intriguingly, for both T6SS and T4SS, genes encoding structural components are highly conserved, whereas extensive diversity exists for genes encoding effectors and other proteins. CONCLUSIONS: We demonstrate that the combination of a phylogeny-guided sampling scheme and an emphasis on high-quality assemblies provides a cost-effective approach for robust analysis in evolutionary genomics. We show that the T6SS VgrG proteins involved in specific effector binding and delivery can be classified into distinct types based on domain organization. The co-occurrence patterns of VgrG-associated domains and the neighboring genes that encode different chaperones/effectors can be used to infer possible interacting partners. Similarly, the associations between plant host preference and the pTi type among these strains can be used to infer phenotype-genotype correspondence. Our strategies for multi-level investigations at scales that range from whole genomes to intragenic domains and phylogenetic depths from between- to within-species are applicable to other bacteria. Furthermore, modularity observed in the molecular evolution of genes and domains is useful for inferring functional constraints and informing experimental works.

6.
Eur Radiol ; 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35037969

RESUMO

OBJECTIVES: To develop and externally validate a machine learning (ML) model based on diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) to identify the onset time of wake-up stroke from MRI. METHODS: DWI and FLAIR images of stroke patients within 24 h of clear symptom onset in our hospital (dataset 1, n = 410) and another hospital (dataset 2, n = 177) were included. Seven ML models based on dataset 1 were developed to estimate the stroke onset time for binary classification (≤ 4.5 h or > 4.5 h): Random Forest (RF), support vector machine with kernel (svmLinear) or radial basis function kernel (svmRadial), Bayesian (Bayes), K-nearest neighbor (KNN), adaptive boosting (AdaBoost), and neural network (NNET). ROC analysis and RSD were performed to evaluate the performance and stability of the ML models, respectively, and dataset 2 was externally validated to evaluate the model generalization ability using ROC analysis. RESULTS: svmRadial achieved the best performance with the highest AUC and accuracy (AUC: 0.896, accuracy: 0.878), and was the most stable (RSD% of AUC: 0.08, RSD% of accuracy: 0.06). The svmRadial model was then selected as the final model, and the AUC of the svmRadial model for predicting the onset time external validation was 0.895, with 0.825 accuracy. CONCLUSIONS: The svmRadial model using DWI + FLAIR is the most stable and generalizable for identifying the onset time of wake-up stroke patients within 4.5 h of symptom onset. KEY POINTS: • Machining learning model helps clinicians to identify wake-up stroke patients within 4.5 h of symptom onset. • A prospective study showed that svmRadial model based on DWI + FLAIR was the most stable in predicting the stroke onset time. • External validation showed that svmRadial model has good generalization ability in predicting the stroke onset time.

7.
Cell Death Discov ; 8(1): 15, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013140

RESUMO

Spinal cord injury (SCI) is a devastating traumatic condition. METTL14-mediated m6A modification is associated with SCI. This study was intended to investigate the functional mechanism of RNA methyltransferase METTL14 in spinal cord neuron apoptosis during SCI. The SCI rat model was established, followed by evaluation of pathological conditions, apoptosis, and viability of spinal cord neurons. The neuronal function of primary cultured spinal motoneurons of rats was assessed after hypoxia/reoxygenation treatment. Expressions of EEF1A2, Akt/mTOR pathway-related proteins, inflammatory cytokines, and apoptosis-related proteins were detected. EEF1A2 was weakly expressed and Akt/mTOR pathway was inhibited in SCI rat models. Hypoxia/Reoxygenation decreased the viability of spinal cord neurons, promoted LDH release and neuronal apoptosis. EEF1A2 overexpression promoted the viability of spinal cord neurons, inhibited neuronal apoptosis, and decreased inflammatory cytokine levels. Silencing METTL14 inhibited m6A modification of EEF1A2 and increased EEF1A2 expression while METTL14 overexpression showed reverse results. EEF1A2 overexpression promoted viability and inhibited apoptosis of spinal cord neurons and inflammation by activating the Akt/mTOR pathway. In conclusion, silencing METTL14 repressed apoptosis of spinal cord neurons and attenuated SCI by inhibiting m6A modification of EEF1A2 and activating the Akt/mTOR pathway.

9.
Inorg Chem ; 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35025491

RESUMO

Chemical modulation on the structures and physical properties of the coordination complexes is of great interest for the preparation of new functional materials. By changing the acidity or basicity of the reaction medium, the deprotonation degree of a multidentate ligand with multiple active protons, H4daps (H4daps = N',N'″-((1E,1'E)-pyridine-2,6-diylbis(ethan-1-yl-1-ylidene))bis(2-hydroxybenzohydrazide)), can be regulated on purpose. With this ligand of different deprotonation and charges, three new DyIII complexes ([Dy(H3daps)(CH3COO)2(EtOH)]·CH3COOH (1Dy), [Dy2(H2daps)2(EtOH)2(H2O)2(MeOH)2](CF3SO3)2·(H2O)2 (2Dy), and [Dy3(H1daps)2(H2daps)(µ3-OH)(EtOH)(H2O)] (3Dy)) of different nuclearities (mono-, di-, and trinuclear for 1Dy to 3Dy, respectively) have been synthesized and characterized structurally and magnetically. Analyses on the related bond lengths and resulting hydrogen bond modes in the complexes provide the details of the deprotonation position and the charge of the ligands, which can be in the form of H3daps-, H2daps2-, and H1daps3-. Interestingly, the more deprotonated ligand can act as a bridging ligand between the DyIII centers using the phenol and/or carbonyl oxygen atoms, which leads to the multinuclear structures. Magnetic studies on these complexes revealed that complex 1Dy is a field-induced single-molecule magnet (SMM), while complexes 2Dy and 3Dy show SMM behavior under a zero dc field.

10.
IEEE J Transl Eng Health Med ; 10: 2100208, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34984110

RESUMO

OBJECTIVE: Quantifying muscle tone is often based on a tester's subjective judgment in clinical settings. There is, however, a lack of suitable tools that can be used to objectively assess muscle tone. This study thus introduces a reliable, clinically-feasible device, called the Arm Circumference Motor Evaluation System (ACMES), for quantifying the muscle tone of upper limbs without using mechanical torque transducers. METHODS: While the ACMES conducts continuously passive arm circumduction motions, the voltage and current of the driving motor is transduced into torque values via a least square approximation. A torque sensor and springs with different spring constants were used for the validity and reliability test in the first part of this study. Fifteen healthy adults and two patients who had experienced a stroke participated in the second part, which was a clinical experiment used to examine the in-vivo test-retest reliability and to explore the inspection differences between healthy and patient participants. RESULTS: The results showed that the ACMES has high validity (R2: ~0.99) and reliability (R2: 0.96~0.99). The reliability of the ACMES used on human subjects was acceptable (R2: 0.83~0.85). The various muscle tone patterns could be found among healthy and stroke subjects via the ACMES. CONCLUSION: Clinically, abnormal muscle tone, which seriously affects motion performance, will be found in many diagnoses, such as stroke or cerebral palsy. However, objectively and feasibly measuring abnormal tone in modern clinical settings is still a challenging task. Thus, the ACMES was developed and tested to verify its feasibility as a measurement system for detecting the mechanical torque associated with muscle tone.

11.
FASEB J ; 36(2): e22144, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34990050

RESUMO

Renal fibrosis is a progressive, fatal renal disease characterized by the aberrant accumulation of myofibroblasts that produce excess extracellular matrix (ECM) in the renal interstitium and glomeruli. Yes-associated protein (YAP) has been regarded as a crucial modulator in myofibroblast transformation, but its upstream regulator remains a mystery. In the present study investigating the participation of m6A methylation during renal fibrosis through bioinformatics analysis, we identified YTHDF1, a modulator of m6A methylation, as a key contributor for renal fibrosis because it was highly expressed in human fibrotic kidneys and had a significant correction with YAP. Their co-localization in human fibrotic kidneys was additionally shown by immunofluorescence. We then found that YTHDF1 was also up-regulated in fibrotic mouse kidneys induced by unilateral ureteral obstruction (UUO), high-dose folic acid administration, or the unilateral ischemia-reperfusion injury, further supporting a causal role of YTHDF1 during renal fibrosis. Consistent with this notion, YTHDF1 knockdown alleviated the progression of renal fibrosis both in cultured cells induced by transforming growth factor-beta administration and in the UUO mouse model. Meanwhile, YAP was accordingly down-regulated when YTHDF1 was inhibited. Furthermore, the specific binding of YTHDF1 to YAP mRNA was detected using RNA Binding Protein Immunoprecipitation, and the up-regulation of fibrotic related molecules in cultured cells induced by YTHDF1 over-expression plasmid was attenuated by YAP siRNA. Taken together, our data highlight the potential utility of YTHDF1 as an indicator for renal fibrosis and suggest that YTHDF1 inhibition might be a promising therapeutic strategy to alleviate renal fibrosis via downregulating YAP.

12.
FASEB J ; 36(1): e22122, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34958158

RESUMO

Lysine-specific histone demethylase 1 (LSD1) as the first identified histone/lysine demethylase regulates gene expression and protein functions in diverse diseases. In this study, we show that the expression of LSD1 is increased in mouse kidneys with unilateral ureteral obstruction (UUO) and in cultured NRK-52E cells undergoing TGF-ß1-induced epithelial-mesenchymal transition (EMT). Inhibition of LSD1 with its specific inhibitor ORY1001 attenuated renal EMT and fibrosis, which was associated with decreased the deposition of extracellular matrix proteins and the expression of fibrotic markers, including α-smooth muscle actin (α-SMA) and fibronectin, and the recovery of E-cadherin expression and decrease of N-cadherin expression in UUO kidneys and in NRK-52E cells induced with TGF-ß1. Targeting LSD1 also decreased the expression of Snail family transcriptional repressor 1 (Snail-1) and its interaction with LSD1 in UUO kidneys and in NRK-52E cells treated with TGF-ß1. In addition, we identified a novel LSD1-14-3-3ζ-PKCα axis in the regulation of the activation of AKT and Stat3 and then the activation of fibroblasts. This study suggests that LSD1 plays a critical role in regulation of renal EMT and fibrosis through activation of diverse signaling pathways and places an emphasis that LSD1 has potential as a therapeutic target for the treatment of renal fibrosis.


Assuntos
Sistemas de Liberação de Medicamentos , Inibidores Enzimáticos/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Histona Desmetilases , Rim/enzimologia , Animais , Linhagem Celular , Transição Epitelial-Mesenquimal/genética , Fibrose , Histona Desmetilases/antagonistas & inibidores , Histona Desmetilases/genética , Histona Desmetilases/metabolismo , Nefropatias/tratamento farmacológico , Nefropatias/enzimologia , Nefropatias/genética , Masculino , Camundongos , Ratos
13.
Neural Regen Res ; 17(1): 137-143, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34100449

RESUMO

The survival of microglia depends on the colony-stimulating factor-1 receptor (CSF1R) signaling pathway under physiological conditions. Ki20227 is a highly selective CSF1R inhibitor that has been shown to change the morphology of microglia. However, the effects of Ki20227 on the progression of ischemic stroke are unclear. In this study, male C57BL/6 mouse models of focal cerebral ischemic injury were established through the occlusion of the middle cerebral artery and then administered 3 mg/g Ki20227 for 3 successive days. The results revealed that the number of ionized calcium-binding adaptor molecule 1/bromodeoxyuridine double positive cells in the infarct tissue was reduced, the degree of edema was increased, neurological deficits were aggravated, infarct volume was increased, and the number of peri-infarct Nissl bodies was reduced. The number of terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells in the peri-infarct tissue was increased. The expression levels of Bax and Cleaved caspase-3 were up-regulated. Bcl-2 expression was downregulated. The expression levels of inflammatory factors and oxidative stress-associated factors were increased. These findings suggested that Ki20227 blocked microglial proliferation and aggravated the pathological progression of ischemia/reperfusion injury in a transient middle cerebral artery occlusion model. This study was approved by the Animal Ethics Committee of Lanzhou University Second Hospital (approval No. D2020-68) on March 6, 2020.

14.
Chemosphere ; 290: 133352, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34922962

RESUMO

Microplastics (MPs) have received much attention in recent years because of their continuous photoaging process in aquatic environments. However, little research has been conducted on the photochemistry of aged microplastics and the associated effects on coexisting pharmaceuticals. This study investigated the photodegradation of cimetidine via aged polystyrene microplastics (PS-MPs) with different aging times (0-7 d) under simulated sunlight irradiation (700 W/m2). PS-MPs with 5 d of aging time resulted in much faster cimetidine degradation (>99%) after 2 h of irradiation than pristine PS-MPs (<8%). The enhanced photodegradation of cimetidine by aged PS-MPs was related to the increase in chromophoric oxygenated groups (CO, C-O) followed by redshifted absorbance through the photoaging process, which induced the formation of the environmentally persistent free radicals (EPFRs) OH, 1O2 and 3PS*. However, only 1O2 and 3PS* contributed to enhanced cimetidine photodegradation, with 1O2 playing a more important role in our case. This work also demonstrated that other compounds that are susceptible to indirect photolysis, such as codeine and morphine, are likewise significantly degraded under irradiation in the presence of aged PS-MPs. Although previous studies have reported how MPs can increase the persistence of contaminants, this study demonstrates that MPs can serve as photosensitizers and alter the fate of coexisting pharmaceuticals in aquatic environments.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34666066

RESUMO

PURPOSE: The reorganization of the limbic regions extend to general cognitive network is believed to exist in the chronicity of tinnitus with particular 'hubs' contributing to a 'noise-cancellation' mechanism. To test this hypothesis, we investigated the topological brain network of tinnitus in different periods. METHODS: Resting-state functional magnetic resonance imaging were obtained from 32 patients with acute tinnitus, 41 patients with chronic tinnitus and 60 age- and gender- matched healthy controls (HC). The topological features of their brain networks were explored using graph theory analysis. RESULTS: Common small-world attributes were compared between the three groups, all showed a significantly increased values in Cp, Lp, λ (all p < 0.05). Significantly increased nodal centralities in the left superior frontal gyrus and the right precuneus, significantly decreased nodal centralities in the right inferior temporal gyrus were observed for acute tinnitus patients compared to HC. While for chronic tinnitus patients, there were significant increased nodal centralities in the left hippocampus, amygdala, and temporal pole, but decreased nodal centralities in the right inferior temporal gyrus. Additionally, significant higher nodal centralities were found in bilateral medial superior frontal gyrus for acute tinnitus patients compared to chronic tinnitus patients. Besides, alterations in rich-club organization were found in acute tinnitus patients and chronic tinnitus patients compared with HC, with increased functional connections among rich-club nodes and peripheral nodes in patients with tinnitus. CONCLUSIONS: Brain network topological properties altered across prefrontal-limbic-subcortical regions in tinnitus. The existed hubs in tinnitus might indicate an emotional and cognitive burden in 'noise-cancellation' mechanism.

16.
Environ Pollut ; 292(Pt A): 118359, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34648842

RESUMO

Rapid urbanization and the aggregation of human activities in cities have resulted in large amounts of anthropogenic heat (AH) emission, which affects urban climate. Quantifying and assessing the AH emission values accurately and analyzing their spatial distribution characteristics is important to understand the energy exchange processes of urban areas. In this study, the high spatial resolution anthropogenic heat flux (AHF) quantification and spatial distribution analysis were conducted using multi-source data in the Beijing-Tianjin-Hebei region (BTH region) of China. First, the AH emission in district and city level were estimated using inventory method based on energy consumption and socio-economic statistical data; Then, AHF spatial quantification models were constructed based on high spatial resolution nighttime light (NTL) data and Point of interests (POI) data, and 130 m × 130 m gridded AHF quantification result in BTH region was realized; Finally, the potential numerical and spatial distribution patterns of AHF were analyzed using various indicators including contribution rate and aggregation index. The results show that: (1) The parameterized index constructed based on NTL and POI data shows a strong correlation with AHF, with R2 ranging from 0.79 to 0.94 and a mean absolute error (MAE) value of 0.72 w·m-2, which can be applied to the quantification of gridded AHF values with high resolution. The highest total AHF in the study area is 214 w·m-2, and the average value is 2.24 w·m-2. (2) Considering the sources of AHF, industrial emission sources in BTH region contribute the most to the total AHF, but commercial building emission sources in Beijing have a higher contribution, which can reach 33.8%. (3) Different types of AHF have different spatial aggregation levels. Commercial building emission and human metabolic emission have the highest aggregation level, and transportation emission has the lowest aggregation level.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Pequim , China , Cidades , Monitoramento Ambiental , Temperatura Alta , Humanos , Material Particulado/análise
19.
J Diabetes Res ; 2021: 5171618, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34877358

RESUMO

Alterations of brain functional connectivity in patients with type 2 diabetes mellitus (T2DM) have been reported by resting-state functional magnetic resonance imaging studies, but the underlying precise neuropathological mechanism remains unclear. This study is aimed at investigating the implicit alterations of functional connections in T2DM by integrating functional connectivity strength (FCS) and Granger causality analysis (GCA) and further exploring their associations with clinical characteristics. Sixty T2DM patients and thirty-three sex-, age-, and education-matched healthy controls (HC) were recruited. Global FCS analysis of resting-state functional magnetic resonance imaging was performed to explore seed regions with significant differences between the two groups; then, GCA was applied to detect directional effective connectivity (EC) between the seeds and other brain regions. Correlations of EC with clinical variables were further explored in T2DM patients. Compared with HC, T2DM patients showed lower FCS in the bilateral fusiform gyrus, right superior frontal gyrus (SFG), and right postcentral gyrus, but higher FCS in the right supplementary motor area (SMA). Moreover, altered directional EC was found between the left fusiform gyrus and bilateral lingual gyrus and right medial frontal gyrus (MFG), as well as between the right SFG and bilateral frontal regions. In addition, triglyceride, insulin, and plasma glucose levels were correlated with the abnormal EC of the left fusiform, while disease duration and cognitive function were associated with the abnormal EC of the right SFG in T2DM patients. These results suggest that T2DM patients show aberrant brain function connectivity strength and effective connectivity which is associated with the diabetes-related metabolic characteristics, disease duration, and cognitive function, providing further insights into the complex neural basis of diabetes.

20.
J Cell Mol Med ; 2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34889045

RESUMO

Lipopolysaccharide (LPS)-induced sepsis-associated acute kidney injury (SA-AKI) is a model of clinical serious care syndrome, with high morbidity and mortality. Tacrolimus (TAC), a novel immunosuppressant that inhibits inflammatory response, plays a pivotal role in kidney diseases. In this study, LPS treated mice and cultured podocytes were used as the models of SA-AKI in vivo and in vitro, respectively. Medium- and high-dose TAC administration significantly attenuated renal function and renal pathological manifestations at 12, 24 and 48 h after LPS treatment in mice. Moreover, the Toll-like receptor 4 (TLR4)/myeloid differential protein-88 (MyD88)/nuclear factor-kappa (NF-κB) signalling pathway was also dramatically inhibited by medium- and high-dose TAC administration at 12, 24 and 48 h of LPS treatment mice. In addition, TAC reversed LPS-induced podocyte cytoskeletal injury and podocyte migratory capability. Our findings indicate that TAC has protective effects against LPS-induced AKI by inhibiting TLR4/MyD88/NF-κB signalling pathway and podocyte dysfunction, providing another potential therapeutic effects for the LPS-induced SA-AKI.

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