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1.
Front Pharmacol ; 15: 1360972, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38650625

RESUMO

Ethnopharmacological relevance: As a representative classical prescription, Sijunzi decoction has powerful therapeutic effects on spleen-stomach qi insufficiency. Ulcerative colitis (UC) is a chronic, diffuse, and non-specifically inflammatory disorder, the etiology of which still remains unclear. In the traditional Chinese medicine (TCM) perspective, splenic asthenia is the primary cause of UC. Based on this, Sijunzi decoction has been extensively used in TCM clinical practice to alleviate UC in recent years. However, the pharmacological mechanism of Sijunzi decoction in modern medicine is still not completely clear, which limits its clinical application. Aim of the study: The purpose of this study was to investigate the Sijunzi decoction's curative effect on acute UC mice and probe into its potential pharmacological mechanism. Materials and methods: The UC mouse model was set up by freely ingesting a 3% dextran sulfate sodium (DSS) solution. The relieving role of Sijunzi decoction on UC in mice was analyzed by evaluating the changes in clinical parameters, colon morphology, histopathology, inflammatory factor content, intestinal epithelial barrier protein expression level, and gut microbiota balance state. Finally, multivariate statistical analysis was conducted to elucidate the relationship between inflammatory factors, intestinal epithelial barrier proteins, and gut microbiota. Results: First, the research findings revealed that Sijunzi decoction could visibly ease the clinical manifestation of UC, lower the DAI score, and attenuate colonic damage. Moreover, Sijunzi decoction could also significantly inhibit IL-6, IL-1ß, and TNF-α while increasing occludin and ZO-1 expression levels. Subsequently, further studies showed that Sijunzi decoction could remodel gut microbiota homeostasis. Sijunzi decoction was beneficial in regulating the levels of Alistipes, Akkermansia, Lachnospiraceae_NK4A136_group, and other bacteria. Finally, multivariate statistical analysis demonstrated that key gut microbes were closely associated with inflammatory factors and intestinal epithelial barrier proteins. Conclusion: Sijunzi decoction can significantly prevent and treat UC. Its mechanism is strongly associated with the improvement of inflammation and intestinal epithelial barrier damage by regulating the gut microbiota.

2.
Front Endocrinol (Lausanne) ; 15: 1354577, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38577568

RESUMO

Introduction: Osteoporosis, a disease of reduced bone mass and microstructural deterioration leading to fragility fractures, is becoming more prevalent as aging progresses, significantly increasing the socioeconomic burden. In past studies, there has been a growing awareness of the harmful effects of heavy metals on bone, with cadmium being a significant exposure factor. The purpose of this study was to look into the association between adult bone mineral density(BMD) and blood cadmium levels. Methods: Based on information from the 2013-2014, 2017-2018 NHANES, weighted multiple regression, generalized weighted modeling, and smoothed curve fitting were utilized to investigate the association between blood cadmium and femur BMD. Furthermore, subgroup analyses were conducted to investigate any differences in the associations between age, sex, race, chronic kidney disease, and diabetes. Results: In 2,146 participants, blood cadmium levels and total femur [-0.02 (-0.03, -0.01), 0.0027], femoral neck [-0.01 (-0.02, -0.00), 0.0240], femoral trochanter [-0.01 (-0.02, -0.00), 0.0042], and intertrochanteric femoral trochanter [-0.02 (-0.03, -0.00), 0.0101] BMD were negatively correlated. Subgroup analyses showed that this association was more pronounced in women, non-Hispanic white people and other Hispanics, and those with chronic kidney disease and diabetes. Our results pointed to a negative relationship between femoral BMD and blood cadmium. This negative association varied by age, sex, race, diabetes, and chronic kidney disease. In particular, bone mineral density was more significantly negatively affected by blood cadmium levels in groups with diabetes and chronic kidney disease. Conclusion: Our findings demonstrated a significant negative association between blood cadmium levels and bone mineral density in a population of U.S. adults.


Assuntos
Diabetes Mellitus , Insuficiência Renal Crônica , Adulto , Humanos , Feminino , Densidade Óssea , Estudos Transversais , Cádmio , Inquéritos Nutricionais
3.
Front Nutr ; 11: 1335074, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38298424

RESUMO

Background: A link between food-induced inflammation and common chronic diseases has been identified in studies. However, there was uncertainty about the influence of dietary inflammatory potential on the risk of chronic kidney disease (CKD) among middle-aged and older groups. Our research aimed to examine the connection between dietary inflammatory index (DII) to CKD in people aged 40 years and older. Methods: This study comprised ten cycles of the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Linear associations of DII with CKD, low-eGFR, and albuminuria were examined using multiple logistic regression, whereas non-linear associations were assessed by smoothed curve fitting. Besides, we conducted subgroup analyses and interaction tests. Results: Of the 23,175 middle-aged and older individuals, a total of 5,847 suffered from CKD, making up 25.23% of all participants. After adjustment for all covariates, we found that increased DII scores were positive with an increased hazard of CKD (OR = 1.08, 95% CI: 1.05, 1.10, p < 0.0001), and the same was shown between DII and low-eGFR (OR = 1.16, 95% CI: 1.13, 1.19, p < 0.0001). After further converting DII into categorical variables, the above relationship still existed. These relations were consistent in different ages, genders, BMI, whether smoking, whether suffering from hypertension, and whether suffering from diabetes, with no significant stratification differences (all P for interaction >0.05). Surprisingly, we did not find a statistically significant correlation of DII to albuminuria after complete adjustment for covariates (OR = 1.02, 95% CI: 1.00, 1.05, p = 0.0742). Even when DII was considered as a categorical variable, this relation was still not statistically significant. Furthermore, we found an association in the shape of a U between DII and low-eGFR in the fully adjusted model, with a turning point at a DII of 1.6. Conclusion: Our findings indicated that middle-aged and older persons with greater levels of DII had a significantly higher risk of CKD.

4.
Opt Express ; 32(3): 3779-3792, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38297591

RESUMO

In this study, absolute tests of three flats were performed by using an 800 mm Fizeau interferometer. The flats were installed by employing double-wedge rubber, and the deformation of the flats, primarily involving power and spherical aberrations, was analyzed by conducting finite element analysis. The measurement results revealed an astigmatism component that did not follow the rotation. The astigmatism was separated from the measurement result, and the remaining aberration was consistent with the simulation results, confirming that the astigmatism deformation did not originate from the rubber installation. Subsequently, an absolute test of an 800 mm flat was completed, and the results were compared with those of the traditional three-flat absolute test and Zygo interferometer. The directions of the vertical diameter lines were consistent. The peak-to-valley difference in the full-surface shape was less than 4 nm, and the root mean square was less than 1 nm. The surface errors of flats A and C were consistent with the result of replacing the reference flat, B, with the fourth flat, D, to perform an absolute test. The difference between flats A and C was similar to Zygo's results, thus eliminating the influence of the transmission flat. These results verified the accuracy of the results.

5.
STAR Protoc ; 5(1): 102881, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38386546

RESUMO

Here, we present a protocol for inducing fibrosis in human kidney-2 (HK2) cells followed by quantitative real-time PCR analysis of fibrosis-related genes. We describe steps for growing and expanding cells, inducing HK2 fibrosis, and collecting cells for downstream applications. Given the limited cell quantity in culture flasks and the challenges of cell collection, we utilized 10-cm Petri dishes for cell harvesting, with each experimental group comprising five replicate samples. For complete details on the use and execution of this protocol, please refer to Zhang et al.1.


Assuntos
Células Epiteliais , Rim , Humanos , Reação em Cadeia da Polimerase em Tempo Real , Fibrose
6.
Front Endocrinol (Lausanne) ; 14: 1281396, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38075068

RESUMO

Introduction: According to reports, obesity has a significant impact on bone health. And the weight-adjusted-waist index (WWI), superior to BMI and waist circumference (WC), is a new obesity indicator arising in recent years. This research investigated the relationship between WWI and total bone mineral density (BMD) for adults aged 20 to 59. Methods: Using data from the 2011-2018 NHANES, we looked into the independent link between WWI and total BMD as well as its nonlinearity using weighted multiple linear regression and smooth curve fitting. Two-stage linear regression models were employed to calculate the threshold effects. There were additional subgroup analyses and testing for interactions. Results: Multiple linear regression studies on a total of 10,372 individuals showed a significant inverse link between WWI and total BMD in adults between 20 and 59 [ß = -0.04, 95% CI: (-0.04, -0.03), P<0.0001]. And smoking, race, and chronic kidney disease (CKD) had no significant effect on this negative connection (P for interaction >0.05). In addition, we found a nonlinear relationship between WWI and total BMD in diabetic and CKD patients, for which the saturation point was 11.38 cm/√kg in the CKD patient group and 10.29 cm/√kg in the diabetic patient group. Conclusion: Our analysis demonstrated a significant inverse association between WWI and total BMD in adults aged 20-59.


Assuntos
Densidade Óssea , Diabetes Mellitus , Insuficiência Renal Crônica , Adulto , Humanos , Índice de Massa Corporal , Inquéritos Nutricionais , Obesidade
7.
Aging (Albany NY) ; 15(22): 13345-13367, 2023 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-38019470

RESUMO

BACKGROUND: Neuroblastoma (NB) is a childhood cancer originating from immature nerve cells in the sympathetic nervous system. Current clinical and molecular subtyping methods for NB have limitations in providing accurate prognostic information and guiding treatment decisions. RESULTS: To overcome these challenges, we explored the microenvironment of NB based on the knowledge-based functional gene expression signatures (Fges), which revealed heterogeneous subtypes. Consensus clustering of Fges activity scores identified three subtypes (Cluster 1, Cluster 2, and Cluster 3) that demonstrated significant differences in prognosis compared to mainstream subtypes. We assessed the immune infiltration, immunogenicity, CD8T cytotoxicity, and tumor purity of these subtypes, uncovering their distinct biological functions. Cluster 1 and Cluster 2 exhibited higher immunoreactivity, while Cluster 3 displayed higher tumor purity and poor prognosis. Gene ontology annotation and pathway analysis identified immune activation in Cluster 1, epithelial-mesenchymal transition (EMT) in Cluster 2, and cell cycle processes in Cluster 3. Notably, the impact of EMT activity on prognosis may vary across NB subtypes. A classification model using XGBoost accurately predicted subtypes in independent NB cohorts, with significant prognostic differences. GPR125, CDK4, and GREB1 emerged as potential therapeutic targets in Cluster 3. CD4K inhibitors showed subtype-specific responses, suggesting tailored treatment strategies. Single-cell analysis highlighted unfavorable clinical features in Cluster 3, including high-risk classification and reduced cytotoxicity. Suppressed interactions between monocytes, macrophages, and regulatory T cells were observed, affecting immune regulation and patient prognosis. CONCLUSION: To summarize, we have identified a new independent prognostic factor in NB that underscores the significant correlation between tumor phenotype and immune contexture. These findings deepen our understanding of NB subtypes and immune cell interactions, paving the way for more effective treatment approaches.


Assuntos
Neuroblastoma , Humanos , Criança , Prognóstico , Neuroblastoma/metabolismo , Resultado do Tratamento , Transição Epitelial-Mesenquimal , Transcriptoma , Microambiente Tumoral/genética
8.
Front Bioeng Biotechnol ; 11: 1249706, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37915548

RESUMO

At present, the clinical treatment of osteomyelitis and osteomyelitis-induced bone defects is challenging, easy to recur, drug toxic side effects, secondary or multiple surgeries, etc. The design of biodegradable composite biomaterials to improve antibiotics in the local precise anti-infection at the same time to complete the repair of bone defects is the current research hot spot. Herein, a composite hydrogel with a double bond at the end (FA-MA) was prepared by affinity addition reaction between fish collagen (FA) and methacrylic anhydride (MA) under photoinitiator initiation conditions, then, FA-MA was amino-activated by EDC/NHC, and vancomycin was attached to FA-MA via amide bonding to prepare FA-MA-Van hydrogels, and finally, the composite hydrogel microspheres were prepared by microfluidic technology. The structure of the hydrogel was confirmed by SEM (elemental analysis), optical microscopy, FTIR, and XPS to confirm the successful preparation. The composite hydrogel microspheres showed the better antimicrobial effect of hydrogel microspheres by bacterial coated plate experiments and SEM morphology results, with the antimicrobial class reaching 99.8%. The results of immunofluorescence staining and X-ray experiments showed that the hydrogel microspheres had a better effect on promoting bone repair. This engineered design of hydrogel microspheres provides clinical significance for treating osteomyelitis at a later stage.

9.
iScience ; 26(11): 107332, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37927553

RESUMO

Chronic kidney disease (CKD) is a common disease that seriously endangers human health. However, the potential relationship between xanthine oxidoreductase (XOR) activity and CKD remains unclear. In this study, we used clinical data, CKD datasets from the Gene Expression Omnibus database, and untargeted metabolomics to explain the relationship between XOR activity and CKD. First, XOR activity showed high correlation with the biomarkers of CKD, such as serum creatinine, blood urea nitrogen, uric acid, and estimated glomerular filtration rate. Then, we used least absolute shrinkage and selection operator logical regression algorithm and random forest algorithm to screen CKD molecular markers from differentially expressed genes, and the results of qRT-PCR of XDH, KOX-1, and ROMO1 were in accordance with the results of bioinformatics analyses. In addition, untargeted metabolomics analysis revealed that the purine metabolism pathway was significantly enriched in CKD patients in the simulated models of kidney fibrosis.

10.
Front Psychol ; 14: 1218534, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37519352

RESUMO

Introduction: Given the importance of parent involvement to students' academic achievement, researchers have used a variety of methods to investigate the relationship between the two, but few focus on the relationship between parental homework involvement and students' achievement in a specific subject by using meta-analysis. This meta-analysis investigated the relationship between parent homework involvement and students' mathematics achievement from two dimensions: supportive (SPI) and intrusive parent homework involvement (IPI), along with their moderators. Methods: Accessed through Web of Science, Taylor and Francis Online, EBSCO, Springer Link, Elsevier, and ProQuest databases, a total of 20 empirical studies between 2005 to 2022, 41 independent effect sizes were included (N = 16,338). Effect size estimations were obtained by transforming Fisher's correlation coefficient. This study has conducted the heterogeneity tests of the magnitudes grouped according to different moderators, and investigated the publication bias that affects meta-analysis studies. Results and discussion: The results showed an overall positive link between SPI and students' mathematics achievement (r = 0.076, 95% CI = [0.037, 0.114]) and a negative link between IPI and students' mathematics achievement (r = -0.153, 95% CI = [-0.226, -0.079]). For the link of SPI and students' mathematics achievement, the effect sizes were (a) strongest when SPI was measured by autonomy support, followed by content support and provision of structure respectively; (b) stronger when students' mathematics achievement indicated by non-standardized measurement than standardized measurement. For the link of IPI and students' mathematics achievement, the effect sizes varied across grade level, strongest in high school, followed by middle school and lowest in primary school. These findings provide important implications for how to improve parental homework involvement practice to increase students' mathematics achievement.

11.
J Cell Mol Med ; 27(19): 2876-2889, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37471571

RESUMO

Acute kidney injury (AKI), mainly caused by Ischemia/reperfusion injury (IRI), is a common and severe life-threatening disease with high mortality. Accumulating evidence suggested a direct relationship between endoplasmic reticulum (ER) stress response and AKI progression. However, the role of the transmissible ER stress response, a new modulator of cell-to-cell communication, in influencing intercellular communication between renal tubular epithelial cells (TECs) and macrophages in the AKI microenvironment remains to be determined. To address this issue, we first demonstrate that TECs undergoing ER stress are able to transmit ER stress to macrophages via exosomes, promoting macrophage polarization towards the pro-inflammatory M1 phenotype in vitro and in vivo. Besides, the miR-106b-5p/ATL3 signalling axis plays a pivotal role in the transmission of ER stress in the intercellular crosstalk between TECs and macrophages. We observed an apparent increase in the expression of miR-106b-5p in ER-stressed TECs. Furthermore, we confirmed that ALT3 is a potential target protein of miR-106b-5p. Notably, the inhibition of miR-106b-5p expression in macrophages not only restores ATL3 protein level but also decreases transmissible ER stress and hinders M1 polarization, thus alleviating AKI progression. Additionally, our results suggest that the level of exosomal miR-106b-5p in urine is closely correlated with the severity of AKI patients. Taken together, our study sheds new light on the crucial role of transmissible ER stress in the treatment of AKI through the regulation of the miR-106b-5p/ATL3 axis, offering new ideas for treating AKI.

12.
Open Med (Wars) ; 18(1): 20230736, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37305520

RESUMO

To explore the pharmacological mechanism of naringin (NRG) in renal fibrosis (RF) based on network pharmacology combined with molecular docking and experimental validation. We used databases to screen for the targets of NRG and RF. The "drug-disease network" was established using Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of targets were performed using Metascape, and molecular docking was performed using Schrödinger. We established an RF model in both mice and cells to validate the results of network pharmacology. After screening the database, we identified 222 common targets of NRG and RF and established a target network. Molecular docking showed that the target AKT had a good interaction with NRG. We found that the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway was enriched by multiple targets and served as a target for experimental validation through GO and KEGG. The results revealed that NRG ameliorated renal dysfunction, reduced the release of inflammatory cytokines, decreased the expression of α-SMA, collagen I, and Fn, and recovered the expression of E-cad by inhibiting the PI3K/AKT signaling pathway. Our study used pharmacological analysis to predict the targets and mechanisms of NRG against RF. Furthermore, experiments proved that NRG inhibited RF effectively by targeting the PI3K/AKT signaling pathway.

13.
Opt Express ; 31(13): 21239-21252, 2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37381228

RESUMO

This study proposed a non-iterative phase tilt interferometry (NIPTI) for the tilt shift calculation and phase extraction, which can solve the random tilt-shift problem caused by external vibration. The method approximates the higher order terms of the phase to make it suitable for linear fitting. Then according to an estimated tilt, the accurate tilt shift can be obtained by least squares method without iteration, and the phase distribution can be calculated by it. The simulation results indicated that the root mean square error of the phase calculated by the NIPTI can reach up to 0.0002λ. The experimental results showed that the calculated phase exhibited no significant ripple when using the NIPTI for cavity measurements in a time-domain phase shift Fizeau interferometer. Moreover, the root mean square repeatability of the calculated phase reached up to 0.0006λ. It indicates that the NIPTI provides an efficient and high-precision solution for random tilt-shift interferometry under vibration.

14.
Metabolites ; 13(5)2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37233705

RESUMO

Plant growth-promoting rhizobacteria (PGPR) can colonize plant root surfaces or form biofilms to promote plant growth and enhance plant resistance to harsh external environments. However, plant-PGPR interactions, especially chemical signaling molecules, are poorly understood. This study aimed to gain an in-depth understanding of the rhizosphere interaction mechanisms between PGPR and tomato plants. This study found that inoculation with a certain concentration of Pseudomonas stutzeri significantly promoted tomato growth and induced significant changes in tomato root exudates. Furthermore, the root exudates significantly induced NRCB010 growth, swarming motility, and biofilm formation. In addition, the composition of the root exudates was analyzed, and four metabolites (methyl hexadecanoate, methyl stearate, 2,4-di-tert-butylphenol, and n-hexadecanoic acid) significantly related to the chemotaxis and biofilm formation of NRCB010 were screened. Further assessment showed that these metabolites positively affected the growth, swarming motility, chemotaxis, or biofilm formation of strain NRCB010. Among these, n-hexadecanoic acid induced the most remarkable growth, chemotactic response, biofilm formation, and rhizosphere colonization. This study will help develop effective PGPR-based bioformulations to improve PGPR colonization and crop yields.

15.
BMC Nephrol ; 24(1): 38, 2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36797683

RESUMO

BACKGROUND: The role of Klotho as a multifunctional protein in anemia is unclear. This study aimed to determine the association between anemia and serum Klotho concentrations in middle-aged and elderly populations. METHODS: In this cross-sectional study, we used data collected from the National Health and Nutrition Examination Survey (NHANES) 2007-2016. A total of 13,357 individuals who received serum Klotho measurements, biochemical tests, and demographic surveys were analyzed. Multivariate linear regression models adjusting for covariates were used to investigate the associations between anemia and serum Klotho. RESULTS: Multivariable regression showed that serum Klotho correlates positively with hemoglobin and red blood cells and inversely with red cell distribution width. After adjusting for all covariates, compared with Q4, there was a significantly increased risk of anemia in serum Klotho quartiles 1 to 2 (OR=1.54, 95% CI:1.21-1.95, P=0.002; OR=1.30, 95% CI:1.02-1.64, P=0.042,respectively). Segmented regression showed that for every 100 pg/mL increase in serum Klotho <9.746 pg/mL, the risk of anemia was reduced by 10.9%, and this reduction was significant (P<0.001). Furthermore, stratified analyses yielded a stronger association between reduced anemia and high levels of Klotho in men and those with diabetes (P< 0.05 for interaction). However, this association was not found to be significantly altered by chronic kidney disease. CONCLUSIONS: In summary, we indicated that low serum Klotho is associated with an increased likelihood of anemia using a nationally representative sample of middle-aged and older adults.


Assuntos
Anemia , Proteínas Klotho , Insuficiência Renal Crônica , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Transversais , Hemoglobinas/análise , Inquéritos Nutricionais , Proteínas Klotho/sangue
16.
Appl Opt ; 62(3): 745-755, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36821280

RESUMO

In this paper, a simultaneous phase-shifting point-diffraction interferometer (SPS-PDI)  at 632.8 nm is designed with the assistance of an off-axis parabolic mirror (OAPM), through which the dynamic wavefront with 400 mm aperture can be detected. In the system, a polarization point-diffraction plate (P-PDP) is developed to modulate the polarization states of the reference light and the test light through a simultaneous phase-shifting system based on a chessboard phase grating and a retarder array, and four phase-shifting interferograms can be acquired to realize dynamic detection. Furthermore, the circular carrier squeezing interferometry (CCSI) is proposed to suppress the phase errors generated by position mismatch, intensity distortion, and phase-shift error. The detection result of the SPS-PDI is consistent with the 4D PhaseCam6000 dynamic interferometer. The difference of the peak-to-valley (PV) and root-mean-square (RMS) values are only 0.04λ and 0.008λ. Additionally, the capacity to detect dynamic wavefront is good.

17.
Opt Express ; 30(21): 37619-37636, 2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-36258347

RESUMO

In interferometer measurements, the inconsistency of the optical range through which the reference and test lights pass introduces a retrace error in the phase measurement. In this study, we propose an iterative retrace error correction method in interferometry. A black-box model is established based on the linear and squared relationships between the retrace error and the tilt of the testing surface. The error correction phase is obtained using the least-squares method; thereafter, the global tilt is determined to iteratively correct the retrace error. The root mean square (RMS) of the residuals was > 3.2 × 10-5λ, >6.4 × 10-3λ, and >1.4 × 10-3λ in the simulation, experimentally computed retrace error correction in the planar measurement, and spherical measurement, respectively, proving that the retrace error can be effectively corrected.

18.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 39(9): 983-987, 2022 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-36082570

RESUMO

OBJECTIVE: To explore the clinical and genetic characteristics of a Chinese pedigree affected by glycogen storage disease (GSD) type Ia with gout as the first manifestation. METHODS: Clinical and biochemical data of the pedigree were collected. Available members of the pedigree were subjected to gene sequencing, and the result was analyzed by bioinformatics software. The pedigree was followed up for five years. RESULTS: The proband was a young female manifesting recurrent gout flare, hypoglycemia, and hypertriglyceridemia. One of her younger brothers also presented with dysplasia and hepatic adenoma. Gene sequencing revealed that the proband and her younger brother both harbored c.1022T>A (p.I1e341Asn) and c.230+5G>A compound heterozygous variants of the G6PC gene , which were inherited from their father and mother, respectively. Among these, the c.230+5G>A is an intron region variant which was unreported previously, and bioinformatics analysis showed that it may impact mRNA splicing of the gene. The proband was treated with raw corn starch, allopurinol, and fenofibrate. Gout was well controlled, and she had given birth to a baby girl without GSD. CONCLUSION: GSD Ia should be considered among young gout patients with hypoglycemia and hepatomegaly, for which gene sequencing is warranted. GSD Ia has a good prognosis after comprehensive treatment with diet and medicine.


Assuntos
Gota , Hipoglicemia , China , Feminino , Doença de Depósito de Glicogênio Tipo I , Gota/genética , Humanos , Masculino , Linhagem , Exacerbação dos Sintomas
19.
Biomaterials ; 289: 121779, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36099712

RESUMO

Due to the aggregation-caused quenching (ACQ) and weak photo-penetrating ability, the application of phototheranostic agents in drug delivery field is greatly limited. Ferroptosis, a newly discovered cell death mode, has not been extensively studied in the field of phototherapy up to now. Here, a new near-infrared II (NIR-II) molecule with aggregation-induced emission (AIE) property (named TSST) co-assembled with DHA-PEG and ferrocene as nanoparticles (DFT-NP), which was rationally designed and synthesized. The DFT-NP exhibited enhanced NIR-II fluorescence, photothermal, photoacoustic, magnetic resonance imaging, AIE and ferroptosis capacities. The NIR-II fluorescence intensity of obtained nanoparticles was improved, owing to the strong interaction between DHA and TSST, which limited the intramolecular rotation restriction and non-radiative attenuation of TSST to discourage energy dissipation in aggregation state. Inspiringly, the generated photothermal effect by DFT-NP can promote the Fenton reaction of ferrocene and H2O2, resulting in dissolution of the nanoparticles and cancer cells expedited ferroptosis via accumulation lipid free radicals of DHA. The released TSST enhanced the photothermal and photoacoustic imaging effects through removing the DHA restriction to restore the non-radiative attenuation. This work is the first example of nanoparticles that integrates four-mode imaging, photothermal and ferroptosis-induced therapy functions, which offers great advantages for potential clinical applications.


Assuntos
Ferroptose , Nanopartículas , Neoplasias , Técnicas Fotoacústicas , Linhagem Celular Tumoral , Compostos Ferrosos , Humanos , Peróxido de Hidrogênio , Metalocenos , Neoplasias/terapia , Imagem Óptica/métodos , Técnicas Fotoacústicas/métodos , Fototerapia/métodos , Terapia Fototérmica , Nanomedicina Teranóstica/métodos
20.
Ren Fail ; 44(1): 1376-1387, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35969012

RESUMO

Renal ischemia-reperfusion injury (IRI) is a common prerequisite of acute renal injury (AKI) that involves the entire system and induces critical illness. The C domain of insulin-like growth factor-1 (IGF-1C) plays an important role in promoting angiogenesis and enhancing the inflammatory response. However, given the shortcomings of its short half-life and poor stability, the application of IGF-1C is restricted. In the present study, IGF-1C nanoparticles (NP-IGF-1C) were constructed by combining 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide (polye thyleneglycol)](DSPE-PEG-MAL) and IGF-1C through a Michael addition reaction to evaluate the effects of NP-IGF-1C on preventing IRI. In vitro studies have shown that NP-IGF-1C is not cytotoxic and protects cells from oxidative damage. The renal enrichment and biocompatibility of NP-IGF-1C were determined in vivo by connecting fluorescent molecules to NP-IGF-1C for in vivo imaging and pathological staining of important organs. After IRI, renal function decreased, and inflammatory cell infiltration, oxidative stress and apoptosis increased. As expected, NP-IGF-1C reversed these changes, indicating that NP-IGF-1C played a protective role in the process of IRI, which may be mediated by its antioxidant, anti-inflammatory and antiapoptotic activities.


Assuntos
Injúria Renal Aguda , Nanopartículas , Traumatismo por Reperfusão , Injúria Renal Aguda/patologia , Animais , Rim , Camundongos , Estresse Oxidativo , Traumatismo por Reperfusão/metabolismo
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