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1.
Food Chem ; 367: 130658, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34343808

RESUMO

Camel milk is rich in nutrients and its impact on human medicine and nutrition cannot be ignored. We conducted an in-depth analysis of milk proteins obtained from two camel breed (Camelus bactrianus, CB and Camelus dromedarius, CD). Label-free proteomic technology was performed to analysis the MFGM and whey proteomes of CB and CD milk. In total, 1133 MFGM proteins and 627 whey proteins were identified from camel milk. Results revealed that 216 MFGM proteins and 109 whey proteins were significantly different between them. In addition, the cellular process, cell and binding were the predominately GO annotations of milk proteins. KEGG analysis shown that most proteins were involved in metabolic pathways. Furthermore, many proteins were found to be involved in PI3K/AKT signaling pathway, which could be the possible reason for hypoglycemic effect of camel milk. These results could provide a further understanding for unique biological characteristics of camel milk proteins.


Assuntos
Camelus , Proteoma , Animais , Glicolipídeos , Glicoproteínas , Gotículas Lipídicas , Proteínas do Leite , Fosfatidilinositol 3-Quinases , Proteômica , Soro do Leite , Proteínas do Soro do Leite
2.
Front Immunol ; 12: 731774, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594337

RESUMO

The programmed cell death protein 1 inhibitor pembrolizumab, an immune checkpoint inhibitor, has subsequently been approved for the treatment of a wide variety of malignant tumors. Compared with conventional chemotherapy, immunotherapy is associated with a unique set of immune reactions, known collectively as immune-related adverse events. Although often mild, dermatologic toxicity can occasionally be high grade and potentially life-threatening. Here we describe a rare case of bullous pemphigoid (BP) associated with pembrolizumab. A 79-year-old male patient presented with scattered erythema, papules, blisters, and pruritus after pembrolizumab treatment. Then, the rash gradually aggravated and spread to the whole body. The extensive edematous erythema, blisters, bullae, and blood blisters were loose and easy to rupture, forming an erosive surface and with pruritus and obvious pain. The hemidesmosomal protein BP180 (type XVII collagen) was detectable in the serum, and the histological examination diagnosis was bullous pemphigoid. After 10 days of glucocorticoid (methylprednisolone, iv, 80 mg/day) treatment, new blister formation ceased. We need to increase the awareness on and facilitate the earlier identification of the cutaneous adverse effects of BP with immunotherapy so that treat can begin early in order to limit the duration and severity of toxicity.

3.
J Chem Theory Comput ; 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34605634

RESUMO

A novel adiabatic-to-diabatic (ATD) transformation strategy, namely, the extended Mulliken-Hush (XMH) method, is proposed to evaluate diabatic properties including electronic couplings, potential energy surfaces, and their crossings. The XMH method is developed by adopting our recently proposed ATD transformation formula of a general vectorial physical observable, in which a useful ATD transformation is further determined by using an auxiliary dipole between localized frontier orbitals as a simple approximation of the diabatic transition dipole. The XMH method is simple and practical that provides a flexible way to construct diabatic states. To some extent, it can be regarded as an extension of the generalized Mulliken-Hush (GMH) method since the latter takes a stronger approximation, in which the diabatic transition dipole is assumed to be vanishing. Test calculations on the HeH2+ system show that the electronic couplings predicted by the XMH method are closer to the ones calculated by the valence bond block-diagonalization approach than the GMH ones since the XMH method takes into account both the magnitude and direction of the diabatic transition dipole, which is consistent with the properties of this molecule. In the study of electron transfer in the two kinds of donor-bridge-acceptor systems, the XMH method maintains the simplicity of the GMH method and gives reasonable results even when the latter fails, wherein the diabatic transition dipole is nearly perpendicular to the difference of the initial and final adiabatic dipoles. More importantly, the XMH method can be easily combined with high-level electronic structure methods, in which the properties of the ground and excited states may be more accurately calculated, and hence, one may expect that further development of the XMH method would result in a general computational model for studying electron transfer reactions.

4.
J Neuroinflammation ; 18(1): 226, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645465

RESUMO

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is a severe anoxic brain injury that leads to premature mortality or long-term disabilities in infants. Neuroinflammation is a vital contributor to the pathogenic cascade post-HIE and a mediator to secondary neuronal death. As a plasma membrane G-protein-coupled receptor, GPR39, exhibits anti-inflammatory activity in several diseases. This study aimed to explore the neuroprotective function of GPR39 through inhibition of inflammation post-hypoxic-ischemic (HI) injury and to elaborate the contribution of sirtuin 1(SIRT1)/peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α)/nuclear factor, erythroid 2 like 2(Nrf2) in G-protein-coupled receptor 39 (GPR39)-mediated protection. METHODS: A total of 206 10-day-old Sprague Dawley rat pups were subjected to HIE or sham surgery. TC-G 1008 was administered intranasally at 1 h, 25 h, 49 h, and 73 h post-HIE induction. SIRT1 inhibitor EX527, GPR39 CRISPR, and PGC-1α CRISPR were administered to elucidate the underlying mechanisms. Brain infarct area, short-term and long-term neurobehavioral tests, Nissl staining, western blot, and immunofluorescence staining were performed post-HIE. RESULTS: The expression of GPR39 and pathway-related proteins, SIRT1, PGC-1α and Nrf2 were increased in a time-dependent manner, peaking at 24 h or 48-h post-HIE. Intranasal administration of TC-G 1008 reduced the percent infarcted area and improved short-term and long-term neurological deficits. Moreover, TC-G 1008 treatment significantly increased the expression of SIRT1, PGC-1α and Nrf2, but downregulated the expressions of IL-6, IL-1ß, and TNF-α. GPR39 CRISPR EX527 and PGC-1α CRISPR abolished GPR39's neuroprotective effects post-HIE. CONCLUSIONS: TC-G 1008 attenuated neuroinflammation in part via the SIRT1/PGC-1α/Nrf2 pathway in a neonatal rat model of HIE. TC-G 1008 may be a novel therapeutic target for treatment post-neonatal HIE injury.

5.
J Am Chem Soc ; 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34652140

RESUMO

The bottom-up approach to directly synthesizing low-dimensional materials with outstanding performance has extended the material basis for the next generation integrated circuit industry. All the low-dimensional semiconductors, metals, dielectrics, and their heterojunctions are very promising bricks to build faster and more efficient chips because of their atomically smooth surface and interfaces. The greatest challenge in the synthesis of nanomaterials is how to precisely control the structure, crystalline orientation, defects, dimensions, etc. In past decades, both the methodology and the mechanism of synthesis have been systematically investigated to improve the controllability. However, few studies focused on sensing the synthesis processes in situ and responding to the synthesis immediately. Here, we propose the concept of intelligent synthesis in which the final product can be automatically fine-controlled by a closed loop including in situ monitoring and real-time interventions. As a model system, a high-temperature-tolerant circuit is fabricated on the single-walled carbon nanotube (SWCNT) growth substrate for sensing and responding to the synthesis processes. As a result, either highly pure semiconducting (s-) SWCNT arrays or metallic-semiconducting (m-s) junction arrays with different junction positions is simply synthesized by programming the responding signal. The intelligent synthesis shows much higher efficiency and controllability compared to conventional methods and will lead to the next leap in nanotechnology.

6.
Clin Imaging ; 81: 15-23, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34597999

RESUMO

OBJECTIVE: To explore the value of amide proton transfer-weighted (APTw) magnetic resonance imaging (MRI) for differential diagnosis of fibroadenomas and malignant breast tumors. MATERIALS AND METHODS: This prospective study enrolled 56 patients with suspected breast tumors and performed APTw imaging. Based on the histopathology results, patients were divided into group 1 with malignant breast tumors (n = 41) and group 2 with fibroadenomas (n = 15). The measured image parameters (APTw value, ADC value, type of Time of Intensity Curve, maximum tumor diameter in image) and the maximal diameter of the tumors measured from surgical resection were compared between the two groups, and the diagnostic performance based on these parameters was quantified with ROC curve. Spearman's correlation coefficient was used to analyze the association between APTw or ADC values and ER, PR, HER2, and Ki-67 expressions. RESULTS: The intraclass correlation coefficients (ICC = 0.87 and 0.91) indicated a good inter-observer agreement of the measured APTw values. APTw values of malignant lesions were significantly higher than those of fibroadenomas (3.21 ± 1.04% vs 1.50 ± 0.54%, p < 0.001). Area under the curve (AUC) obtained from APTw imaging, DWI, DCE, APTw imaging+DWI, APTw imaging+DWI, and APTw imaging+DWI + DCE was 0.959, 0.897, 0.976, 0.997, and 1 respectively. The APTw value showed a negative correlation with ER expression (r = -0.357). CONCLUSION: APTw imaging yielded similar diagnosis performance in discriminating fibroadenomas and malignant breast tumors when compared to the DCE and better than DWI imaging, and provided supplement information on tumor cell activity to DWI images. The APTw value showed correlations with some prognostic factors for breast cancer.

7.
Mikrochim Acta ; 188(11): 373, 2021 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-34626231

RESUMO

Mercury ions (Hg2+) mediating in situ heterojunction formation strategy based on spatially separated dual working areas was developed to achieve sensitive detection of human immunoglobulin G. To be specific, the complex of antibody, the silicon dioxide, and thymine-rich hairpin DNA were immobilized onto the antigen and antibody-modified electrodes, forming a special sandwich type where T-Hg2+-T structure could accommodate Hg2+. The zinc ions from zinc sulfide (ZnS) photoelectric materials were captured by Hg2+ to convert ZnS to zinc sulfide-mercuric sulfide nanocomposite. Such ion exchange approach with spatially separated working electrodes endowed the sensing platform with lower background interference and high selectivity, which also avoided damage of illumination on biomolecules. In addition, by regulating the ion recognition probe, the protocol could be extended to numerous other fields like clinical diagnosis, environmental monitoring, and public safety.

8.
Front Public Health ; 9: 657804, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34490177

RESUMO

Objective: Our objective is to explore the effect of applying cloud video conferencing methods to the informed consent process in an early-phase clinical trial during the COVID-19 pandemic. Methods: All participants who intended to participate in the trial were informed via a cloud video conference before signing the informed consent forms (ICF). Then, the attitudes of the participants with the cloud video conference and their understanding of the trial were evaluated using a questionnaire when they visited to sign the ICF onsite. Results: A total of 165 subjects participated in the cloud video conference process, and 142 visited the site to sign and date the ICFs at the center during the appointment time. The survey showed that nearly 100% of the subjects evaluated the video-based informed consent process as very good or good and gave correct answers to questions about the trial. Furthermore, 136 (95.8%) subjects believed that the knowledge about the trial derived via the video-based informed consent process was consistent with the onsite reality, and 139 (97.9%) subjects expressed their willingness to participate in an informed consent procedure undertaken through an online video conference. Conclusions: The video-based informed consent process achieved the same effects as an onsite informed consent process. The former saves time and cost of transportation for the subject and exhibits good public acceptance; especially in light of the COVID-19 pandemic, this process is conducive for reducing the risk of subject infection due to travel and would also help avoid crowding on site.


Assuntos
COVID-19 , Pandemias , Voluntários Saudáveis , Humanos , SARS-CoV-2 , Comunicação por Videoconferência
9.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(9): 900-906, 2021 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-34487541

RESUMO

OBJECTIVE: To investigate the application value of whole exome sequencing technology in fetuses with congenital structural abnormalities. METHODS: The chromosomal abnormalities of 1147 families were analyzed. According to the follow-up results, the data of fetuses with new phenotypes in late pregnancy or after birth were reanalyzed. Subgroups were divided according to the organs involved and whether single malformation or not. The gene regulatory network map was drawn by using string database and Cytoscape software. Fisher exact probability method was used to compare the difference of the diagnostic rate of pathogenic genes among the groups. RESULTS: A total of 160 fetal cases received positive molecular diagnosed, involving 178 variant sites of 125 pathogenic genes, including 8 cases (4.9%, 8/163) by data reanalysis, and the overall positive diagnosis rate was 13.9%. Diagnostic rate was highest in the group of skeletal malformation (31.5%, 39/124) and lowest in that with thoracic malformation (0, 0/32). The gene clusters of fetal edema and intrauterine growth restriction were independent, and were not associated with the major structural malformations. The probability of each parent carrying the same recessive gene variant was 0.03 (39/1146) and 0.08 (4/53) with positive family history. CONCLUSION: For fetuses with congenital structural abnormalities that are negative for conventional genetic tests, 13.9% of phenotypic associated pathogenic/likely pathogenic genetic variants can be detected by whole exome sequencing technology. Its application value for prenatal diagnosis varies in fetus with different organs involved. Reanalysis of sequencing data for cases with new phenotypes in late pregnancy or after birth can further improve the molecular diagnosis rate. Further investigations are needed to explore the related genetic mechanisms.


Assuntos
Doenças Fetais , Feto , Feminino , Feto/diagnóstico por imagem , Humanos , Gravidez , Diagnóstico Pré-Natal , Tecnologia , Ultrassonografia Pré-Natal , Sequenciamento Completo do Exoma
10.
Artigo em Inglês | MEDLINE | ID: mdl-34495649

RESUMO

With the depletion of nonrenewable resources such as oil/coal/gas, more and more research studies began to focus on the high-value utilization of residual biomass resources. Herein, for the first time, honeycomb nanoporous microspheres fabricated from renewable biomass resources of cellulose were used as a carrier to fabricate a highly dispersed palladium (Pd) nanocatalyst. Various physicochemical characterizations presented convincing pieces of evidence for the good dispersion of Pd clusters with a mean diameter of 1.6 nm. As the carrier, cellulose microspheres with an interconnected nanoporous structure contributed to the adhesion and dispersion of Pd particles, and their rich hydroxyl groups could fix the Pd particles. Importantly, the cellulose matrix could in situ induce the formation of metallic Pd(0) during calcination without a reductant. The cellulose/Pd catalyst was applied to the Suzuki coupling reaction, which exhibited promising catalytic activity compared to commercial Pd/C and unsupported homogeneous Pd(OAc)2 catalysts, as well as good stability. The utilization of the residual biomass resource to build catalyst materials would be important for the sustainable chemistry.

11.
J Agric Food Chem ; 69(36): 10749-10759, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34474557

RESUMO

Gestational diabetes mellitus (GDM) not only has a bad effect on the development of infants but also causes variations in breastmilk composition. This study aims to investigate the changes in the protein profile of colostrum between mothers with GDM and healthy mothers (H) by sequential windowed acquisition of all theoretical fragment ion proteomics techniques. A total of 1295 proteins were detected, with 192 proteins being significantly different between GDM and H. These significantly different proteins were enriched with the carbohydrate and lipid metabolism pathway as well as immunity. Some proteins had an AOC value of 1, such as apolipoprotein E and lipoprotein lipase. In addition, we identified 42 glycated and 93 glycosylated peptides in colostrum without any enrichment, with glycated peptides being upregulated and glycosylated peptides being downregulated in colostrum with GDM. These results help us to better understand the GDM-induced changes in proteomes and glycated and glycosylated level and provide guidance on infant formula adjustment for infants from mothers with GDM.


Assuntos
Diabetes Gestacional , Colostro , Feminino , Humanos , Leite Humano , Gravidez , Proteoma , Proteômica
12.
Eur J Clin Nutr ; 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34531540

RESUMO

BACKGROUND: Newborn telomere length is considered as an effective predictor of lifespan and health outcomes in later life. Selenium is an essential trace element for human health, and its antioxidation is of great significance for the prevention of telomere erosion. METHODS: We recruited 746 mother-newborn pairs in Wuhan Children's Hospital between 2013 and 2015. Urine samples were repeatedly collected at three time points during pregnancy, and umbilical cord blood samples were collected right after parturition. Urinary selenium concentration was detected using inductively coupled plasma mass spectrometry, and newborn telomere length was measured using quantitative real-time polymerase chain reaction. We applied general estimating equations to examine the trimester-specific association between maternal urinary selenium during pregnancy and newborn telomere length. RESULTS: The median of creatinine-corrected selenium concentrations during pregnancy were 16.29, 18.08, and 18.35 µg/g·creatinine in the first, second, and third trimesters, respectively. Selenium concentrations in all the three trimesters were significantly associated with newborn telomere length. Per doubling of maternal urinary selenium concentrations was associated with 6.44% (95% CI: 0.92, 12.25), 6.54% (95% CI: 0.17, 13.31), and 6.02% (95% CI: 0.29, 12.09) longer newborn telomere length in the first, second, and third trimesters, respectively, after adjusting for potential confounders. CONCLUSIONS: This is the first study to provide evidence for the effect of maternal selenium levels on fetal telomere erosion. Findings from our study suggested that maternal urinary selenium was positively associated with newborn telomere length, indicating that intrauterine selenium exposure might have effect on initial setting of human telomere length.

13.
Anat Rec (Hoboken) ; 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34536264

RESUMO

This study aimed to uncover the potential mechanism of Erchen decoction (ECD) on the amelioration of nonalcoholic fatty liver disease (NAFLD). Network pharmacology and bioinformatics were used to determine the active components of ECD and its potential target in treating NAFLD. High fat diet (HFD)-induced NAFLD mice model was used. Liver tissues were stained with hematoxylin and eosin, and Oil Red O. Serum lipid profiles and hepatic inflammatory molecules in lipopolysaccharide (LPS)/Toll-like receptor-4 (TLR-4) pathway were confirmed by enzyme-linked immunosorbent assay. Intestinal barrier function, including intestinal epithelial tight junction (IETJ) proteins, fecal short-chain fatty acids (SCFAs) concentration and intestinal microbiota composition, was also assessed. Screening relevant databases revealed 123 active components and 158 potential target proteins in ECD, as well as 1,783 differential genes for NAFLD. Enrichment analyses predicted that the regulation of LPS, cholesterol metabolism and inflammatory pathways might be the underlying mechanisms of ECD in NAFLD treatment. ECD ameliorated the multi-profiles of NAFLD and reversed the high levels of inflammatory molecules such as, serum LPS, hepatic TLR-4, tumor necrosis factor-α, and interleukin-1ß. Additionally, ECD upregulated the concentration levels of IETJ proteins and fecal SCFAs. 16s RNA sequencing indicated that ECD can improve the gut microbiota, such as Akkermansia, Clostridium XIVa, Coprococcus, and Ruminococcus. The current study demonstrated that ECD can reverse the HFD-induced intestinal barrier dysfunction, thereby reducing the LPS translocation and alleviating the hepatic inflammation, and eventually exhibiting a protective effect against NAFLD.

14.
BMC Surg ; 21(1): 349, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34551734

RESUMO

BACKGROUND: To evaluate the feasibility and safety of a new minimally-invasive surgical approach-anteromedial minimally-invasive plate osteosynthesis (MIPO)-in the treatment of middle and distal humeral shaft fractures. METHODS: Fourteen patients with humeral shaft fracture treated with anteromedial MIPO from November 2016 to March 2020 (MIPO Group) were selected as the study subjects. Open reduction and internal fixation (ORIF) were used to treat 14 patients with humeral shaft fractures as the control group (ORIF group). The two groups were fixed with a locking compression plate (LCP) or LCP + multi-directional locking screw system (MDLS). The incision length, intraoperative blood loss, intraoperative fluoroscopy time, operation time, length of hospital stay, fracture healing time, QuickDASH score and Constant score were observed and compared between the two groups. RESULTS: Fourteen patients were enrolled in each group. The incision length (7.79 ± 2.39 cm), intraoperative blood loss (96.07 ± 14.96 mL), operative time (110.57 ± 21.90 min), hospital stay (6.29 ± 1.49 days) and fracture healing time (14.94 ± 0.99 weeks) in the MIPO group were all lower than those in the ORIF group, and the difference was statistically significant for each parameter (P < 0.05). The intraoperative fluoroscopy time (20.07 ± 3.22) in the MIPO group was significantly higher than that in the ORIF group (P < 0.05). There were no significant differences in age (P = 0.078), QuickDASH score (P = 0.074) or Constant score (P = 0.293) between the two groups and no postoperative complications occurred in any of the patients. CONCLUSION: The anteromedial approach MIPO technique has the advantages of less trauma, less bleeding, low risk of nerve injury and high rate of fracture healing. It is one of the most effective methods for the treatment of middle and middle-distal humeral shaft fractures.


Assuntos
Placas Ósseas , Fraturas do Úmero , Estudos de Casos e Controles , Fixação Interna de Fraturas , Consolidação da Fratura , Humanos , Fraturas do Úmero/cirurgia , Úmero , Procedimentos Cirúrgicos Minimamente Invasivos , Resultado do Tratamento
15.
Carbohydr Polym ; 273: 118547, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34560959

RESUMO

To meet the rising demand of injectable hydrogels with self-healing, robustness and biocompatibility for biomedical engineering, the reversible ketoester-type acylhydrazone linkages was used for the fabrication of novel cellulose-based hydrogel. The ketoester-type acylhydrazone bond exchanged rapidly, endowing the hydrogels with highly efficient self-healing performance without any external stimuli under physiological environment, which was hardly achieved with the widely used arylhydrozone bond. The dynamic hydrogels exhibited tunable mechanical property, pH responsiveness, injectability and biocompatibility, demonstrating immense applications prospect for various biomedicines, such as drug and cell delivery. The pH-responsive controlled release of model drug doxorubicin (DOX) loaded in the hydrogel was demonstrated. In addition, benefitting from the excellent biocompatibility and the reversible ketoester-type acylhydrazone bonds, cells were encapsulated in the hydrogels as 3D carrier. The covalent adaptable network intensified injectability of cell-laden hydrogels and improved the long-lasting viability for cell culture, showing great potential in the biomedical field.

16.
Int J Biol Macromol ; 191: 27-39, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34534578

RESUMO

Bacterial infection has become one of the most challenges for wound healing, which causes serious inflammatory response and delays the healing process. Herein, a novel sponge with excellent biocompatible, antibacterial and anti-inflammatory properties based on quaternized cellulose (QC), sodium alginate (SA) and Zn2+ was reported. The existence of physical interactions, such as electrostatic interaction, chelation and hydrogen bonding endowed the sponges with enhanced mechanical property. The composite sponges exhibited outstanding biocompatibility and hemostatic efficiency due to the compatible nature of the component and physical cross-linking, as well as superior antibacterial property benefited from the synergistic effects of steady Zn2+ release and quaternary ammonium group. In vivo investigation validated that the enhanced antibacterial and anti-inflammatory effect of the sponges, which significantly promoted wound closure and the reconstruction of skin tissue through epithelial regeneration, collagen deposition and mitigating inflammatory cell infiltration. Overall, the novel sponge demonstrated great potentials in bacteria-associated wound management.

17.
Stem Cell Res Ther ; 12(1): 444, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34365970

RESUMO

BACKGROUND: Age-associated changes attenuate human blood system functionality through the aging of hematopoietic stem and progenitor cells (HSPCs), manifested in human populations an increase in myeloproliferative disease and even leukemia; therefore, study on HSPC senescence bears great significance to treat hematopoietic-associated disease. Furthermore, the mechanism of HSPC aging is lacking, especially the cellular memory mechanism. Here, we not only reported a new HSPC senescence model in vitro, but also propose and verify the cellular memory mechanism of HSPC aging of the Polycomb/Trithorax system. METHODS: HSPCs (Lin-c-kit+ cells) were isolated and purified by magnetic cell sorting (MACS). The proportions and cell cycle distribution of cells were determined by flow cytometry; senescence-related ß-galactosidase assay, transmission electron microscope (TEM), and colony-forming unit (CFU)-mix assay were detected for identification of the old HSPC model. Proteomic tests and RNA-seq were applied to analyze differential pathways and genes in the model cells. qPCR, Western blot (WB), and chromatin immunoprecipitation PCR (CHIP-PCR) were used to detect the gene expression of cell memory-related proteins. Knockdown of cell memory-related key genes was performed with shRNA interference. RESULTS: In the model old HSPCs, ß-gal activity, cell cycle, colony-forming ability, aging-related cell morphology, and metabolic pathway were significantly changed compared to the young HSPCs. Furthermore, we found the model HSPCs have more obvious aging manifestations than those of natural mice, and IL3 is the major factor contributing to HSPC aging in the model. We also observed dramatic changes in the expression level of PRC/TrxG complexes. After further exploring the downstream molecules of PRC/TrxG complexes, we found that Uhrf1 and TopII played critical roles in HSPC aging based on the HSPC senescence model. CONCLUSIONS: These findings proposed a new HSPC senescence model in vitro which we forecasted could be used to preliminary screen the drugs of the HSPC aging-related hemopathy and suggested cellular memory mechanism of HSPC aging.


Assuntos
Células-Tronco Hematopoéticas , Proteômica , Animais , Senescência Celular , Ensaio de Unidades Formadoras de Colônias , Camundongos
18.
J Environ Manage ; 298: 113379, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34358934

RESUMO

Improving water use efficiency from a recycling perspective is claimed to be a better way to ensure prosperity in a water-stressed world. Although many studies have focused on the efficiency of integrated water use system, such as a water use and wastewater treatment (WUWT) system, few studies have observed the dynamic change involving a two-stage recycling structure. This research thus proposes a dynamic two-stage recycling model within the directional distance function (DDF) by taking reused water in the WT stage as a recycled product for WU stage's input in the next period. This paper reveals the dynamic evolution and spatial migration path of this efficiency in China. Results are as follows. (1) The average overall efficiency of the urban WUWT system for 30 provinces during 2011-2018 was 0.78. The central region's lower WUWT efficiency was caused by the expanding provincial differences in WU efficiency. (2) The urban WU sub-system performed poorer than that of the urban WT sub-system due to underutilizing reused water, such as in Jiangxi, Guangxi, Yunnan, and Jilin. (3) Narrowing the spatial imbalance of economic development and water use between the eastern and western regions is of great importance for promoting China's spatial imbalance of urban WUWT efficiency.


Assuntos
Desenvolvimento Econômico , Água , China , Eficiência , Reciclagem
19.
Stem Cell Res Ther ; 12(1): 450, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380544

RESUMO

BACKGROUND: Mesenchymal stem cells (MSCs) have a therapeutic effect on diabetic nephropathy (DN) but the underlying mechanism remains unclear. This study was conducted to investigate whether human umbilical cord-MSCs (hUCMSCs) can induce oxidative damage and apoptosis by activating Nrf2. METHODS: We used a type 2 diabetic rat model and a high-glucose and fat-stimulated human glomerular mesangial cell (hGMC) model. Western blotting, RT-qPCR, and TUNEL staining were performed on animal tissues and cultured cells. Nuclear expression of Nrf2 was detected in the renal tissue. Furthermore, Nrf2 siRNA was used to examine the effects of hUCMSCs on hGMCs. Finally, the effect of hUCMSCs on the Nrf2 upstream signalling pathway was investigated. RESULTS: After treatment with hUCMSCs, Nrf2 showed increased expression and nuclear translocation. After Nrf2-specific knockout in hGMCs, the protective effect of hUCMSCs on apoptosis induced by high-glucose and fat conditions was reduced. Activation of the PI3K signalling pathway may be helpful for ameliorating DN using hUCMSCs. CONCLUSIONS: hUCMSCs attenuated renal oxidative damage and apoptosis in type 2 diabetes mellitus and Nrf2 activation is one of the important mechanisms of this effect. hUCMSCs show potential as drug targets for DN.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Células-Tronco Mesenquimais , Animais , Apoptose , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/terapia , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/terapia , Humanos , Células-Tronco Mesenquimais/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Ratos , Cordão Umbilical/metabolismo
20.
Front Endocrinol (Lausanne) ; 12: 713849, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394007

RESUMO

Background and Aims: Several clinical trials have proved the efficacy of clopidogrel treatment for patients with percutaneous coronary intervention. There are few large-scale studies to identify the mortality associated with different durations of treatment of clopidogrel in patients with diabetes and ACS undergoing PCI in the Chinese population. The objective of this analysis was to determine the efficacy of long-term clopidogrel therapy (≥12 months) versus short-term use (<12 months) in Chinese patients with diabetes after PCI. Methods and Results: We used the Beijing Municipal Medical Insurance Database provided by the Beijing Municipal Medical Insurance Bureau. The Beijing Municipal Medical Insurance Database contained medical data of about 16 million people, including about 990,000 patients with diabetes and a history of taking antidiabetic medicines. Patients were divided into two groups, one group of 9,116 patients receiving consecutive clopidogrel for one year or more, and another group of 3290 patients receiving consecutive clopidogrel for less than one year. The primary outcomes of this analysis were the risk of all-cause death, myocardial infarction, and revascularization. In patients with diabetes after PCI, long-term clopidogrel treatment was associated with a reduced risk of all-cause death (HR, 0.57[95%CI, 0.49-0.67], P<0.0001), myocardial infarction (HR, 0.79[95%CI, 0.68-0.93], P=0.0035) and an increased risk of angina (HR, 1.18[95%CI, 1.10-1.27], P<0.0001]) and revascularization (HR, 1.07[95%CI, 1.01-1.13], P=0.02]). There was no significant difference in the prevalence of all-cause re-hospitalization, diabetes-related re-hospitalization, and cerebrovascular re-hospitalization. Conclusion: The present study concluded that long-term dual antiplatelet therapy including clopidogrel and aspirin could decrease the risks of all-cause death, myocardial infarction. But it could increase the risks of angina and revascularization. Further studies should interpret the cause of this question.

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