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1.
Scand J Gastroenterol ; : 1-11, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35512233

RESUMO

OBJECTIVE: To identify and utilize gene signatures for the prognostic evaluation of postoperative patients with hepatocellular carcinoma (HCC). METHODS: The gene mRNA expression profiles and corresponding clinicopathological data of postoperative patients with HCC were downloaded from The Cancer Genome Atlas (TCGA) database. Highly differentially expressed genes (DEGs) in tumor tissues compared to adjacent tissues were identified, and their associations with the overall survival (OS) of HCC patients were analyzed. The strongly associated genes were used to develop a prognostic score for the survival stratification of HCC, and the underlying mechanisms were analyzed using bioinformatics. RESULTS: A total of 376 DEGs were identified and four DEGs (ADH4, COL15A1, RET and KCNJ16) were independently associated with OS. A prognostic score derived from the four genes could effectively stratify HCC patients with different OS outcomes, independent of clinical parameters. Patients with high scores exhibited poorer OS than patients with low scores (HR 5.526, 95% CI: 2.451-12.461, p < .001). The four genes were involved in cancer-related biological processes and were independent of each other in bioinformatics analyses. CONCLUSION: Four genes strongly associated with the prognosis of postoperative patients with HCC were identified, and the derived prognostic score was simple and valuable for overall survival prediction.

2.
World J Clin Cases ; 10(9): 2751-2763, 2022 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-35434091

RESUMO

BACKGROUND: The exact definition of Acute kidney injury (AKI) for patients with traumatic brain injury (TBI) is unknown. AIM: To compare the power of the "Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease" (RIFLE), Acute Kidney Injury Network (AKIN), Creatinine kinetics (CK), and Kidney Disease Improving Global Outcomes (KDIGO) to determine AKI incidence/stage and their association with the in-hospital mortality rate of patients with TBI. METHODS: This retrospective study collected the data of patients admitted to the intensive care unit for neurotrauma from 2001 to 2012, and 1648 patients were included. The subjects in this study were assessed for the presence and stage of AKI using RIFLE, AKIN, CK, and KDIGO. In addition, the propensity score matching method was used. RESULTS: Among the 1648 patients, 291 (17.7%) had AKI, according to KDIGO. The highest incidence of AKI was found by KDIGO (17.7%), followed by AKIN (17.1%), RIFLE (12.7%), and CK (11.5%) (P = 0.97). Concordance between KDIGO and RIFLE/AKIN/CK was 99.3%/99.1%/99.3% for stage 0, 36.0%/91.5%/44.5% for stage 1, 35.9%/90.6%/11.3% for stage 2, and 47.4%/89.5%/36.8% for stage 3. The in-hospital mortality rates increased with the AKI stage in all four definitions. The severity of AKI by all definitions and stages was not associated with in-hospital mortality in the multivariable analyses (all P > 0.05). CONCLUSION: Differences are seen in AKI diagnosis and in-hospital mortality among the four AKI definitions or stages. This study revealed that KDIGO is the best method to define AKI in patients with TBI.

3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(2): 466-475, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35395981

RESUMO

OBJECTIVE: To investigate the toxicity management and efficacy evaluation of BCMA-chimeric antigen receptor T cells(CART) in the treatment of relapsed and refractory multiple myeloma (MM). METHODS: The efficacy and adverse reactions of 21 patients with MM who received BCMA-CART treatment at the First Affiliated Hospital of Wenzhou Medical University from December 2017 to September 2020 were evaluated, and the efficacy assessment and survival analysis for high-risk patients and non-high-risk patients were evaluated. RESULTS: After infusion of BCMA-CART cells in 21 MM patients, the number of effective cases was 17, of which the complete remission (sCR/CR) was 10, and the partial remission (VGPR/PR) was 7. The median OS time for all patients was 19.4 months, and the median PFS time was 7.9 months. The number of patients with extramedullary disease(EMD), high-risk genetics, and ISS stage Ⅲ were 5, 15 and 8, and the effective number was 3, 11 and 6, respectively. The treatment of 3 patients without high-risk factors was effective. The median OS and median PFS of patients with EMD were 14.2 and 2.5 months, respectively, which were shorter than those of patients without EMD (19.4 months and 8.9 months, respectively). The median OS and median PFS of patients with high-risk cytogenetic factors and ISS Ⅲ were not significantly different from those of non-high-risk patients. Cytokine release syndrane (CRS) occurred in 20 patients, of which 14 cases were Grade 1 CRS, while 6 were Grade 2, no CRS of Grade 3 or above occurred. IL-6 receptor inhibitors were used in 9 patients. All CRS were controlled effectively, and no patients had neurological toxicity. CONCLUSION: BCMA-CART is a certain curative effect in the treatment of relapsed and refractory multiple myeloma, and the adverse reactions can be well controlled through close monitoring and timely treatment.


Assuntos
Mieloma Múltiplo , Receptores de Antígenos Quiméricos , Antígeno de Maturação de Linfócitos B , Humanos , Imunoterapia Adotiva/efeitos adversos , Mieloma Múltiplo/terapia , Indução de Remissão
4.
RSC Adv ; 12(7): 3969-3978, 2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-35425441

RESUMO

In this study, we investigated the effect of sodium dodecyl sulfate (SDS) content on the structure and properties of chitosan films. It is found that the binding of SDS to chitosan was realized through the interactions between -SO4 - and -NH3 +, forming an ionically cross-linked film. Structural analysis revealed that the crystallization was greatly hindered by introducing SDS. With an increase of SDS content, the glass transition temperatures (T g) of chitosan films increased due to the formation of crosslinks. Compared to pure chitosan film, the composite films had lower content of moisture and possessed better thermal stability. In addition, the mechanical properties of the as-obtained composite films were closely related to the content of SDS, and were significantly improved in the biopolymer films with moderate SDS content. These results indicate that the microstructure as well as properties of the chitosan films can be regulated by adding SDS.

5.
Can J Infect Dis Med Microbiol ; 2022: 4899824, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35345870

RESUMO

The Candidate Phyla Radiation (CPR), as a newly discovered and difficult-to-culture bacterium, accounts for the majority of the bacterial domain, which may be related to various oral diseases, including dental caries. Restricted by laboratory culture conditions, there is limited knowledge about oral CPR. Advances in metagenomics provide a new way to study CPR through molecular biology. Here, we used metagenomic assembly and binning to reconstruct more and higher quality metagenome-assembled genomes (MAGs) of CPR from oral dental plaque. These MAGs represent novel CPR species, which differed from all known CPR organisms. Relative abundance of different CPR MAGs in the caries and caries-free group was estimated by mapping metagenomic reads to newly constructed MAGs. The relative abundance of two CPR MAGs was significantly increased in the caries group, indicating that there might be a relationship with caries activity. The detection of a large number of unclassified CPR MAGs in the dataset implies that the phylogenetic diversity of CPR is enormous. The results provide a reference value for exploring the ecological distribution and function of uncultured or difficult-to-culture microorganisms.

6.
Cell Death Dis ; 13(3): 281, 2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35351877

RESUMO

Podocyte damage mediated by in situ complement activation in the glomeruli is a key factor in the pathogenesis of membranous nephropathy (MN), but the molecular mechanism has not been fully elucidated. Pyroptosis is a special type of programmed cell death, mediate inflammatory response and induce tissue injury. However, it is not clear whether pyroptosis is involved in the development and progression of MN. Here, we report that pyroptosis plays an important role in promoting podocyte injury in MN. We first observed the occurrence of pyroptosis in the kidneys of MN patients and validated that complement stimulation triggered pyroptosis in podocytes and that inhibiting pyroptosis reversed complement-induced podocyte damage in vitro. In addition, stimulation of complement caused mitochondrial depolarization and reactive oxygen species (ROS) production in podocytes, and inhibition of ROS reversed complement-induced pyroptosis in podocytes. Interestingly, inhibition of pyroptosis in turn partially alleviated these effects. Furthermore, we also found the involvement of pyroptosis in the kidneys of passive Heymann nephritis (PHN) rats, and inhibitors of pyroptosis-related molecules relieved PHN-induced kidney damage in vivo. Our findings demonstrate that pyroptosis plays a critical role in complement-induced podocyte damage in MN and mitochondrial dysfunction is an important mechanism underlying this process. It provides new insight that pyroptosis may serve as a novel therapeutic target for MN treatment in future studies.


Assuntos
Glomerulonefrite Membranosa , Podócitos , Animais , Proteínas do Sistema Complemento/metabolismo , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulonefrite Membranosa/etiologia , Glomerulonefrite Membranosa/patologia , Humanos , Mitocôndrias/patologia , Podócitos/metabolismo , Piroptose , Ratos , Espécies Reativas de Oxigênio/metabolismo
7.
J Texture Stud ; 53(2): 296-306, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35103309

RESUMO

This study was to compare the results of texture analyzer with those of farinograph and extensograph and determine whether texture analyzer could be used to evaluate the processing quality of highland barley flour (HBF) dough sheet. The farinograph and extensograph tests were used to determine the reconstituted flour properties, a texture analyzer was applied to measure the tensile strength (TS) of HBF dough sheet, and the content of glutenin macropolymer (GMP), free sulfhydryl (-SH) and secondary structure of protein and microstructure in HBF dough sheet were investigated. Furthermore, correlations between these parameters were determined by regression analysis and Pearson correlation coefficient. It was suggested that the reconstituted flours with a higher gluten index showed a higher farinograph quality number (FQN) and greater maximum resistance to extension (Rm ). HBF dough sheets with higher gluten index possessed higher GMP and lower free -SH contents, a more ordered secondary structure of protein, resulting in a more compact gluten network and a stronger TS. The regression and correlation analysis showed that TS was positively correlated with FQN and Rm . In addition, it was significantly correlated with the content of GMP, -SH, secondary structure of protein and gluten network. It was concluded that texture analyzer could be an alternative approach to evaluate the processing quality of HBF dough sheet. Moreover, the gluten index of flours could be used to predict the processing quality of HBF dough sheet.


Assuntos
Hordeum , Farinha , Glutens/química , Triticum/química
8.
Insect Mol Biol ; 2022 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-35184330

RESUMO

The superfamily of short-chain dehydrogenases/reductases (SDRs) is crucial in biosynthetic and signalling pathways, in which the carbonyl reductases (CBRs) subfamily is important in the biosynthesis of tetrahydrobiopterin (BH4). BH4 is an essential coenzyme for animals, and its deficiency can lead to neurological diseases. There are few reports on CBRs involved in BH4 synthesis of silkworms, Bombyx mori. Here, we identified 67 SDR genes in B. mori (BmSDR) through whole genome survey for the first time. Based on bioinformatics analyses and KEGG verification, four BmCBRs that may be related to BH4 synthesis were further characterized and functionally analysed. The results showed these four genes were high expressed in the head and gonads of ah09 (a lem mutant with defective BH4 synthesis). Enzyme activity, BH4 content and the related gene expression levels after intracellular interference with BmCBR and the main catalytic enzymes sepiapterin reductase of B. mori (BmSpr) in the de novo pathway of BH4 showed BmCBR2 plays a role in the salvage pathway. BmCBR3 and BmCBR4 regulate BH4 synthesis through the alternative pathway. Among the four pathways of silkworm BH4 synthesis, the de novo pathway occupies the dominant position, followed by the alternative pathway and salvage pathway. According to the overexpression of BmCBR3 after interference with BmSpr, the BH4 content did not change significantly. It is speculated that BmCBR3 is located upstream of BmSpr. These results provide a theoretical basis for in-depth exploration of the role of BmSDR in B. mori and also provide clues for the research of other animal-related diseases.

9.
Int Urol Nephrol ; 2022 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-35133575

RESUMO

OBJECTIVE: To evaluate the clinical characteristics and outcomes of patients with nephropathy associated with POEMS syndrome who received novel agents in combination with dexamethasone therapy, and renal pathological changes based on repeat biopsy in some patients after these novel-agent-based therapies. METHODS: The records of patients with nephropathy associated with POEMS syndrome in a single hospital from May 2017 to February 2021 were retrieved and studied in detail. All the patients received four cycles of initial novel-agent-based regimens such as bortezomib and dexamethasone (BD) or thalidomide plus dexamethasone (TD) or lenalidomide plus dexamethasone (RD) treatment. We further evaluated the pathological efficacy of these novel agents by repeat renal biopsy. RESULTS: Twelve patients with an average age of 48.6 ± 8.3 years diagnosed with nephropathy associated with POEMS syndrome were enrolled in this study. The duration from disease onset to renal biopsy was 28(8.3 ~ 54.5) months. All patients achieved good clinical responses in different degree after four cycles of initial novel agents in combination with dexamethasone therapy. After the treatment with novel-agent-based regimens, the levels of proteinuria decreased in most patients and were negative in five patients. The levels of serum creatinine (SCr) decreased in ten patients. Serum M protein was negative in four patients and still positive in the other eight patients. The levels of serum vascular endothelial growth factor (VEGF) were detected in seven patients, which were all decreased. The levels of interleukin-6 (IL-6) were detected in eight patients, which were also decreased. Repeat biopsies were performed after four cycles of novel-agent-based therapies in four patients who were all treated with BD treatment. Mesangiolysis, mesangial cells proliferation, endothelial cells proliferation, subendothelial space widening and acute renal tubulointerstitial lesions improved, the chronic renal tubulointerstitial lesions were stable. CONCLUSIONS: Novel agents improved clinical manifestations in patients with nephropathy associated with POEMS syndrome. In addition, novel-agent-based regimens such as BD treatment improved renal pathological manifestations, which suggested that novel agents could improve renal prognosis of the patients from the perspective of renal pathology.

10.
Artigo em Inglês | MEDLINE | ID: mdl-35191949

RESUMO

CONTEXT: The associations of obesity and diabetic nephropathy (DN) in type 2 diabetes are inconsistent in observational studies, and causality remains unclear. OBJECTIVE: To explore the causal effect of body mass index (BMI) on DN, estimated glomerular filtration rate (eGFR), and proteinuria in type 2 diabetes by a two-sample Mendelian randomization analysis. METHODS: A total of 56 genetic variants were selected as instrumental variables for BMI in 158,284 participants from BioBank Japan, and their effects on DN risk, eGFR, and proteinuria were estimated in 3972 individuals with type 2 diabetes. Then, sex-stratified MR analysis was performed between BMI and DN. We selected generalized summary Mendelian randomization (GSMR) analysis as the primary method and six other robust methods to test MR assumptions. RESULTS: One standard deviation increase in BMI was causally associated with higher DN risk (OR, 3.76; 95% CI, 1.88-7.53; P < 0.001), and lower eGFR level (OR, 0.71; 95% CI, 0.59-0.86; P < 0.001). However, BMI was not causally associated with proteinuria (P = 0.22). Sex-stratified analyses indicated the causal effect of BMI on DN was stronger in women (OR, 14.81; 95% CI, 2.67-82.05; P = 0.002) than in men (OR, 3.48; 95% CI, 1.18-10.27; P = 0.02). Sensitivity analyses did not show evidence for violation of the MR assumptions. CONCLUSIONS: Genetic evidence showed that higher BMI levels were causally associated with increased risk of DN and decreased eGFR levels. Moreover, the increase in BMI level had a greater impact on DN risk in women.

11.
Nat Commun ; 13(1): 31, 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013217

RESUMO

Papillary renal cell carcinoma (pRCC) is the most heterogenous renal cell carcinoma. Patient survival varies and no effective therapies for advanced pRCC exist. Histological and molecular characterization studies have highlighted the heterogeneity of pRCC tumours. Recent studies identified the proximal tubule (PT) cell as a cell-of-origin for pRCC. However, it remains elusive whether other pRCC subtypes have different cell-of-origin. Here, by obtaining genome-wide chromatin accessibility profiles of normal human kidney cells using single-cell transposase-accessible chromatin-sequencing and comparing the profiles with pRCC samples, we discover that besides PT cells, pRCC can also originate from kidney collecting duct principal cells. We show pRCCs with different cell-of-origin exhibit different molecular characteristics and clinical behaviors. Further, metabolic reprogramming appears to mediate the progression of pRCC to the advanced state. Here, our results suggest that determining cell-of-origin and monitoring origin-dependent metabolism could potentially be useful for early diagnosis and treatment of pRCC.


Assuntos
Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Cromatina , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Rim/patologia , Biomarcadores Tumorais , Carcinoma Papilar/patologia , Carcinoma de Células Renais/genética , Proteínas de Ligação a DNA , Epigenômica , Humanos , Neoplasias Renais/genética , Medicina Molecular , Fatores de Transcrição
12.
Beilstein J Org Chem ; 18: 25-36, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35047080

RESUMO

Bifunctional thiourea-catalyzed asymmetric [3 + 2] annulation reactions of 2-isothiocyanato-1-indanones with barbiturate-based olefins have been developed to afford chiral dispiro[indene-pyrrolidine-pyrimidine]s. Through this strategy, the target products could be obtained in good to excellent yields with excellent stereoselectivities. In addition, the synthetic utility was verified through a gram-scale synthesis, one-pot three-component reactions and further transformation experiments of the products.

13.
Bioengineered ; 13(2): 2114-2129, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35034547

RESUMO

Long noncoding RNAs (lncRNAs) have vital roles in the progression of colorectal cancer (CRC). Forkhead box P4-antisense RNA 1 (FOXP4-AS1) showed a potential unfavorable prognostic factor for CRC, while its underlying mechanism remains elusive. Thus, the goal of this research is to determine mechanism of FOXP4-AS1 in CRC occurrence and development. Herein, a Dual-luciferase reporter assay was performed to assess the regulation of miR-423-5p to nucleus accumbens-associated protein 1 (NACC1) and activating transcription factor 3 (ATF3) to FOXP4-AS1 promoter. Hematoxylin-eosin (H&E) staining was performed to detect the pathological changes of tumor tissues. Flow cytometry, cell counting kit 8, Transwell, and wound healing assays were conducted to assess apoptosis, proliferation, migration, and invasion of CRC cells, respectively. The results showed that FOXP4-AS1 was highly expressed in CRC cell lines and tissues. CRC progression was promoted by the overexpression of FOXP4-AS1 in HTC116 cells and animal models. Furthermore, FOXP4-AS1 served as a molecular sponge for miR-423-5p, and NACC1 is a direct target of miR-423-5p. MiR-423-5p silencing or overexpression of NACC1 increased proliferation, migration, and invasion of HCT116 cells while suppressing apoptosis. We also found that the upregulation of FOXP4-AS1 was activated by ATF3 in CRC cells. Collectively, our results demonstrated that ATF3-activated FOXP4-AS1 aggravates CRC progression by regulating miR-423-5p/NACC1 axis, indicating a new target for CRC treatment.


Assuntos
Fator 3 Ativador da Transcrição/metabolismo , Neoplasias Colorretais/metabolismo , MicroRNAs/metabolismo , Proteínas de Neoplasias/metabolismo , RNA Longo não Codificante/metabolismo , RNA Neoplásico/metabolismo , Proteínas Repressoras/metabolismo , Transdução de Sinais , Fator 3 Ativador da Transcrição/genética , Animais , Neoplasias Colorretais/genética , Células HCT116 , Células HT29 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Proteínas de Neoplasias/genética , RNA Longo não Codificante/genética , RNA Neoplásico/genética , Proteínas Repressoras/genética
14.
J Physiol Biochem ; 2022 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-35064467

RESUMO

Atherosclerosis (AS) is a chronic inflammatory disease characterized by abnormal lipid metabolism. Foam cell formation is also known as an early event of AS. Cholesterol efflux is a process whereby cholesterol is excreted from foam cells through transporters, which serves as one of the effective regulatory mechanisms to prevent AS. Autophagy is a biodegradable mechanism, and lipophagy is a special form of autophagy that selectively degrades lipids. Cholesterol efflux is regulated by several mechanisms. Moreover, numerous studies have shown that autophagy is also process whereby cholesterol efflux is regulated. In early studies, scholars found that cholesterol efflux is related to autophagy. Subsequent studies have shown that various targeted molecules can induce autophagy and promote the expression of cholesterol transporters (such as LXRα, ABCA1, and ABCG1) through specific signaling pathways. Several novel treatments for AS use these small molecules as entry points for research and development based on autophagy. However, this autophagy-dependent cholesterol efflux involves many different molecular mechanisms. This not only indicates that cholesterol efflux is the result of multiple factors, but also that autophagy, which mediates cholesterol efflux, is a complex physiological mechanism. Through a literature review, we found that the role of autophagy in cholesterol efflux is related to cell type and is regulated by both the level of autophagy and the mechanism that triggers autophagy. In this review, we aim to discuss the role of autophagy in cholesterol efflux from many aspects based on recent relevant studies to aid in the treatment of AS.

15.
ACS Nano ; 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34995440

RESUMO

The controlled growth of metallic single-wall carbon nanotubes (m-SWCNTs) is very important for the fabrication of high-performance interconnecting wires, transparent conductive electrodes, light and conductive fibers, etc. However, it has been extremely difficult to synthesize m-SWCNTs due to their lower abundance and higher chemical reactivity than semiconducting SWCNTs (s-SWCNTs). Here, we report the kinetically controlled growth of m-SWCNTs by manipulating their binding energy with the catalyst and promoting their growth rate. We prepared CoRe4 nanoparticles with a hexagonal close-packed structure and an average size of ∼2.3 nm, which have a lower binding energy with m-SWCNTs than with s-SWCNTs. The selective growth of m-SWCNTs from the CoRe4 catalyst was achieved by using a low concentration of carbon source feed at a relative low temperature of 760 °C. The m-SWCNTs had a narrow diameter distribution of 1.1 ± 0.3 nm, and their content was over 80%.

16.
Angew Chem Int Ed Engl ; 61(1): e202113073, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34807499

RESUMO

Fluorescent single crystals that respond to multiple external stimuli are of great interest in molecular machines, sensors, and displays. The integration of photo- or acid-induced fluorescence enhancement and bending in one organic crystal, however, has not been reported yet. Herein, we report the interesting plastic photomechanical bending and switching on of the fluorescence of an azine crystal in a single-crystal transformation, due to extended π-conjugation and molecular slippage. Moreover, the fluorescent plastic bending driven by multiple volatile acid vapors was firstly observed, and attributed to the synergistic effect of push-pull electronic structure and hydrogen bonding. The single crystal also shows high elasticity under external force. In addition, reversible fluorescence switching can be triggered by grinding and solvent fuming, as well as by the adsorption and desorption of HCl vapor. The integration of plastic, elastic bending and switch-on fluorescence into one single crystal provides a new strategy for next-generation smart materials.

17.
Front Immunol ; 12: 720877, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34867948

RESUMO

Objectives: Combination therapy with mycophenolate mofetil, tacrolimus and steroids are effective in achieving complete remission in lupus nephritis (LN). Combination therapy uniquely downregulated caspase-1 compared with monotherapies, which can cleave gasdermin D (GSDMD) and was recently identified as the pyroptosis executioner. We therefore investigated whether combination therapy enabled the suppression of caspase-1/GSDMD-mediated pyroptosis in LN. Methods: Expression and activation of GSDMD were detected in kidney specimens of the human and mouse with LN using immunohistochemical staining and immunoblotting. Primary podocytes isolated from MRL/lpr mice were incubated with LPS+ATP, and pretreated with monotherapy or combination therapy. Inhibition of caspase-1/GSDMD-induced pyroptosis by combination therapy were assessed in MRL/lpr mice and human specimens. Pyroptosis was examined using a FAM caspase-1 kit and flow cytometry. The correlation between pyroptosis in peripheral blood and the systemic lupus erythematosus disease activity index (SLEDAI) was analyzed. Results: Kidney tissue specimens from LN patients and mice exhibited greatly increased expression levels and cleavage of GSDMD. In cultured podocytes, combination treatment significantly suppressed the activation of NLRP3 and caspase-1 and reduced GSDMD N-terminal levels. Combination therapy repressed disease progression through inhibition of caspase-1/GSDMD-mediated pyroptosis in both humans and MRL/lpr mice. Caspase-1/PI positive cell numbers in peripheral blood were positively correlated with SLE-DAI. LN patients with complete remission and partial remission had remarkably reduced caspase-1/PI positive cell numbers compared to baseline. Ac-FLTD-CMK, a GSDMD-derived inhibitor, prevented the development of LN. Conclusion: Combination therapy suppressed caspase-1/GSDMD-mediated pyroptosis in vitro and in vivo and reduced disease progression.


Assuntos
Inibidores de Caspase/administração & dosagem , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Nefrite Lúpica/tratamento farmacológico , Proteínas de Ligação a Fosfato/antagonistas & inibidores , Adolescente , Adulto , Idoso , Animais , Inibidores de Calcineurina/administração & dosagem , Caspase 1/efeitos dos fármacos , Células Cultivadas , Estudos de Coortes , Modelos Animais de Doenças , Quimioterapia Combinada , Feminino , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Nefrite Lúpica/metabolismo , Nefrite Lúpica/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos MRL lpr , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Podócitos/efeitos dos fármacos , Podócitos/metabolismo , Podócitos/patologia , Prednisona/administração & dosagem , Piroptose/efeitos dos fármacos , Tacrolimo/administração & dosagem , Adulto Jovem
18.
Science ; 374(6575): 1616-1620, 2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-34941420

RESUMO

Carbon nanotubes have a helical structure wherein the chirality determines whether they are metallic or semiconducting. Using in situ transmission electron microscopy, we applied heating and mechanical strain to alter the local chirality and thereby control the electronic properties of individual single-wall carbon nanotubes. A transition trend toward a larger chiral angle region was observed and explained in terms of orientation-dependent dislocation formation energy. A controlled metal-to-semiconductor transition was realized to create nanotube transistors with a semiconducting nanotube channel covalently bonded between a metallic nanotube source and drain. Additionally, quantum transport at room temperature was demonstrated for the fabricated nanotube transistors with a channel length as short as 2.8 nanometers.

19.
Front Cell Dev Biol ; 9: 733831, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34805144

RESUMO

Tubular cell senescence is a common biologic process and contributes to the progression of chronic kidney disease (CKD); however, the molecular mechanisms regulating tubular cell senescence are poorly understood. Here, we report that integrin ß3 (ITGB3) expression was increased in tubular cells and positively correlated with fibrosis degree in CKD patients. ITGB3 overexpression could induce p53 pathway activation and the secretion of TGF-ß, which, in turn, resulted in senescent and profibrotic phenotype change in cultured tubular cells. Moreover, according to the CMAP database, we identified isoliquiritigenin (ISL) as an agent to inhibit ITGB3. ISL treatment could suppress Itgb3 expression, attenuate cellular senescence, and prevent renal fibrosis in mice. These results reveal a crucial role for integrin signaling in cellular senescence, potentially identifying a new therapeutic direction for kidney fibrosis.

20.
Sci Total Environ ; 801: 149697, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34467921

RESUMO

Land use conflict describes the incoordination of land use structure when meeting the diverse human demands under the deterioration of natural environment, which is a sensitive indicator of human-environmental interaction. The increased demand for different land use types due to rapid population growth and urbanization in China places tremendous pressure on limited land resources, which raises great concerns about land use conflict. To solve them, nation-scale assessment is essential, but such kind of research is still lacking due to the high data requirements. Here we drew on the conceptual framework of ecological risk assessment and the theories in landscape ecology, and developed a methodology to derive the spatio-temporal patterns of land use conflict in China from 2001 to 2017. We then used multilevel regression model to identify the driving factors of land use conflict at different levels. The results showed that the areas with strong land use conflict had a higher frequency of land use change, indicating that our model based on the framework of ecological risk assessment could effectively measure land use conflict. Land use conflict showed significant differences between two sides of the Hu Huanyong line, an important division line of population density and socio-economic background. The Main types of land use conflict in China included the strong competition between the use of cultivated land and grassland, the rapid expansion of construction land and the high risk of desertification. Among the driving forces, population density had a positive impact on land use conflict at the upper level, and altitude had a negative impact at the bottom level. Our research provides essential information to solve land use conflict through scientific land use planning and management and further to achieve the sustainable use of land resources.


Assuntos
Conservação dos Recursos Naturais , Urbanização , China
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