Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.632
Filtrar
1.
J Hazard Mater ; 443(Pt A): 130142, 2023 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-36265378

RESUMO

Lipid peroxidation is a primary event in plant roots exposed to aluminum (Al) toxicity, which leads to the formation of reactive aldehydes. Current evidence demonstrates that the resultant aldehydes are integrated components of cellular damage in plants. Here, we investigated the roles of aldehydes in mediating Al-induced damage, particularly cell death, using two wheat genotypes with different Al resistances. Aluminum treatment significantly induced cell death, which was accompanied by decreased root activity and cell length. Al-induced cell death displayed granular nuclei and internucleosomal fragmentation of nuclear DNA, suggesting these cells underwent programmed cell death (PCD). During this process, caspase-3-like protease activity was extensively enhanced and showed a significant difference between these two wheat genotypes. Further experiments showed that Al-induced cell death was positively correlated with aldehydes levels. Al-induced representative diagnostic markers for PCD, such as TUNEL-positive nuclei and DNA fragmentation, were further enhanced by the aldehyde donor (E)-2-hexenal, but significantly suppressed by the aldehyde scavenger carnosine. As the crucial executioner of Al-induced PCD, the activity of caspase-3-like protease was further enhanced by (E)-2-hexenal but inhibited by carnosine in wheat roots. These results suggest that reactive aldehydes sourced from lipid peroxidation mediate Al-initiated PCD probably through activating caspase-3-like protease in wheat roots.


Assuntos
Alumínio , Carnosina , Alumínio/toxicidade , Peróxidos Lipídicos/metabolismo , Triticum/genética , Triticum/metabolismo , Caspase 3/metabolismo , Carnosina/metabolismo , Raízes de Plantas/metabolismo , Apoptose , Aldeídos/toxicidade , Aldeídos/metabolismo
2.
Food Chem ; 400: 134067, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36084594

RESUMO

To determine gentamicin residues in animal tissues, a monoclonal antibody (Mab) was produced and a sensitive indirect competitive chemiluminescent enzyme immunoassay (icCLEIA) was developed. At first, gentamicin was conjugated with bovine serum albumin as immunogens which were used to immunize BALB/c mice. Then, an anti-gentamicin Mab was prepared by hybridoma technology. Finally, a sensitive icCLEIA was developed with an 50% inhibition concentration (IC50) of 0.067 ng/mL for gentamicin. The limit of detection of the icCLEIA was 0.002 ng/mL. The cross reactivity of the Mab with structural analogues were<0.01%. The recoveries of gentamicin ranged from 80 to 101% and coefficient of variation was <6.4% in pork and fish samples. Samples were detected by UPLC-MS/MS for evaluating reliability of the icCLEIA. The results suggested that the prepared anti-gentamicin Mab can be used for rapid and convenient immunoassays to detect gentamicin residues in animal tissues.


Assuntos
Anticorpos Monoclonais , Gentamicinas , Animais , Cromatografia Líquida , Ensaio de Imunoadsorção Enzimática/métodos , Imunoensaio/métodos , Técnicas Imunoenzimáticas , Luminescência , Camundongos , Camundongos Endogâmicos BALB C , Reprodutibilidade dos Testes , Soroalbumina Bovina , Espectrometria de Massas em Tandem
3.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 39(11): 1233-1237, 2022 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-36317209

RESUMO

OBJECTIVE: To explore the molecular pathogenesis of a Chinese pedigree affected with inherited protein C (PC) deficiency. METHODS: The protein C activity (PC:A) and protein C antigen (PC:Ag) of the proband and his family members were determined by a chromogenic substrate method and enzyme-linked immunosorbent assay, respectively. The proband was subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing of other members of the pedigree. RESULTS: The PC:A and PC:Ag of proband were reduced to 15% and 11%, respectively. The above parameters of his parents and elder sister were also decreased to approximately 50% of reference values. Next generation sequencing has revealed that the proband has harbored a heterozygous c.572_574delAGA (p.Glu191_Lys192delinsGlu) variant in exon 7 and a missense c.752C>T (p.Ala251Val) variant in exon 8 of the PROC gene. His father was heterozygous for the c.572_574delAGA variant, while his mother and elder sister were heterozygous for the c.752C>T variant. According to the American College of Medical Genetics and Genomics Standards and Guidelines, the c.572_574delAGA (p.Glu191_Lys192 delinsGlu) variant was predicted to be likely pathogenic (PS1+PM4+PP3). c.752 C>T (p.Ala251Val) variant was also likely pathogenic (PS1+PM1+PP3). CONCLUSION: The deletional variant of c.572_574delAGA (p.Glu191_Lys192delinsGlu) in exon 7 and missense variant c.752C>T (p.Ala251Val) in exon 8 of the PROC gene probably underlay the inherited protein C (PC) deficiency in this pedigree. Above finding has enriched the spectrum of PROC gene variants and provided a basis for genetic counseling for this pedigree.


Assuntos
Deficiência de Proteína C , Humanos , China , Mutação , Linhagem , Proteína C/genética , Deficiência de Proteína C/genética , Masculino , Feminino
4.
Heliyon ; 8(10): e11229, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36325141

RESUMO

According to clinical investigations, sleep disruption (SD) can influence the immune system and cause inflammatory bowel disease (IBD). However, the detailed effects of sleep on IBD development and progression have not been clarified. Here, we used dextran sulfate sodium (DSS) to induce colitis in mice, and then interfered with SD (day-time 8:00 a.m. to 5:00 p.m.) to explore the influence of sleep on colitis by analyzing colon length, mouse body weight, disease activity index (DAI) score, pathology detection, and infiltration of inflammatory cells with LCA immunohistochemistry analysis. Next, we detected the mRNA levels of circadian genes and related inflammatory factors, including Bmal1, CLOCK, Cry1, Cry2, Per1, Per2, Timeless, Rev-erbα, TNF-α, IL-6, and IFN-γ. Additionally, we conducted a sleep survey in IBD patients and collected colon lesion sites to detect the mRNA levels of those eight circadian genes and three inflammatory factors. We found that SD promoted the body weight decrease, increased inflammation as shown with pathological staining of the DSS animal model, and increased expression of the clock gene Cry2 in DSS-induced colitis mice. In IBD patients with active disease, the mRNA level of circadian genes Bmal1, Cry1, Cry2, and Rev-erbα in inflammatory tissues decreased significantly compared with non-inflammatory tissues.

5.
J Rheumatol ; 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36319017

RESUMO

OBJECTIVE: Rheumatology patients are at high risk for complications from pneumococcal infections. The goal of this study was to assess the feasibility of implementing a nurse-driven pneumococcal vaccination protocol based on the 2012 Advisory Committee on Immunization Practices guidelines within an academic rheumatology clinic. Our aims were to increase 1) PCV13 and PPSV23 monthly vaccination rates in immunosuppressed patients aged 19-64 years and 2) the overall proportion of immunosuppressed patients aged 19-64 years who have received both PCV13 and PPSV23 vaccinations by ≥10% over a two-year period. METHODS: We identified eligible adults in the Electronic Medical Record using a search protocol based on pre-set medication group. We obtained baseline pneumococcal vaccination rates in 2019, calculating the proportion of patients who were unvaccinated, partially vaccinated (received either PCV13 or PPSV23), or fully vaccinated. We created a pneumococcal vaccination protocol based on 2012 ACIP guidelines and converted it into a Standing Medical Order to be implemented by the nursing staff. Post-intervention vaccination rates were calculated monthly and at the end of the study period. Multiple comparison testing was performed to assess for significant post-intervention changes. RESULTS: The average rate of monthly vaccination with either PCV13 or PPSV23 increased from 4.3% in 2019 to 12.6% in 2021. Proportion of patients who were fully vaccinated increased from 14.6% in 2019 to 26.2% in 2021. Both changes were statistically significant. CONCLUSION: It is feasible to employ a nurse-driven protocol for improving pneumococcal vaccination rates in immunosuppressed patients, despite difficulties posed by COVID-19 pandemic disruptions.

6.
Chaos ; 32(10): 103111, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36319282

RESUMO

A complex network has been widely used to reveal the rule of a complex system. How to convert the stock data into a network is an open issue since the stock data are so large and their random volatility is strong. In this paper, a seasonal trend decomposition procedure based on the loess ( S T L) method is applied to convert the stock time series into a directed and weighted symbolic network. Three empirical stock datasets, including the closing price of Shanghai Securities Composite Index, S&P 500 Index, and Nikkei 225 Index, are considered. The properties of these stock time series are revealed from the topological characteristics of corresponding symbolic networks. The results show that: (1) both the weighted indegree and outdegree distributions obey the power-law distribution well; (2) fluctuations of stock closing price are revealed by related network topological properties, such as weighting degree, betweenness, pageranks, and clustering coefficient; and (3) stock closing price, in particular, periods such as financial crises, can be identified by modularity class of the symbolic networks. Moreover, the comparison between the S T L method and the visibility graph further highlights the advantages of the S T L method in terms of the time complexity of the algorithm. Our method offers a new idea to study the network conversion of stock time series.

7.
J Health Psychol ; : 13591053221129705, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36325980

RESUMO

Overeating for non-homeostatic needs contributes to childhood obesity. However, validated measures or eating motives and cross-cultural comparisons are limited. This study aimed to validate the Kids-Palatable Eating Motives Scale (K-PEMS) and its association with body mass index z score (BMIz) in China, and further assess its generalization across Chinese and American youth. Data were from participants aged 8-18 years from Hangzhou, China (n = 426) and Birmingham, AL, U.S (n = 73). The K-PEMS had sound reliability and validation (Cronbach's α = 0.920 and all factor loadings >0.50) in the Chinese sample. Multi-group nested models CFAs showed that the ∆CFI of model comparisons of measurement weights and structural covariance, variance, and means were ⩽0.01, and ∆TLI of measurement intercepts ⩽0.05. Linear regressions revealed that frequency of consuming palatable foods and drinks for Coping, Reward Enhancement, and Conformity, but not Social motives, were positively associated with BMIz. The K-PEMS had good cross-cultural generalization and could be useful in treating obesity by identifying specific motives for consuming excessive calories.

8.
Crit Rev Food Sci Nutr ; : 1-15, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36377729

RESUMO

Enterohemorrhagic Escherichia coli is considered one of the primary bacterial pathogens that cause foodborne diseases because it can survive in meat, vegetables and so on. Understanding of the effect of vegetable characteristics on the adhesion and proliferation process of EHEC is necessary to develop control measures. In this review, the amount and methods of adhesion, the internalization pathway and proliferation process of EHEC have been described during the vegetable contamination. Types, cultivars, tissue characteristics, leaf age, and damage degree can affect EHEC adhesion on vegetables. EHEC cells contaminate the root surface of vegetables through soil and further internalize. It can also contaminate the stem scar tissue of vegetables by rain or irrigation water and internalize the vertical axis, as well as the stomata, necrotic lesions and damaged tissues of vegetable leaves. After EHEC adhered to the vegetables, they may further proliferate and form biofilms. Leaf and fruit tissues were more sensitive to biofilm formation, and shedding rate of biofilms on epidermis tissue was faster. Insights into the mechanisms of vegetable contamination by EHEC, including the role of exopolysaccharides and proteins responsible for movement, adhesion and oxidative stress response could reveal the molecular mechanism by which EHEC contaminates vegetables.

9.
Acta Pharmacol Sin ; 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36347997

RESUMO

Previous studies have shown mitochondrial dysfunction in various acute kidney injuries and chronic kidney diseases. Lipoic acid exerts potent effects on oxidant stress and modulation of mitochondrial function in damaged organ. In this study we investigated whether alpha lipoamide (ALM), a derivative of lipoic acid, exerted a renal protective effect in a type 2 diabetes mellitus mouse model. 9-week-old db/db mice were treated with ALM (50 mg·kg-1·d-1, i.g) for 8 weeks. We showed that ALM administration did not affect blood glucose levels in db/db mice, but restored renal function and significantly improved fibrosis of kidneys. We demonstrated that ALM administration significantly ameliorated mitochondrial dysfunction and tubulointerstitial fibrotic lesions, along with increased expression of CDX2 and CFTR and decreased expression of ß-catenin and Snail in kidneys of db/db mice. Similar protective effects were observed in rat renal tubular epithelial cell line NRK-52E cultured in high-glucose medium following treatment with ALM (200 µM). The protective mechanisms of ALM in diabetic kidney disease (DKD) were further explored: Autodock Vina software predicted that ALM could activate RXRα protein by forming stable hydrogen bonds. PROMO Database predicted that RXRα could bind the promoter sequences of CDX2 gene. Knockdown of RXRα expression in NRK-52E cells under normal glucose condition suppressed CDX2 expression and promoted phenotypic changes in renal tubular epithelial cells. However, RXRα overexpression increased CDX2 expression which in turn inhibited high glucose-mediated renal tubular epithelial cell injury. Therefore, we reveal the protective effect of ALM on DKD and its possible potential targets: ALM ameliorates mitochondrial dysfunction and regulates the CDX2/CFTR/ß-catenin signaling axis through upregulation and activation of RXRα. Schematic figure illustrating that ALM alleviates diabetic kidney disease by improving mitochondrial function and upregulation and activation of RXRα, which in turn upregulated CDX2 to exert an inhibitory effect on ß-catenin activation and nuclear translocation. RTEC renal tubular epithelial cell. ROS Reactive oxygen species. RXRα Retinoid X receptor-α. Mfn1 Mitofusin 1. Drp1 dynamic-related protein 1. MDA malondialdehyde. 4-HNE 4-hydroxynonenal. T-SOD Total-superoxide dismutase. CDX2 Caudal-type homeobox transcription factor 2. CFTR Cystic fibrosis transmembrane conductance regulator. EMT epithelial mesenchymal transition. α-SMA Alpha-smooth muscle actin. ECM extracellular matrix. DKD diabetic kidney disease. Schematic figure was drawn by Figdraw ( www.figdraw.com ).

10.
Pharmaceuticals (Basel) ; 15(11)2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36355541

RESUMO

Cancer stem cells (CSCs) are a subpopulation of cancer cells possessing stemness characteristics that are closely associated with tumor proliferation, recurrence and resistance to therapy. Recent studies have shown that different cytoskeletal components and remodeling processes have a profound impact on the behavior of CSCs. In this review, we outline the different cytoskeletal components regulating the properties of CSCs and discuss current and ongoing therapeutic strategies targeting the cytoskeleton. Given the many challenges currently faced in targeted cancer therapy, a deeper comprehension of the molecular events involved in the interaction of the cytoskeleton and CSCs will help us identify more effective therapeutic strategies to eliminate CSCs and ultimately improve patient survival.

11.
J Poult Sci ; 59(4): 323-327, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36382061

RESUMO

Body measurement traits (BMTs), which are classical quantitative traits of vital responses to body growth, have been studied in pigs, cattle, and sheep for several decades. In chickens, BMTs mainly cover body slope length, keel length, chest width, chest depth, tibia length, and tibia diameter; however, their genetic markers are yet to be considered. In this study, the Wenshang Barred chicken, a meat-egg-type native breed in China, was used to investigate the association between BMTs and the expression of growth-related genes, including GH, IGF1, IGF2, GHRL, IGF1R, IGFBP2, GHF-1, and TSHB. The results revealed that the single nucleotide polymorphism (SNP) rs3138025 in GH was significantly associated with keel length (P=0.0455 <0.05), rs313810945 in IGF2 was significantly correlated with chest width (P=0.0454 <0.05) and chest depth (P=0.0259 <0.05), and rs317298536 in TSHB significantly affected chest depth (P=0.0399 <0.05). The SNPs were associated with traits reflecting body size and were potentially involved in bone growth, which was consistent with studies in humans, rodents, and other vertebrate species. In addition, a borderline significant association was found between rs317298536 and body weight (P=0.0604). These polymorphic sites may be treated as candidate genetic markers in breeding programs involving Wenshang Barred chickens.

12.
Materials (Basel) ; 15(21)2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36363305

RESUMO

Two-dimensional (2D) materials are no doubt the most widely studied nanomaterials in the past decade. Most recently, a new type of 2D material named the double-layer honeycomb (DLHC) structure opened a door to achieving a series of 2D materials from traditional semiconductors. However, as a newly developed material, there still lacks a timely understanding of its structure, property, applications, and underlying mechanisms. In this review, we discuss the structural stability and experimental validation of this 2D material, and systematically summarize the properties and applications including the electronic structures, topological properties, optical properties, defect engineering, and heterojunctions. It was concluded that the DLHC can be a universal configuration applying to III-V, II-VI, and I-VII semiconductors. Moreover, these DLHC materials indeed have exotic properties such as being excitonic/topological insulators. The successful fabrication of DLHC materials further demonstrates it is a promising topic. Finally, we summarize several issues to be addressed in the future, including further experimental validation, defect engineering, heterojunction engineering, and strain engineering. We hope this review can help the community to better understand the DLHC materials timely and inspire their applications in the future.

13.
Adv Sci (Weinh) ; : e2204849, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36354175

RESUMO

Centenarians, who show mild infections and low incidence of tumors, are the optimal model to investigate healthy aging. However, longevity related immune characteristics has not been fully revealed largely due to lack of appropriate controls. In this study, single-cell transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) derived from seven centenarians (CEN), six centenarians' offspring (CO), and nine offspring spouses or neighbors (Control, age-matched to CO) are performed to investigate the shared immune features between CEN and CO. The results indicate that among all 12 T cell clusters, the cytotoxic-phenotype-clusters (CPC) and the naïve-phenotype-clusters (NPC) significantly change between CEN and ontrol. Compared to Control, both CEN and CO are characterized by depleted NPC and increased CPC, which is dominated by CD8+ T cells. Furthermore, CPC from CEN and CO share enhanced signaling pathways and transcriptional factors associated with immune response, and possesse similar T-cell-receptor features, such as high clonal expansion. Interestingly, rather than a significant increase in GZMK+ CD8 cells during aging, centenarians show accumulation of GZMB+ and CMC1+ CD8 T cells. Collectively, this study unveils an immune remodeling pattern reflected by both quantitative increase and functional reinforcement of cytotoxic T cells which are essential for healthy aging.

14.
ACS Nano ; 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36354967

RESUMO

Neurotoxins attack and destruct the nervous system, which can cause serious health problems and security threats. Existing detoxification approaches, such as antibodies and small molecule antidotes, rely on neurotoxin's molecular structure as design cues and require toxin-specific development for each type of toxins. However, the enormous diversity of neurotoxins makes such structure-based development of antitoxin particularly challenging and inefficient. Here, we report on the development and use of neuronal membrane-coated nanosponges (denoted "Neuron-NS") as an effective approach to detoxifying neurotoxins. Specifically, Neuron-NS act as neuron decoys to lure neurotoxins, bind with and neutralize the toxins, and thus block them from attacking the host neuron cells. These nanosponges detoxify neurotoxins regardless of their molecular structures and therefore can overcome the challenge posed by toxin structural diversity. In the study, we fabricate Neuron-NS by coating the membrane of Neuro-2a cells onto polymeric cores. Meanwhile, we select tetrodotoxin (TTX) as a model neurotoxin and demonstrate the detoxification efficacy of the Neuron-NS in a cytotoxicity assay, a calcium flux assay, and a cell osmotic swelling assay in vitro. Additionally, in mouse models of TTX intoxication, the Neuron-NS significantly enhance mouse survival in therapeutic and prophylactic regimens without showing acute toxicity. Overall, the Neuron-NS contribute to the current detoxification arsenal with the potential to treat various injuries and diseases caused by neurotoxins.

15.
Plant Cell Rep ; 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36348065

RESUMO

KEY MESSAGE: Inoculation of wheat seedling with Bacillus sp. wp-6 changed amino acid metabolism and flavonoid synthesis and promoted plant growth. Plant growth-promoting rhizobacteria (PGPR), which can reduce the use of agrochemicals, is vital for the development of sustainable agriculture. In this study, proteomics and metabolomics analyses were performed to investigate the effects of inoculation with a PGPR, Bacillus sp. wp-6, on wheat (Triticum aestivum L.) seedling growth. The results showed that inoculation with Bacillus sp. wp-6 increased shoot and root fresh weights by 19% and 18%, respectively, after 40 days. The expression levels of alpha-linolenic acid metabolism-related proteins and metabolites (lipoxygenase 2, allene oxide synthase 2, jasmonic acid, 17-hydroxylinolenic acid) and flavonoid biosynthesis-related proteins and metabolites (chalcone synthase 2 and PHC 4'-O-glucoside) were up-regulated. In addition, the expression levels of amino acid metabolism-related proteins (NADH-dependent glutamate synthase, bifunctional aspartokinase/homoserine, anthranilate synthase alpha subunit 1, and 3-phosphoshikimate 1-carboxyvinyltransferase) and metabolites (L-aspartate, L-arginine, and S-glutathionyl-L-cysteine) were also significantly up-regulated. Among them, NADH-dependent glutamate synthase and bifunctional aspartokinase/homoserine could act as regulators of nitrogen metabolism. Overall, inoculation of wheat with Bacillus sp. wp-6 altered alpha-linolenic acid metabolism, amino acid metabolism, and flavonoid synthesis and promoted wheat seedling growth. This study will deepen our understanding of the mechanism by which Bacillus sp. wp-6 promotes wheat growth using proteomics and metabolomics.

16.
Microb Ecol ; 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36372840

RESUMO

Fungal communities are essential to the maintenance of soil multifunctionality. Plant invasion represents a growing challenge for the conservation of soil biodiversity across the globe, but the impact of non-native species invasion on fungal diversity, community structure, and assembly processes remains largely unknown. Here, we examined the diversity, community composition, functional guilds, and assembly process of fungi at three soil depths underneath a native species, three non-native species, and a bare tidal flat from a coastal wetland. Plant species was more important than soil depth in regulating the diversity, community structure, and functional groups of fungi. Non-native species, especially Spartina alterniflora, increased fungal diversity, altered fungal community structure, and increased the relative abundance of saprotrophic and pathogenic fungi in coastal wetland soils. Stochastic processes played a predominant role in driving fungal community assembly, explaining more than 70% of the relative contributions. However, compared to a native species, non-native species, especially S. alterniflora, reduced the relative influence of stochastic processes in fungal community assembly. Collectively, our results provide novel evidence that non-native species can increase fungal diversity, the relative abundance of saprotrophic and pathogenic fungi, and deterministic processes in the assembly of fungi in coastal wetlands, which can expand our knowledge of the dynamics of fungal communities in subtropical coastal wetlands.

17.
Am J Epidemiol ; 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36345076

RESUMO

We aimed to assess the associations of peripheral neuropathy (PN) with vision and hearing impairment among adults aged ≥40 years who attended the lower extremity disease exam for the National Health and Nutrition Examination Survey (NHANES) 1999-2004. Overall, 11.8±0.5% of adults had diabetes, 13.2±0.5% had PN (26.6±1.4% with diabetes, 11.4±0.5% without diabetes), 1.6±0.1% had vision impairment, and 15.4± 1.1% had hearing impairment. The prevalence of vision impairment was 3.89% (95%CI 2.99-5.05) among adults with PN and 1.29% (95%CI 1.04-1.60) among adults without PN (P<0.001). After adjustment, PN was associated with vision impairment overall (OR 1.48, 95%CI 1.03-2.13) and among adults without diabetes (OR 1.80, 95%CI 1.17-2.77), but not among adults with diabetes (P-for-interaction=0.018). The prevalence of hearing impairment was 26.5% (95%CI 20.4-33.7) among adults with PN and 14.2% (95%CI 12.4-16.3) among adults without PN (P<0.001). The association of PN with any hearing impairment was not significant after adjustment (OR 1.24, 95%CI 0.86-1.77). However, the association of PN with moderate/severe hearing impairment was significant overall (OR 2.55, 95%CI 1.40-4.64) and among adults without diabetes (OR 3.26, 95%CI 1.80-5.91). Overall, these findings suggest an association between peripheral and audiovisual sensory impairment that is unrelated to diabetes.

18.
PLoS Biol ; 20(11): e3001856, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36318514

RESUMO

Feingold syndrome type 1, caused by loss-of-function of MYCN, is characterized by varied phenotypes including esophageal and duodenal atresia. However, no adequate model exists for studying the syndrome's pathological or molecular mechanisms, nor is there a treatment strategy. Here, we developed a zebrafish Feingold syndrome type 1 model with nonfunctional mycn, which had severe intestinal atresia. Single-cell RNA-seq identified a subcluster of intestinal cells that were highly sensitive to Mycn, and impaired cell proliferation decreased the overall number of intestinal cells in the mycn mutant fish. Bulk RNA-seq and metabolomic analysis showed that expression of ribosomal genes was down-regulated and that amino acid metabolism was abnormal. Northern blot and ribosomal profiling analysis showed abnormal rRNA processing and decreases in free 40S, 60S, and 80S ribosome particles, which led to impaired translation in the mutant. Besides, both Ribo-seq and western blot analysis showed that mTOR pathway was impaired in mycn mutant, and blocking mTOR pathway by rapamycin treatment can mimic the intestinal defect, and both L-leucine and Rheb, which can elevate translation via activating TOR pathway, could rescue the intestinal phenotype of mycn mutant. In summary, by this zebrafish Feingold syndrome type 1 model, we found that disturbance of ribosomal biogenesis and blockage of protein synthesis during development are primary causes of the intestinal defect in Feingold syndrome type 1. Importantly, our work suggests that leucine supplementation may be a feasible and easy treatment option for this disease.


Assuntos
Microcefalia , Peixe-Zebra , Animais , Proteína Proto-Oncogênica N-Myc , Peixe-Zebra/metabolismo , Microcefalia/genética , Serina-Treonina Quinases TOR/metabolismo , Leucina
20.
Chin Med J (Engl) ; 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36385099

RESUMO

ABSTRACT: Tumor-associated macrophages (TAMs) are an essential proportion of tumor-infiltrating immune cells in the tumor microenvironment (TME) and have immunosuppressive functions. The high plasticity and corresponding phenotypic transformation of TAMs facilitate oncogenesis and progression, and suppress antineoplastic responses. Due to the uncontrolled proliferation of tumor cells, metabolism homeostasis is regulated, leading to a series of alterations in the metabolite profiles in the TME, which have a commensurate influence on immune cells. Metabolic reprogramming of the TME has a profound impact on the polarization and function of TAMs, and can alter their metabolic profiles. TAMs undergo a series of metabolic reprogramming processes, involving glucose, lipid, and amino acid metabolism, and other metabolic pathways, which terminally promote the development of the immunosuppressive phenotype. TAMs express a pro-tumor phenotype by increasing glycolysis, fatty acid oxidation, cholesterol efflux, and arginine, tryptophan, glutamate, and glutamine metabolism. Previous studies on the metabolism of TAMs demonstrated that metabolic reprogramming has intimate crosstalk with anti-tumor or pro-tumor phenotypes and is crucial for the function of TAMs themselves. Targeting metabolism-related pathways is emerging as a promising therapeutic modality because of the massive metabolic remodeling that occurs in malignant cells and TAMs. Evidence reveals that the efficacy of immune checkpoint inhibitors is improved when combined with therapeutic strategies targeting metabolism-related pathways. In-depth research on metabolic reprogramming and potential therapeutic targets provides more options for anti-tumor treatment and creates new directions for the development of new immunotherapy methods. In this review, we elucidate the metabolic reprogramming of TAMs and explore how they sustain immunosuppressive phenotypes to provide a perspective for potential metabolic therapies.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...