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1.
PLoS One ; 19(8): e0307293, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39106249

RESUMO

A new process of continuous and synchronous calibration process of ovality and straightness for LSAW (Longitudinally Submerged Arc Welding, LSAW) pipes with three rollers is proposed. Specifically, the process is introduced from three aspects: roller-shape, loading parameters and axial and circumferential deformation paths. The process is verified by numerical simulation and physical experiments. Further, the stress-strain in the Sections Ⅱ and Ⅳ is analyzed. The relationship between the process parameters and the residual ovality and residual straightness by experiments is discussed. The calibration scheme of LSAW pipes is put forward by using the control variable method. The results show that the shear stress is the principal stress direction in the Sections Ⅱ and Ⅳ. The residual ovality and residual straightness decrease with the increase of the radial reduction and times of reciprocating bending. The reciprocating bending process can eliminate the difference of the initial curvature, make the curvature of each section tend to be uniform. After calibration, the residual straightness is less than 0.2% and the residual ovality is less than 1%, demonstrating a good feasibility of this process.


Assuntos
Soldagem , Calibragem , Soldagem/métodos , Estresse Mecânico , Desenho de Equipamento
2.
Artigo em Inglês | MEDLINE | ID: mdl-39090509

RESUMO

Phonetic processing, whereby the bottom-up speech signal is translated into higher-level phonological representations such as phonemes, has been demonstrated to be influenced by phonological lexical neighborhoods. Previous studies show facilitatory effects of lexicality and phonological neighborhood density on phonetic categorization. However, given the evidence for lexical competition in spoken word recognition, we hypothesize that there are concurrent facilitatory and inhibitory effects of phonological lexical neighborhoods on phonetic processing. In Experiments 1 and 2, participants categorized the onset phoneme in word-nonword and nonword-word acoustic continua. The results show that the target word of the continuum exhibits facilitatory lexical influences whereas rhyme neighbors inhibit phonetic categorization. The results support the hypothesis that sublexical phonetic processing is affected by multiple facilitatory and inhibitory lexical forces in the processing stream.

3.
Microorganisms ; 12(7)2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-39065120

RESUMO

Many studies have attempted to explore the changes in the structure and function of symbiotic microbiomes, as well as the underlying genetic mechanism during crop domestication. However, most of these studies have focused on crop root microbiomes, while those on leaf and fruit are rare. In this study, we generated a comprehensive dataset including the metagenomic (leaf) and metatranscriptomic (fruit pericarp in the orange stage) data of hundreds of germplasms from three tomato clades: Solanum pimpinellifolium (PIM), cherry tomato (S. lycopersicum var. cerasiforme) (CER), and S. lycopersicum group (BIG). We investigated the effect of domestication and improvement processes on the structure of the symbiotic microbiome of tomato leaf and fruit pericarp, as well as its genetic basis. We were able to obtain the composition of the symbiotic microbiome of tomato leaf and fruit pericarp, based on which the tomato clade (PIM, CER, or BIG) was predicted with high accuracy through machine learning methods. In the processes of tomato domestication and improvement, changes were observed in the relative abundance of specific bacterial taxa, Bacillus for example, in the tomato leaf and fruit pericarp symbiotic microbiomes, as well as in the function of these symbiotic microbiomes. In addition, SNP loci that were significantly associated with microbial species that are characteristic of tomato leaf were identified. Our results show that domestication and genetic improvement processes alter the symbiotic microbiome structure and function of tomato leaf and fruit pericarp. We propose that leaf and fruit microbiomes are more suitable for revealing changes in symbiotic microbiomes during the domestication process and the underlying genetic basis for these changes due to the exclusion of the influence of environmental factors such as soil types on the microbiome structure.

5.
Curr Protoc ; 4(7): e1038, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38967962

RESUMO

A variety of metals, e.g., lead (Pb), cadmium (Cd), and lithium (Li), are in the environment and are toxic to humans. Hematopoietic stem cells (HSCs) reside at the apex of hematopoiesis and are capable of generating all kinds of blood cells and self-renew to maintain the HSC pool. HSCs are sensitive to environmental stimuli. Metals may influence the function of HSCs by directly acting on HSCs or indirectly by affecting the surrounding microenvironment for HSCs in the bone marrow (BM) or niche, including cellular and extracellular components. Investigating the impact of direct and/or indirect actions of metals on HSCs contributes to the understanding of immunological and hematopoietic toxicology of metals. Treatment of HSCs with metals ex vivo, and the ensuing HSC transplantation assays, are useful for evaluating the impacts of the direct actions of metals on the function of HSCs. Investigating the mechanisms involved, given the rarity of HSCs, methods that require large numbers of cells are not suitable for signal screening; however, flow cytometry is a useful tool for signal screening HSCs. After targeting signaling pathways, interventions ex vivo and HSCs transplantation are required to confirm the roles of the signaling pathways in regulating the function of HSCs exposed to metals. Here, we describe protocols to evaluate the mechanisms of direct and indirect action of metals on HSCs. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Identify the impact of a metal on the competence of HSCs Basic Protocol 2: Identify the impact of a metal on the lineage bias of HSC differentiation Basic Protocol 3: Screen the potential signaling molecules in HSCs during metal exposure Alternate Protocol 1: Ex vivo treatment with a metal on purified HSCs Alternate Protocol 2: Ex vivo intervention of the signaling pathway regulating the function of HSCs during metal exposure.


Assuntos
Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/citologia , Animais , Metais/toxicidade , Camundongos , Humanos , Transplante de Células-Tronco Hematopoéticas , Citometria de Fluxo/métodos
6.
Environ Sci Technol ; 58(28): 12356-12367, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38953388

RESUMO

Unhealthy lifestyles, obesity, and environmental pollutants are strongly correlated with the development of nonalcoholic fatty liver disease (NAFLD). Haloacetaldehyde-associated disinfection byproducts (HAL-DBPs) at various multiples of concentrations found in finished drinking water together with high-fat (HF) were examined to gauge their mixed effects on hepatic lipid metabolism. Using new alternative methods (NAMs), studying effects in human cells in vitro for risk assessment, we investigated the combined effects of HF and HAL-DBPs on hepatic lipid metabolism and lipotoxicity in immortalized LO-2 human hepatocytes. Coexposure of HAL-DBPs at various multiples of environmental exposure levels with HF increased the levels of triglycerides, interfered with de novo lipogenesis, enhanced fatty acid oxidation, and inhibited the secretion of very low-density lipoproteins. Lipid accumulation caused by the coexposure of HAL-DBPs and HF also resulted in more severe lipotoxicity in these cells. Our results using an in vitro NAM-based method provide novel insights into metabolic reprogramming in hepatocytes due to coexposure of HF and HAL-DBPs and strongly suggest that the risk of NAFLD in sensitive populations due to HAL-DBPs and poor lifestyle deserves further investigation both with laboratory and epidemiological tools. We also discuss how results from our studies could be used in health risk assessments for HAL-DBPs.


Assuntos
Hepatócitos , Metabolismo dos Lipídeos , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Desinfecção , Fígado/metabolismo , Fígado/efeitos dos fármacos , Acetaldeído/toxicidade , Linhagem Celular
7.
Colloids Surf B Biointerfaces ; 240: 113970, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38788474

RESUMO

Extracts of traditional Chinese herbs (TCH) contain a variety of anti-allergic, anti-inflammatory and other bioactive factors. However, the defect of easy degradation or loss of active ingredients limits its application in traditional Chinese medicines (TCM) loaded textiles. In this work, TCH extracts containing different active ingredients were innovatively proposed as the core material of microcapsules. The feasibility of microencapsulation of multi-component TCH extracts in the essential oil state was initially demonstrated. Polyacrylate was also used as a binder to load the microcapsules onto the fabric to improve the durability and wash resistance of the treated fabric. Modeling the oil release of microcapsules for controlled release under different conditions may provide new possible uses for the materials. Results show that the constructed microcapsule has a smooth surface without depression and can be continuously released for over 30 days. The release behavior of microcapsules follows different release mechanisms and can be modulated by temperature and water molecules. The incorporation of microcapsules and polyacrylate does not significantly change the fabric's air permeability, water vapor transmission and hydrophilicity. The washing durability and friction properties of the microcapsule-based fabric are greatly improved, and it can withstand 30 washing tests and 200 friction tests. Moreover, the results of methyl thiazolyl tetrazolium (MTT) release assay using human dermal papilla cells (HDP) as an in vitro template confirm that the microcapsule has no toxic effects on human cells. Therefore, the successful microencapsulation of multi-component TCH extracts indicates their potential application in the field of TCM-loaded textiles.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Têxteis , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Composição de Medicamentos/métodos , Cápsulas/química , Sobrevivência Celular/efeitos dos fármacos
8.
BMC Surg ; 24(1): 170, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811935

RESUMO

OBJECTIVE: To investigate whether simethicone expediates the remission of abdominal distension after laparoscopic cholecystectomy (LC). METHODS: This retrospective study involved LC patients who either received perioperative simethicone treatment or not. Propensity score matching (PSM) was employed to minimize bias. The primary endpoint was the remission rate of abdominal distension within 24 h after LC. Univariable and multivariable logistic regression analyses were conducted to identify independent risk factors affecting the early remission of abdominal distension after LC. Subsequently, a prediction model was established and validated. RESULTS: A total of 1,286 patients were divided into simethicone (n = 811) and non-simethicone groups (n = 475) as 2:1 PSM. The patients receiving simethicone had better remission rates of abdominal distension at both 24 h and 48 h after LC (49.2% vs. 34.7%, 83.9% vs. 74.8%, respectively), along with shorter time to the first flatus (14.6 ± 11.1 h vs. 17.2 ± 9.1 h, P < 0.001) compared to those without. Multiple logistic regression identified gallstone (OR = 0.33, P = 0.001), cholecystic polyp (OR = 0.53, P = 0.050), preoperative abdominal distention (OR = 0.63, P = 0.002) and simethicone use (OR = 1.89, P < 0.001) as independent factors contributing to the early remission of abdominal distension following LC. The prognosis model developed for predicting remission rates of abdominal distension within 24 h after LC yielded an area under the curve of 0.643 and internal validation a value of 0.644. CONCLUSIONS: Simethicone administration significantly enhanced the early remission of post-LC abdominal distension, particularly for patients who had gallstones, cholecystic polyp, prolonged anesthesia or preoperative abdominal distention. TRIAL REGISTRATION: ChiCTR2200064964 (24/10/2022).


Assuntos
Colecistectomia Laparoscópica , Complicações Pós-Operatórias , Pontuação de Propensão , Simeticone , Humanos , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Simeticone/uso terapêutico , Simeticone/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Adulto , Resultado do Tratamento , Idoso , Abdome/cirurgia
9.
Inflamm Res ; 73(6): 961-978, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38587531

RESUMO

BACKGROUND: Atherosclerosis is a chronic inflammatory disease characterized by abnormal lipid deposition in the arteries. Programmed cell death is involved in the inflammatory response of atherosclerosis, but PANoptosis, as a new form of programmed cell death, is still unclear in atherosclerosis. This study explored the key PANoptosis-related genes involved in atherosclerosis and their potential mechanisms through bioinformatics analysis. METHODS: We evaluated differentially expressed genes (DEGs) and immune infiltration landscape in atherosclerosis using microarray datasets and bioinformatics analysis. By intersecting PANoptosis-related genes from the GeneCards database with DEGs, we obtained a set of PANoptosis-related genes in atherosclerosis (PANoDEGs). Functional enrichment analysis of PANoDEGs was performed and protein-protein interaction (PPI) network of PANoDEGs was established. The machine learning algorithms were used to identify the key PANoDEGs closely linked to atherosclerosis. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic potency of key PANoDEGs. CIBERSORT was used to analyze the immune infiltration patterns in atherosclerosis, and the Spearman method was used to study the relationship between key PANoDEGs and immune infiltration abundance. The single gene enrichment analysis of key PANoDEGs was investigated by GSEA. The transcription factors and target miRNAs of key PANoDEGs were predicted by Cytoscape and online database, respectively. The expression of key PANoDEGs was validated through animal and cell experiments. RESULTS: PANoDEGs in atherosclerosis were significantly enriched in apoptotic process, pyroptosis, necroptosis, cytosolic DNA-sensing pathway, NOD-like receptor signaling pathway, lipid and atherosclerosis. Four key PANoDEGs (ZBP1, SNHG6, DNM1L, and AIM2) were found to be closely related to atherosclerosis. The ROC curve analysis demonstrated that the key PANoDEGs had a strong diagnostic potential in distinguishing atherosclerotic samples from control samples. Immune cell infiltration analysis revealed that the proportion of initial B cells, plasma cells, CD4 memory resting T cells, and M1 macrophages was significantly higher in atherosclerotic tissues compared to normal tissues. Spearman analysis showed that key PANoDEGs showed strong correlations with immune cells such as T cells, macrophages, plasma cells, and mast cells. The regulatory networks of the four key PANoDEGs were established. The expression of key PANoDEGs was verified in further cell and animal experiments. CONCLUSIONS: This study evaluated the expression changes of PANoptosis-related genes in atherosclerosis, providing a reference direction for the study of PANoptosis in atherosclerosis and offering potential new avenues for further understanding the pathogenesis and treatment strategies of atherosclerosis.


Assuntos
Aterosclerose , Perfilação da Expressão Gênica , Aterosclerose/genética , Aterosclerose/imunologia , Animais , Mapas de Interação de Proteínas/genética , Transcriptoma , Humanos , Biologia Computacional , Masculino , Piroptose/genética , Camundongos
11.
Pharmaceuticals (Basel) ; 17(3)2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38543064

RESUMO

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal and chronic interstitial lung disease. Intricate pathogenesis of pulmonary fibrosis and only two approved medications with side effects and high cost bring us the challenge of fully understanding this lethal disease and urgency to find more safe and low-cost therapeutic alternatives. PURPOSE: Demethyleneberberine (DMB) has been demonstrated to have various anti-inflammatory, antioxidant, antifibrosis and anti-cancer bioactivities. The objective of this study was to evaluate the effect of DMB on pulmonary fibrosis and investigate the mechanism. METHODS: Bleomycin (BLM)-induced pulmonary fibrosis was established in mice to evaluate the antifibrotic effect of DMB in vivo. A549 and MRC5 cells were used to evaluate the effect of DMB on epithelial-mesenchymal transition (EMT) and fibroblast-myofibroblast transition (FMT) in vitro. High throughput sequencing, biotin-avidin system and site-directed mutagenesis were applied to explore the mechanism of DMB in alleviating pulmonary fibrosis. RESULTS: DMB alleviated BLM-induced pulmonary fibrosis in vivo by improving the survival state of mice, significantly reducing pulmonary collagen deposition and oxidative stress and improving lung tissue morphology. Meanwhile, DMB was demonstrated to inhibit epithelial-mesenchymal transition (EMT) and fibroblast-myofibroblast transition (FMT) in vitro. High throughput sequencing analysis indicated that GREM1, a highly upregulated profibrotic mediator in IPF and BLM-induced pulmonary fibrosis, was significantly downregulated by DMB. Furthermore, USP11 was revealed to be involved in the deubiquitination of GREM1 in this study and DMB promoted the ubiquitination and degradation of GREM1 by inhibiting USP11. Remarkably, DMB was demonstrated to selectively bind to the Met776 residue of USP11, leading to disruption of USP11 deubiquitinating GREM1. In addition, DMB presented an equivalent antifibrotic effect at a lower dose compared with pirfenidone and showed no obvious toxicity or side effects. CONCLUSIONS: This study revealed that USP11/GREM1 could be a potential target for IPF management and identified that DMB could promote GREM1 degradation by inhibiting USP11, thereby alleviating pulmonary fibrosis.

12.
Int J Biochem Cell Biol ; 169: 106539, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38290690

RESUMO

Doxorubicin (DOX), a widely used chemotherapy agent in cancer treatment, encounters limitations in clinical efficacy due to associated cardiotoxicity. This study aims to explore the role of AKT serine/threonine kinase 2 (AKT2) in mitigating DOX-induced oxidative stress within the heart through both intracellular and extracellular signaling pathways. Utilizing Akt2 knockout (KO) and Nrf2 KO murine models, alongside neonatal rat cardiomyocytes (NRCMs), we systematically investigate the impact of AKT2 deficiency on DOX-induced cardiac injury. Our findings reveal that DOX administration induces significant oxidative stress, a primary contributor to cardiac injury. Importantly, Akt2 deficiency exhibits a protective effect by alleviating DOX-induced oxidative stress. Mechanistically, Akt2 deficiency facilitates nuclear translocation of NRF2, thereby suppressing intracellular oxidative stress by promoting the expression of antioxidant genes. Furthermore, We also observed that AKT2 inhibition facilitates superoxide dismutase 2 (SOD2) expression both inside macrophages and SOD2 secretion to the extracellular matrix, which is involved in lowering oxidative stress in cardiomyocytes upon DOX stimulation. The present study underscores the important role of AKT2 in mitigating DOX-induced oxidative stress through both intracellular and extracellular signaling pathways. Additionally, our findings propose promising therapeutic strategies for addressing DOX-induced cardiomyopathy in clinic.


Assuntos
Miócitos Cardíacos , Fator 2 Relacionado a NF-E2 , Ratos , Camundongos , Animais , Miócitos Cardíacos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Doxorrubicina/efeitos adversos , Estresse Oxidativo , Cardiotoxicidade/tratamento farmacológico , Cardiotoxicidade/metabolismo , Apoptose
13.
Life Sci ; 341: 122474, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38296191

RESUMO

AIMS: This work sought to investigate the mechanism underlying the STING signaling pathway during myocardial infarction (MI), and explore the involvement and the role of SIRT6 in the process. MAIN METHODS: Mice underwent the surgery of permanent left anterior descending (LAD) artery constriction. Primary cardiomyocytes (CMs) and fibroblasts were subjected to hypoxia to mimic MI in vitro. STING expression was assessed in the infarct heart, and the effect of STING inhibition on cardiac fibrosis was explored. This study also evaluated the regulatory effect of STING by SIRT6 in macrophages. KEY FINDINGS: STING protein was increased in the infarct heart tissue, highlighting its involvement in the post-MI inflammatory response. Hypoxia-induced death of CMs and fibroblasts contributed to the upregulation of STING in macrophages, establishing the involvement of STING in the intercellular signaling during MI. Inhibition of STING resulted in a significant reduction of cardiac fibrosis at day 14 after MI. Additionally, this study identified SIRT6 as a key regulator of STING via influencing its acetylation and ubiquitination in macrophages, providing novel insights into the posttranscriptional modification and expression of STING at the acute phase after myocardial infarction. SIGNIFICANCE: This work shows the key role of SIRT6/STING signaling in the pathogenesis of cardiac injury after MI, suggesting that targeting this regulatory pathway could be a promising strategy to attenuate cardiac fibrosis after MI.


Assuntos
Traumatismos Cardíacos , Infarto do Miocárdio , Sirtuínas , Animais , Camundongos , Modelos Animais de Doenças , Fibrose , Traumatismos Cardíacos/metabolismo , Hipóxia/metabolismo , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Transdução de Sinais , Sirtuínas/metabolismo
15.
Proc Natl Acad Sci U S A ; 120(51): e2303075120, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38100414

RESUMO

Adipose tissue macrophages (ATM) are key players in the development of obesity and associated metabolic inflammation which contributes to systemic metabolic dysfunction. We here found that fibroblast activation protein α (FAP), a well-known marker of cancer-associated fibroblast, is selectively expressed in murine and human ATM among adipose tissue-infiltrating leukocytes. Macrophage FAP deficiency protects mice against diet-induced obesity and proinflammatory macrophage infiltration in obese adipose tissues, thereby alleviating hepatic steatosis and insulin resistance. Mechanistically, FAP specifically mediates monocyte chemokine protein CCL8 expression by ATM, which is further upregulated upon high-fat-diet (HFD) feeding, contributing to the recruitment of monocyte-derived proinflammatory macrophages with no effect on their classical inflammatory activation. CCL8 overexpression restores HFD-induced metabolic phenotypes in the absence of FAP. Moreover, macrophage FAP deficiency enhances energy expenditure and oxygen consumption preceding differential body weight after HFD feeding. Such enhanced energy expenditure is associated with increased levels of norepinephrine (NE) and lipolysis in white adipose tissues, likely due to decreased expression of monoamine oxidase, a NE degradation enzyme, by Fap-/- ATM. Collectively, our study identifies FAP as a previously unrecognized regulator of ATM function contributing to diet-induced obesity and metabolic inflammation and suggests FAP as a potential immunotherapeutic target against metabolic disorders.


Assuntos
Tecido Adiposo , Resistência à Insulina , Animais , Humanos , Camundongos , Tecido Adiposo/metabolismo , Dieta Hiperlipídica , Inflamação/metabolismo , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Obesidade/metabolismo
16.
Heliyon ; 9(12): e23186, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38149204

RESUMO

Although much research has focused on AlSi10Mg processed via laser-based powder bed fusion, the material deformation mechanisms at the microscale are still unclear. To improve the current understanding, 3D measurements of the strain field at the microstructural scale are needed to complement surface-based SEM observations. This work demonstrates that X-ray tomography combined with digital volume correlation can be used to measure the strain in the bulk of AlSi10Mg using the Si-rich particles contained in the heat-treated microstructure as markers. The method allows for measuring strains larger than 0.5 % with a spatial resolution of 35 µm and it can thus be used to study the impact of factors like porosity distribution or crystallographic texture on the material deformation and damage mechanisms.

17.
Opt Express ; 31(23): 38840-38853, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-38017978

RESUMO

Novel focusing optics composed of twin paraboloidal capillaries coated with Pt, for laboratory X-ray sources are presented and characterized. The optics are designed to focus the X-rays, resulting in an achromatic focused beam with photon energies up to 40 keV. The performance of the optics under different operational conditions is studied by comparing the energy-photon count spectra of the direct and focused beams. Based on these analyses, the optics gain and efficiency as a function of photon energy are determined. A focal spot of 8.5 µm with a divergence angle of 0.59° is observed. The obtained characteristics are discussed and related to theoretical considerations. Moreover, the suitability and advantages of the present optics for X-ray microdiffraction is demonstrated using polycrystalline aluminium. Finally, possibilities for further developments are suggested.

18.
Food Chem Toxicol ; 181: 114081, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37783420

RESUMO

Lithium (Li) has been widely used in clinical therapy and new Li-ion battery industry. To date, the impact of Li on the development of immune cells is largely unknown. The aim of this study was to investigate the impact of Li on hematopoiesis. C57BL/6 (B6) mice were treated with 50 ppm LiCl, 200 ppm LiCl, or the control via drinking water for 3 months, and thereafter the hematopoiesis was evaluated. Treatment with Li increased the number of mature lymphoid cells while suppressing the number of mature myeloid cells in mice. In addition, a direct action of Li on hematopoietic stem cells (HSC) suppressed endoplasmic reticulum (ER) stress to reduce the proliferation of HSC in the bone marrow (BM), thus leading to fewer HSC in mice. On the other hand, the suppression of ER stress by Li exposure increased the expression of Hsp90, which promoted the potential of lymphopoiesis but did not impact that for myelopoiesis in HSC in the BM of mice. Moreover, in vitro treatment with Li also likely disturbed the ER stress-Hsp90 signaling, suppressed the proliferation, and increased the potential for lymphopoiesis in human HSC. Our study reveals a previously unrecognized toxicity of Li on HSC and may advance our understanding for the immunotoxicology of Li.


Assuntos
Células-Tronco Hematopoéticas , Lítio , Animais , Humanos , Camundongos , Medula Óssea , Hematopoese , Células-Tronco Hematopoéticas/metabolismo , Lítio/toxicidade , Camundongos Endogâmicos C57BL
19.
JAMA Intern Med ; 183(12): 1389-1390, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37843852

RESUMO

This case report describes a man in his 30s who presented to the emergency department with a sudden onset of distal extremity weakness after waking up 10 hours prior.


Assuntos
Eletrocardiografia , Debilidade Muscular , Masculino , Humanos , Debilidade Muscular/diagnóstico , Debilidade Muscular/etiologia , Extremidades
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